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Gene Information

Gene symbol: KCNJ11

Gene name: potassium inwardly-rectifying channel, subfamily J, member 11

HGNC ID: 6257

Synonyms: Kir6.2, BIR

Related Genes

#	Gene Symbol	Number of hits
1	ABCC1	1 hits
2	ABCC8	1 hits
3	ABCC9	1 hits
4	ADAMTS9	1 hits
5	ADIPOQ	1 hits
6	ADRA2A	1 hits
7	AK1	1 hits
8	APOB	1 hits
9	ARC	1 hits
10	ARHGEF11	1 hits
11	BCL11A	1 hits
12	CACNA1D	1 hits
13	CAMK1D	1 hits
14	CAPN10	1 hits
15	CAST	1 hits
16	CAV1	1 hits
17	CBX4	1 hits
18	CD38	1 hits
19	CD9	1 hits
20	CDC123	1 hits
21	CDKAL1	1 hits
22	CDKN2A	1 hits
23	CDKN2B	1 hits
24	CFH	1 hits
25	CLCNKB	1 hits
26	CNBP	1 hits
27	CPT2	1 hits
28	CTNS	1 hits
29	EIF2AK3	1 hits
30	ENPP1	1 hits
31	EXOSC4	1 hits
32	FFAR1	1 hits
33	FOXA2	1 hits
34	FOXP3	1 hits
35	FTO	1 hits
36	G6PC2	1 hits
37	GAPDH	1 hits
38	GATA4	1 hits
39	GCG	1 hits
40	GCK	1 hits
41	GCKR	1 hits
42	GEM	1 hits
43	GHR	1 hits
44	GIP	1 hits
45	GIPR	1 hits
46	GJA1	1 hits
47	GLUD1	1 hits
48	GNAI2	1 hits
49	GSTA1	1 hits
50	GYS1	1 hits
51	HADH	1 hits
52	HHEX	1 hits
53	HK1	1 hits
54	HK2	1 hits
55	HMX1	1 hits
56	HNF1A	1 hits
57	HNF1B	1 hits
58	HNF4A	1 hits
59	IAPP	1 hits
60	IDE	1 hits
61	IGF1	1 hits
62	IGF2	1 hits
63	IGF2BP2	1 hits
64	IKBKAP	1 hits
65	INS	1 hits
66	INSM1	1 hits
67	INSR	1 hits
68	IRS1	1 hits
69	ISL1	1 hits
70	JAZF1	1 hits
71	KCNB1	1 hits
72	KCNE2	1 hits
73	KCNJ1	1 hits
74	KCNJ2	1 hits
75	KCNJ3	1 hits
76	KCNJ5	1 hits
77	KCNJ8	1 hits
78	KCNQ1	1 hits
79	KIR3DL1	1 hits
80	KLF7	1 hits
81	KLRG1	1 hits
82	LGR5	1 hits
83	LIPC	1 hits
84	LPL	1 hits
85	MAPK1	1 hits
86	MAPK6	1 hits
87	MED23	1 hits
88	MLXIPL	1 hits
89	MNX1	1 hits
90	NEUROD1	1 hits
91	NEUROG3	1 hits
92	NKX2-2	1 hits
93	NKX6-1	1 hits
94	NKX6-2	1 hits
95	NOTCH2	1 hits
96	NPPA	1 hits
97	NPY	1 hits
98	NR0B2	1 hits
99	ONECUT1	1 hits
100	P2RY2	1 hits
101	PAX4	1 hits
102	PAX6	1 hits
103	PC	1 hits
104	PCSK1	1 hits
105	PCSK2	1 hits
106	PDX1	1 hits
107	PEA15	1 hits
108	POMC	1 hits
109	PON2	1 hits
110	POU2F1	1 hits
111	POU2F2	1 hits
112	PPARA	1 hits
113	PPARG	1 hits
114	PPBP	1 hits
115	PPP3CB	1 hits
116	PRKCZ	1 hits
117	PTF1A	1 hits
118	PYY	1 hits
119	RALGPS2	1 hits
120	RHOD	1 hits
121	SCN2A	1 hits
122	SERPINE1	1 hits
123	SLC16A1	1 hits
124	SLC2A1	1 hits
125	SLC2A2	1 hits
126	SLC30A8	1 hits
127	SLC4A1	1 hits
128	SNAP23	1 hits
129	SNAP25	1 hits
130	SP1	1 hits
131	SST	1 hits
132	STX1A	1 hits
133	STX7	1 hits
134	SUCLG1	1 hits
135	TCF7	1 hits
136	TCF7L2	1 hits
137	THADA	1 hits
138	TNF	1 hits
139	TRH	1 hits
140	TSPAN8	1 hits
141	UBQLNL	1 hits
142	UBXD5	1 hits
143	UCP2	1 hits
144	UHMK1	1 hits
145	USF1	1 hits
146	VWF	1 hits
147	WARS	1 hits
148	WFS1	1 hits
149	ZBED3	1 hits
150	ZFP57	1 hits
151	ZIC3	1 hits

Related Sentences

#	PMID	Sentence
1	8549873	Recent studies have shown that the beta-cell KATP channel comprises two subunits: a novel member of the inwardly rectifying K+ channel family, designated BIR and expressed at highest levels in pancreatic islets, and the sulfonylurea receptor (SUR).
2	8549873	The present study examined the contribution of the linked BIR and SUR genes to the development of NIDDM.
3	8549873	There was no evidence for linkage between these markers and NIDDM, suggesting that genetic variation in the BIR and SUR genes does not play a major role in susceptibility to NIDDM in Japanese.
4	8549873	Recent studies have shown that the beta-cell KATP channel comprises two subunits: a novel member of the inwardly rectifying K+ channel family, designated BIR and expressed at highest levels in pancreatic islets, and the sulfonylurea receptor (SUR).
5	8549873	The present study examined the contribution of the linked BIR and SUR genes to the development of NIDDM.
6	8549873	There was no evidence for linkage between these markers and NIDDM, suggesting that genetic variation in the BIR and SUR genes does not play a major role in susceptibility to NIDDM in Japanese.
7	8549873	Recent studies have shown that the beta-cell KATP channel comprises two subunits: a novel member of the inwardly rectifying K+ channel family, designated BIR and expressed at highest levels in pancreatic islets, and the sulfonylurea receptor (SUR).
8	8549873	The present study examined the contribution of the linked BIR and SUR genes to the development of NIDDM.
9	8549873	There was no evidence for linkage between these markers and NIDDM, suggesting that genetic variation in the BIR and SUR genes does not play a major role in susceptibility to NIDDM in Japanese.
10	8607800	The ATP-sensitive potassium channel of insulin-secreting pancreatic beta-cells is a complex of Kir6.2, a member of the inwardly rectifying potassium channel superfamily, and the sulfonylurea receptor.
11	8607800	Co-expression of rat Kir6.2 and sulfonylurea receptor in human embryonic kidney cells generated a potassium current with the properties of the beta-cell ATP-sensitive potassium channel.
12	8607800	A quantitative reverse transcriptase-polymerase chain reaction assay indicated that Kir6.2 and sulfonylurea receptor mRNAs were abundantly expressed in rat islets and that expression of Kir6.2 mRNA was reduced by >70% in islets from Zucker diabetic fatty male rats, whereas there was no significant change in sulfonylurea receptor mRNA levels.
13	8607800	The ATP-sensitive potassium channel of insulin-secreting pancreatic beta-cells is a complex of Kir6.2, a member of the inwardly rectifying potassium channel superfamily, and the sulfonylurea receptor.
14	8607800	Co-expression of rat Kir6.2 and sulfonylurea receptor in human embryonic kidney cells generated a potassium current with the properties of the beta-cell ATP-sensitive potassium channel.
15	8607800	A quantitative reverse transcriptase-polymerase chain reaction assay indicated that Kir6.2 and sulfonylurea receptor mRNAs were abundantly expressed in rat islets and that expression of Kir6.2 mRNA was reduced by >70% in islets from Zucker diabetic fatty male rats, whereas there was no significant change in sulfonylurea receptor mRNA levels.
16	8607800	The ATP-sensitive potassium channel of insulin-secreting pancreatic beta-cells is a complex of Kir6.2, a member of the inwardly rectifying potassium channel superfamily, and the sulfonylurea receptor.
17	8607800	Co-expression of rat Kir6.2 and sulfonylurea receptor in human embryonic kidney cells generated a potassium current with the properties of the beta-cell ATP-sensitive potassium channel.
18	8607800	A quantitative reverse transcriptase-polymerase chain reaction assay indicated that Kir6.2 and sulfonylurea receptor mRNAs were abundantly expressed in rat islets and that expression of Kir6.2 mRNA was reduced by >70% in islets from Zucker diabetic fatty male rats, whereas there was no significant change in sulfonylurea receptor mRNA levels.
19	8635661	The sulfonylurea receptor (SUR) gene, now known to encode an integral component of the pancreatic beta-cell ATP-sensitive potassium channel, IKATP, was investigated as a logical candidate for this disorder.
20	8635661	The two nucleotide-binding fold (NBF) regions of SUR are known to be critical for normal glucose regulation of insulin secretion.
21	8897013	We screened 135 white Caucasian patients with non-insulin-dependent diabetes mellitus (NIDDM) and 90 non-diabetic subjects for mutations in the Kir6.2 gene by single-stranded conformational polymorphism (SSCP) analysis.
22	8923011	Together, these mutations are associated with 88% of the HI chromosomes of the patients studied. 86Rb+ efflux measurements of COSm6 cells co-expressing Kir6.2 and either wild-type or delta F1388 SUR1 revealed that the F1388 mutation abolished ATP-sensitive potassium channel (KATP) activity in intact cells.
23	9032109	The cloning of the gene encoding the beta-cell inward rectifier Kir6.2 (Bir), a subunit of the beta-cell KATP channel, provided the opportunity to look for mutations in this gene that might contribute to the impaired insulin secretion of NIDDM.
24	9032109	Pairwise allelic associations indicated significant linkage disequilibrium between the variants in Kir6.2 and between them and a nearby pancreatic beta-cell sulfonylurea receptor (SUR1) missense variant (S1370A), but these linkage disequilibria did not differ between the NIDDM and control groups.
25	9032109	The results of these studies thus revealed that mutations in the coding region of Kir6.2 1) were not responsible for the previously noted association of the SUR1 variants with NIDDM (Inoue H et al., Diabetes 45:825-831, 1996) and 2) did not contribute to the impaired insulin secretion characteristic of NIDDM in Caucasian patients.
26	9032109	The cloning of the gene encoding the beta-cell inward rectifier Kir6.2 (Bir), a subunit of the beta-cell KATP channel, provided the opportunity to look for mutations in this gene that might contribute to the impaired insulin secretion of NIDDM.
27	9032109	Pairwise allelic associations indicated significant linkage disequilibrium between the variants in Kir6.2 and between them and a nearby pancreatic beta-cell sulfonylurea receptor (SUR1) missense variant (S1370A), but these linkage disequilibria did not differ between the NIDDM and control groups.
28	9032109	The results of these studies thus revealed that mutations in the coding region of Kir6.2 1) were not responsible for the previously noted association of the SUR1 variants with NIDDM (Inoue H et al., Diabetes 45:825-831, 1996) and 2) did not contribute to the impaired insulin secretion characteristic of NIDDM in Caucasian patients.
29	9032109	The cloning of the gene encoding the beta-cell inward rectifier Kir6.2 (Bir), a subunit of the beta-cell KATP channel, provided the opportunity to look for mutations in this gene that might contribute to the impaired insulin secretion of NIDDM.
30	9032109	Pairwise allelic associations indicated significant linkage disequilibrium between the variants in Kir6.2 and between them and a nearby pancreatic beta-cell sulfonylurea receptor (SUR1) missense variant (S1370A), but these linkage disequilibria did not differ between the NIDDM and control groups.
31	9032109	The results of these studies thus revealed that mutations in the coding region of Kir6.2 1) were not responsible for the previously noted association of the SUR1 variants with NIDDM (Inoue H et al., Diabetes 45:825-831, 1996) and 2) did not contribute to the impaired insulin secretion characteristic of NIDDM in Caucasian patients.
32	9032110	Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM.
33	9032110	The objective of this study was to search for mutations in the Kir6.2 gene that might be associated with NIDDM or related to altered insulin secretion, insulin action, or glucose metabolism in healthy subjects.
34	9032110	We conclude that a combination of common Kir6.2 amino acid variants may contribute to the genetic background behind the large variation of the insulin sensitivity index in the general population.
35	9032110	Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM.
36	9032110	The objective of this study was to search for mutations in the Kir6.2 gene that might be associated with NIDDM or related to altered insulin secretion, insulin action, or glucose metabolism in healthy subjects.
37	9032110	We conclude that a combination of common Kir6.2 amino acid variants may contribute to the genetic background behind the large variation of the insulin sensitivity index in the general population.
38	9032110	Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM.
39	9032110	The objective of this study was to search for mutations in the Kir6.2 gene that might be associated with NIDDM or related to altered insulin secretion, insulin action, or glucose metabolism in healthy subjects.
40	9032110	We conclude that a combination of common Kir6.2 amino acid variants may contribute to the genetic background behind the large variation of the insulin sensitivity index in the general population.
41	9100595	Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a rare disorder due to defective negative feedback regulation of insulin secretion by low glucose levels, is often familial.
42	9100595	Most cases are recessively inherited, and mutations of the sulfonylurea receptor gene (SUR) or the closely linked KIR6.2 gene have been found in several families.
43	9100595	By preliminary linkage analysis, we tested the possibility of a dominant negative SUR or KIR6.2 mutant.
44	9100595	The insulin (INS) and glucokinase (GCK) genes were also tested as additional candidates.
45	9100595	We conclude that mutation of a gene other than SUR or KIR6.2 is responsible for the dominant PHHI in this family, and this gene cannot be INS or GCK.
46	9100595	Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a rare disorder due to defective negative feedback regulation of insulin secretion by low glucose levels, is often familial.
47	9100595	Most cases are recessively inherited, and mutations of the sulfonylurea receptor gene (SUR) or the closely linked KIR6.2 gene have been found in several families.
48	9100595	By preliminary linkage analysis, we tested the possibility of a dominant negative SUR or KIR6.2 mutant.
49	9100595	The insulin (INS) and glucokinase (GCK) genes were also tested as additional candidates.
50	9100595	We conclude that mutation of a gene other than SUR or KIR6.2 is responsible for the dominant PHHI in this family, and this gene cannot be INS or GCK.
51	9100595	Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a rare disorder due to defective negative feedback regulation of insulin secretion by low glucose levels, is often familial.
52	9100595	Most cases are recessively inherited, and mutations of the sulfonylurea receptor gene (SUR) or the closely linked KIR6.2 gene have been found in several families.
53	9100595	By preliminary linkage analysis, we tested the possibility of a dominant negative SUR or KIR6.2 mutant.
54	9100595	The insulin (INS) and glucokinase (GCK) genes were also tested as additional candidates.
55	9100595	We conclude that mutation of a gene other than SUR or KIR6.2 is responsible for the dominant PHHI in this family, and this gene cannot be INS or GCK.
56	9100595	Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a rare disorder due to defective negative feedback regulation of insulin secretion by low glucose levels, is often familial.
57	9100595	Most cases are recessively inherited, and mutations of the sulfonylurea receptor gene (SUR) or the closely linked KIR6.2 gene have been found in several families.
58	9100595	By preliminary linkage analysis, we tested the possibility of a dominant negative SUR or KIR6.2 mutant.
59	9100595	The insulin (INS) and glucokinase (GCK) genes were also tested as additional candidates.
60	9100595	We conclude that mutation of a gene other than SUR or KIR6.2 is responsible for the dominant PHHI in this family, and this gene cannot be INS or GCK.
61	9200660	The 31-cM region of chromosome 11 including the obesity gene tubby and ATP-sensitive potassium channel genes, SUR1 and Kir6.2, does not contain a major susceptibility locus for NIDDM in 127 non-Hispanic white affected sibships.
62	9287044	Kir6.2, a member of the inward rectifier K+ channel family, is a component of the ATP-sensitive K+ (K[ATP]) channel considered to play a key role in glucose-induced insulin secretion.
63	9287044	In situ hybridization and immunofluorescence staining of serial sections with the anti-insulin, the anti-glucagon, and the anti-somatostatin antibodies showed Kir6.2 mRNA to be present in alpha-, beta-, and delta-cells.
64	9287044	Kir6.2 was further shown to be located together with insulin, glucagon, or somatostatin.
65	9287044	These results suggest that Kir6.2, as a component of K(ATP) channels, is an important molecule in the regulation of all the release of insulin, glucagon, and somatostatin.
66	9287044	Kir6.2, a member of the inward rectifier K+ channel family, is a component of the ATP-sensitive K+ (K[ATP]) channel considered to play a key role in glucose-induced insulin secretion.
67	9287044	In situ hybridization and immunofluorescence staining of serial sections with the anti-insulin, the anti-glucagon, and the anti-somatostatin antibodies showed Kir6.2 mRNA to be present in alpha-, beta-, and delta-cells.
68	9287044	Kir6.2 was further shown to be located together with insulin, glucagon, or somatostatin.
69	9287044	These results suggest that Kir6.2, as a component of K(ATP) channels, is an important molecule in the regulation of all the release of insulin, glucagon, and somatostatin.
70	9287044	Kir6.2, a member of the inward rectifier K+ channel family, is a component of the ATP-sensitive K+ (K[ATP]) channel considered to play a key role in glucose-induced insulin secretion.
71	9287044	In situ hybridization and immunofluorescence staining of serial sections with the anti-insulin, the anti-glucagon, and the anti-somatostatin antibodies showed Kir6.2 mRNA to be present in alpha-, beta-, and delta-cells.
72	9287044	Kir6.2 was further shown to be located together with insulin, glucagon, or somatostatin.
73	9287044	These results suggest that Kir6.2, as a component of K(ATP) channels, is an important molecule in the regulation of all the release of insulin, glucagon, and somatostatin.
74	9287044	Kir6.2, a member of the inward rectifier K+ channel family, is a component of the ATP-sensitive K+ (K[ATP]) channel considered to play a key role in glucose-induced insulin secretion.
75	9287044	In situ hybridization and immunofluorescence staining of serial sections with the anti-insulin, the anti-glucagon, and the anti-somatostatin antibodies showed Kir6.2 mRNA to be present in alpha-, beta-, and delta-cells.
76	9287044	Kir6.2 was further shown to be located together with insulin, glucagon, or somatostatin.
77	9287044	These results suggest that Kir6.2, as a component of K(ATP) channels, is an important molecule in the regulation of all the release of insulin, glucagon, and somatostatin.
78	9326676	The beta cell KATP channel is a complex of two proteins: Kir6.2 and SUR1.
79	9326676	The former is an ATP-sensitive K+-selective pore, whereas SUR1 is a channel regulator that endows Kir6.2 with sensitivity to sulfonylureas.
80	9326676	We have used a truncated form of Kir6.2, which expresses independently of SUR1, to show that phentolamine does not inhibit KATP channels by interacting with SUR1.
81	9326676	The beta cell KATP channel is a complex of two proteins: Kir6.2 and SUR1.
82	9326676	The former is an ATP-sensitive K+-selective pore, whereas SUR1 is a channel regulator that endows Kir6.2 with sensitivity to sulfonylureas.
83	9326676	We have used a truncated form of Kir6.2, which expresses independently of SUR1, to show that phentolamine does not inhibit KATP channels by interacting with SUR1.
84	9326676	The beta cell KATP channel is a complex of two proteins: Kir6.2 and SUR1.
85	9326676	The former is an ATP-sensitive K+-selective pore, whereas SUR1 is a channel regulator that endows Kir6.2 with sensitivity to sulfonylureas.
86	9326676	We have used a truncated form of Kir6.2, which expresses independently of SUR1, to show that phentolamine does not inhibit KATP channels by interacting with SUR1.
87	9356020	These channels comprise the sulfonylurea receptor (SUR1) and Kir6.2, a member of the inward rectifier K+ channel family.
88	9356020	A nonsense mutation, Tyr-->Stop at codon 12 (designated Y12X) was observed in the homozygous state in a single proband. 86Rb+ efflux measurements and single-channel recordings of COS-1 cells co-expressing SUR1 and either wild-type or Y12X mutant Kir6.2 proteins confirmed that K(ATP) channel activity was abolished by this nonsense mutation.
89	9356020	These channels comprise the sulfonylurea receptor (SUR1) and Kir6.2, a member of the inward rectifier K+ channel family.
90	9356020	A nonsense mutation, Tyr-->Stop at codon 12 (designated Y12X) was observed in the homozygous state in a single proband. 86Rb+ efflux measurements and single-channel recordings of COS-1 cells co-expressing SUR1 and either wild-type or Y12X mutant Kir6.2 proteins confirmed that K(ATP) channel activity was abolished by this nonsense mutation.
91	9458709	The molecular structure of KATP channels is thought to be a heteromultimeric (tetrameric) assembly of these complexes: Kir6.2 with SUR1 (SUR1/Kir6.2, pancreatic type), Kir6.2 with SUR2A (SUR2A/ Kir6.2, cardiac type), and Kir6.1 with SUR2B (SUR2B/Kir6.1, VSM type) [i.e., (SUR/Kir6.x)4].
92	9519757	To analyze possible functional alterations, we reconstituted the mutant K(ATP) by coexpressing beta-cell inward rectifier (BIR) (Kir 6.2), a channel subunit of K(ATP), and mutant SUR1 in HEK293T and COS-7 cells.
93	9618169	Mutations in both the Kir6.2 and sulfonylurea receptor (SUR1) genes have been associated with the autosomal recessive form of this disorder.
94	9648840	The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit, Kir6.2, regulates insulin secretion in the pancreas.
95	9648840	Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia.
96	9648840	We have studied the functional properties of novel SUR1 mutations identified in PHHI patients, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H.
97	9648840	R1394H and deltaF1388 SUR1, a previously identified PHHI mutation, resulted in no functional channels when coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q, and G1382S SUR1 generated functional channels in the absence of ATP.
98	9648840	The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit, Kir6.2, regulates insulin secretion in the pancreas.
99	9648840	Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia.
100	9648840	We have studied the functional properties of novel SUR1 mutations identified in PHHI patients, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H.
101	9648840	R1394H and deltaF1388 SUR1, a previously identified PHHI mutation, resulted in no functional channels when coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q, and G1382S SUR1 generated functional channels in the absence of ATP.
102	9648840	The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit, Kir6.2, regulates insulin secretion in the pancreas.
103	9648840	Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia.
104	9648840	We have studied the functional properties of novel SUR1 mutations identified in PHHI patients, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H.
105	9648840	R1394H and deltaF1388 SUR1, a previously identified PHHI mutation, resulted in no functional channels when coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q, and G1382S SUR1 generated functional channels in the absence of ATP.
106	9648840	The ATP-sensitive potassium channel, K(ATP) channel, a functional complex of the sulfonylurea receptor 1, SUR1, and an inward rectifier potassium channel subunit, Kir6.2, regulates insulin secretion in the pancreas.
107	9648840	Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia.
108	9648840	We have studied the functional properties of novel SUR1 mutations identified in PHHI patients, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H.
109	9648840	R1394H and deltaF1388 SUR1, a previously identified PHHI mutation, resulted in no functional channels when coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q, and G1382S SUR1 generated functional channels in the absence of ATP.
110	9703328	Cloning of the promoters for the beta-cell ATP-sensitive K-channel subunits Kir6.2 and SUR1.
111	9703328	The beta-cell ATP-sensitive potassium channel (K-ATP channel), which regulates insulin secretion, is composed of two types of subunits: 1) a sulfonylurea receptor (SUR1) and 2) an inwardly rectifying potassium channel (Kir6.2).
112	9703328	Several E-boxes and potential Sp1 sites are present in both promoters, and the Kir6.2 upstream region contains an Alu repeat.
113	9703328	Cloning of the promoters for the beta-cell ATP-sensitive K-channel subunits Kir6.2 and SUR1.
114	9703328	The beta-cell ATP-sensitive potassium channel (K-ATP channel), which regulates insulin secretion, is composed of two types of subunits: 1) a sulfonylurea receptor (SUR1) and 2) an inwardly rectifying potassium channel (Kir6.2).
115	9703328	Several E-boxes and potential Sp1 sites are present in both promoters, and the Kir6.2 upstream region contains an Alu repeat.
116	9703328	Cloning of the promoters for the beta-cell ATP-sensitive K-channel subunits Kir6.2 and SUR1.
117	9703328	The beta-cell ATP-sensitive potassium channel (K-ATP channel), which regulates insulin secretion, is composed of two types of subunits: 1) a sulfonylurea receptor (SUR1) and 2) an inwardly rectifying potassium channel (Kir6.2).
118	9703328	Several E-boxes and potential Sp1 sites are present in both promoters, and the Kir6.2 upstream region contains an Alu repeat.
119	9726229	The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively).
120	9726229	We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes.
121	9726229	Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity.
122	9726229	Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively).
123	9726229	Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible.
124	9726229	Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents.
125	9726229	The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively).
126	9726229	We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes.
127	9726229	Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity.
128	9726229	Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively).
129	9726229	Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible.
130	9726229	Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents.
131	9726229	The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively).
132	9726229	We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes.
133	9726229	Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity.
134	9726229	Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively).
135	9726229	Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible.
136	9726229	Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents.
137	9726229	The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively).
138	9726229	We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes.
139	9726229	Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity.
140	9726229	Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively).
141	9726229	Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible.
142	9726229	Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents.
143	9726229	The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively).
144	9726229	We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes.
145	9726229	Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity.
146	9726229	Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively).
147	9726229	Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible.
148	9726229	Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents.
149	9726229	The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively).
150	9726229	We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes.
151	9726229	Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity.
152	9726229	Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively).
153	9726229	Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible.
154	9726229	Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents.
155	9756869	Insulin secretion from pancreatic beta cells is coupled to cell metabolism through closure of ATP-sensitive potassium (KATP) channels, which comprise Kir6.2 and sulfonylurea receptor (SUR1) subunits.
156	9756869	We recorded macroscopic and single-channel currents from Xenopus oocytes expressing either Kir6.2/SUR1 or Kir6. 2DeltaC36 (which forms channels in the absence of SUR1).
157	9756869	Oleoyl-CoA (1 microM) activated both wild-type Kir6.2/SUR1 and Kir6.2DeltaC36 macroscopic currents, approximately 2-fold, by increasing the number and open probability of Kir6.2/SUR1 and Kir6.2DeltaC36 channels.
158	9756869	Oleoyl-CoA also impaired channel inhibition by ATP, increasing the Ki values for both Kir6.2/SUR1 and Kir6.2DeltaC36 currents by approximately 3-fold.
159	9756869	Insulin secretion from pancreatic beta cells is coupled to cell metabolism through closure of ATP-sensitive potassium (KATP) channels, which comprise Kir6.2 and sulfonylurea receptor (SUR1) subunits.
160	9756869	We recorded macroscopic and single-channel currents from Xenopus oocytes expressing either Kir6.2/SUR1 or Kir6. 2DeltaC36 (which forms channels in the absence of SUR1).
161	9756869	Oleoyl-CoA (1 microM) activated both wild-type Kir6.2/SUR1 and Kir6.2DeltaC36 macroscopic currents, approximately 2-fold, by increasing the number and open probability of Kir6.2/SUR1 and Kir6.2DeltaC36 channels.
162	9756869	Oleoyl-CoA also impaired channel inhibition by ATP, increasing the Ki values for both Kir6.2/SUR1 and Kir6.2DeltaC36 currents by approximately 3-fold.
163	9756869	Insulin secretion from pancreatic beta cells is coupled to cell metabolism through closure of ATP-sensitive potassium (KATP) channels, which comprise Kir6.2 and sulfonylurea receptor (SUR1) subunits.
164	9756869	We recorded macroscopic and single-channel currents from Xenopus oocytes expressing either Kir6.2/SUR1 or Kir6. 2DeltaC36 (which forms channels in the absence of SUR1).
165	9756869	Oleoyl-CoA (1 microM) activated both wild-type Kir6.2/SUR1 and Kir6.2DeltaC36 macroscopic currents, approximately 2-fold, by increasing the number and open probability of Kir6.2/SUR1 and Kir6.2DeltaC36 channels.
166	9756869	Oleoyl-CoA also impaired channel inhibition by ATP, increasing the Ki values for both Kir6.2/SUR1 and Kir6.2DeltaC36 currents by approximately 3-fold.
167	9756869	Insulin secretion from pancreatic beta cells is coupled to cell metabolism through closure of ATP-sensitive potassium (KATP) channels, which comprise Kir6.2 and sulfonylurea receptor (SUR1) subunits.
168	9756869	We recorded macroscopic and single-channel currents from Xenopus oocytes expressing either Kir6.2/SUR1 or Kir6. 2DeltaC36 (which forms channels in the absence of SUR1).
169	9756869	Oleoyl-CoA (1 microM) activated both wild-type Kir6.2/SUR1 and Kir6.2DeltaC36 macroscopic currents, approximately 2-fold, by increasing the number and open probability of Kir6.2/SUR1 and Kir6.2DeltaC36 channels.
170	9756869	Oleoyl-CoA also impaired channel inhibition by ATP, increasing the Ki values for both Kir6.2/SUR1 and Kir6.2DeltaC36 currents by approximately 3-fold.
171	9813050	The ATP-dependent potassium (KATP) channel in the pancreatic beta-cell is a complex of two proteins, the pore-forming Kir6.2 and the sulfonylurea receptor type 1 (SUR1).
172	9885743	Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes.
173	9885743	Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.
174	9885743	Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes.
175	9885743	Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.
176	10199129	A lot of key molecules of the systems, including GLUT2, glucokinase, SUR1, Kir6.2 and CD38, have been cloned and characterized whether the mutations in these genes are responsible for the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM).
177	10204114	The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry.
178	10204114	The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4.
179	10204114	The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane.
180	10204114	The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity.
181	10204114	PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides.
182	10204114	An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1.
183	10204114	A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP.
184	10204114	The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry.
185	10204114	The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4.
186	10204114	The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane.
187	10204114	The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity.
188	10204114	PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides.
189	10204114	An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1.
190	10204114	A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP.
191	10204114	The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry.
192	10204114	The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4.
193	10204114	The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane.
194	10204114	The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity.
195	10204114	PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides.
196	10204114	An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1.
197	10204114	A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP.
198	10204114	The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry.
199	10204114	The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4.
200	10204114	The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane.
201	10204114	The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity.
202	10204114	PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides.
203	10204114	An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1.
204	10204114	A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP.
205	10204114	The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry.
206	10204114	The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4.
207	10204114	The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane.
208	10204114	The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity.
209	10204114	PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides.
210	10204114	An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1.
211	10204114	A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP.
212	10204114	The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry.
213	10204114	The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4.
214	10204114	The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane.
215	10204114	The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity.
216	10204114	PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides.
217	10204114	An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1.
218	10204114	A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP.
219	10204114	The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry.
220	10204114	The pore of the channel is formed by KIR6.2 in a tetrameric arrangement; the overall stoichiometry of active channels is (SUR1/KIR6.2)4.
221	10204114	The single-channel conductance of the homomeric KIR6.2 channels is equivalent to SUR/KIR6.2 channels, but they differ in all other respects, including bursting behavior, pharmacological properties, sensitivity to ATP and ADP, and trafficking to the plasma membrane.
222	10204114	The key role KATP channel play in the regulation of insulin secretion in response to changes in glucose metabolism is underscored by the finding that a recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is caused by mutations in KATP channel subunits that result in the loss of channel activity.
223	10204114	PHHI mutations have been informative on the function of SUR1 and regulation of KATP channels by adenine nucleotides.
224	10204114	An unexpected finding is that the inhibitory action of ATP appears to be through a site located on KIR6.2, whose affinity for ATP is modified by SUR1.
225	10204114	A PHHI mutation, G1479R, in the second NBF of SUR1 forms active KATP channels that respond normally to ATP, but fail to activate with MgADP.
226	10334322	Mutations in genes encoding the ATP-regulated potassium (K(ATP)) channels of the pancreatic beta-cell (SUR1 and Kir6.2) are the major known cause of persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
227	10334322	Haplotype analysis using polymorphic markers spanning the SUR1/Kir6.2 gene cluster confirmed linkage to the 11p region.
228	10334322	No K(ATP) channel activity was observed in beta-cells isolated from a homozygous patient or after coexpression of recombinant Kir6.2 and SUR1 carrying the V187D mutation.
229	10334322	This unique SUR1 mutation explains the majority of PHHI cases in Finland and is strongly associated with a severe form of the disease.
230	10334322	Mutations in genes encoding the ATP-regulated potassium (K(ATP)) channels of the pancreatic beta-cell (SUR1 and Kir6.2) are the major known cause of persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
231	10334322	Haplotype analysis using polymorphic markers spanning the SUR1/Kir6.2 gene cluster confirmed linkage to the 11p region.
232	10334322	No K(ATP) channel activity was observed in beta-cells isolated from a homozygous patient or after coexpression of recombinant Kir6.2 and SUR1 carrying the V187D mutation.
233	10334322	This unique SUR1 mutation explains the majority of PHHI cases in Finland and is strongly associated with a severe form of the disease.
234	10334322	Mutations in genes encoding the ATP-regulated potassium (K(ATP)) channels of the pancreatic beta-cell (SUR1 and Kir6.2) are the major known cause of persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
235	10334322	Haplotype analysis using polymorphic markers spanning the SUR1/Kir6.2 gene cluster confirmed linkage to the 11p region.
236	10334322	No K(ATP) channel activity was observed in beta-cells isolated from a homozygous patient or after coexpression of recombinant Kir6.2 and SUR1 carrying the V187D mutation.
237	10334322	This unique SUR1 mutation explains the majority of PHHI cases in Finland and is strongly associated with a severe form of the disease.
238	10334322	Mutations in genes encoding the ATP-regulated potassium (K(ATP)) channels of the pancreatic beta-cell (SUR1 and Kir6.2) are the major known cause of persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
239	10334322	Haplotype analysis using polymorphic markers spanning the SUR1/Kir6.2 gene cluster confirmed linkage to the 11p region.
240	10334322	No K(ATP) channel activity was observed in beta-cells isolated from a homozygous patient or after coexpression of recombinant Kir6.2 and SUR1 carrying the V187D mutation.
241	10334322	This unique SUR1 mutation explains the majority of PHHI cases in Finland and is strongly associated with a severe form of the disease.
242	10338089	K(ATP) channel is a complex composed of at least two subunits: the sulfonylurea receptor SUR1 and Kir6.2, an inward rectifier K+ channel member.
243	10338089	Mutations in both subunits have been identified in patients with the autosomal recessive form of hyperinsulinism, including 28 different mutations in the SUR1 gene and two mutations in the Kir6.2 gene.
244	10338089	Inadequately high insulin secretion in one family with an autosomal dominant mode of inheritance is caused by a mutation in the glucokinase gene, resulting in increased affinity of the enzyme for glucose.
245	10338089	The new molecular approaches in PHHI give further insight into the mechanism of pancreatic beta cell insulin secretion.
246	10338089	K(ATP) channel is a complex composed of at least two subunits: the sulfonylurea receptor SUR1 and Kir6.2, an inward rectifier K+ channel member.
247	10338089	Mutations in both subunits have been identified in patients with the autosomal recessive form of hyperinsulinism, including 28 different mutations in the SUR1 gene and two mutations in the Kir6.2 gene.
248	10338089	Inadequately high insulin secretion in one family with an autosomal dominant mode of inheritance is caused by a mutation in the glucokinase gene, resulting in increased affinity of the enzyme for glucose.
249	10338089	The new molecular approaches in PHHI give further insight into the mechanism of pancreatic beta cell insulin secretion.
250	10338089	K(ATP) channel is a complex composed of at least two subunits: the sulfonylurea receptor SUR1 and Kir6.2, an inward rectifier K+ channel member.
251	10338089	Mutations in both subunits have been identified in patients with the autosomal recessive form of hyperinsulinism, including 28 different mutations in the SUR1 gene and two mutations in the Kir6.2 gene.
252	10338089	Inadequately high insulin secretion in one family with an autosomal dominant mode of inheritance is caused by a mutation in the glucokinase gene, resulting in increased affinity of the enzyme for glucose.
253	10338089	The new molecular approaches in PHHI give further insight into the mechanism of pancreatic beta cell insulin secretion.
254	10342826	ATP-sensitive potassium channels (K(ATP)) are formed from four pore-forming Kir6.2 subunits complexed with four regulatory sulfonylurea receptor subunits (SUR1 in pancreatic beta-cells, SUR2A in heart).
255	10342826	Chimeric SURs were coexpressed with Kir6.2 in Xenopus oocytes, and macroscopic currents were measured in inside-out membrane patches.
256	10342826	ATP-sensitive potassium channels (K(ATP)) are formed from four pore-forming Kir6.2 subunits complexed with four regulatory sulfonylurea receptor subunits (SUR1 in pancreatic beta-cells, SUR2A in heart).
257	10342826	Chimeric SURs were coexpressed with Kir6.2 in Xenopus oocytes, and macroscopic currents were measured in inside-out membrane patches.
258	10373428	The proximal promoter region contains multiple SP1-binding sites, and cotransfection experiments of the SUR1 promoter-luciferase vector with SP1 expression vector in Drosophila SL2 cells demonstrated a stimulatory effect of SP1 on SUR1 transcriptional activity.
259	10373428	The mobility shift assays confirmed the interaction of the SP1 transcription factor with the proximal promoter region of the SUR1 gene.
260	10373428	Together, these results indicate that SP1 may mediate transcription initiation of the SUR1 gene.
261	10373428	SUR1 and Kir6.2 mRNA levels are down-regulated by approximately 40-50% in response to glucocorticoid treatment.
262	10373428	Studies of mRNA turnover demonstrate that glucocorticoids most likely decrease the transcriptional activity of both SUR1 and Kir6.2 genes since glucocorticoids failed to affect the stability of each mRNA.
263	10373428	Likewise, the reduction in mRNA levels was correlated with a decrease in SUR1 and Kir6.2 protein levels.
264	10373428	The proximal promoter region contains multiple SP1-binding sites, and cotransfection experiments of the SUR1 promoter-luciferase vector with SP1 expression vector in Drosophila SL2 cells demonstrated a stimulatory effect of SP1 on SUR1 transcriptional activity.
265	10373428	The mobility shift assays confirmed the interaction of the SP1 transcription factor with the proximal promoter region of the SUR1 gene.
266	10373428	Together, these results indicate that SP1 may mediate transcription initiation of the SUR1 gene.
267	10373428	SUR1 and Kir6.2 mRNA levels are down-regulated by approximately 40-50% in response to glucocorticoid treatment.
268	10373428	Studies of mRNA turnover demonstrate that glucocorticoids most likely decrease the transcriptional activity of both SUR1 and Kir6.2 genes since glucocorticoids failed to affect the stability of each mRNA.
269	10373428	Likewise, the reduction in mRNA levels was correlated with a decrease in SUR1 and Kir6.2 protein levels.
270	10373428	The proximal promoter region contains multiple SP1-binding sites, and cotransfection experiments of the SUR1 promoter-luciferase vector with SP1 expression vector in Drosophila SL2 cells demonstrated a stimulatory effect of SP1 on SUR1 transcriptional activity.
271	10373428	The mobility shift assays confirmed the interaction of the SP1 transcription factor with the proximal promoter region of the SUR1 gene.
272	10373428	Together, these results indicate that SP1 may mediate transcription initiation of the SUR1 gene.
273	10373428	SUR1 and Kir6.2 mRNA levels are down-regulated by approximately 40-50% in response to glucocorticoid treatment.
274	10373428	Studies of mRNA turnover demonstrate that glucocorticoids most likely decrease the transcriptional activity of both SUR1 and Kir6.2 genes since glucocorticoids failed to affect the stability of each mRNA.
275	10373428	Likewise, the reduction in mRNA levels was correlated with a decrease in SUR1 and Kir6.2 protein levels.
276	10512365	The ATP-sensitive K+ (K(ATP)) channels in MIN6 cells comprise inwardly rectifying K+ channel member Kir6.2 subunits and sulfonylurea receptor (SUR) 1 subunits.
277	10512365	Both SUR1 and Kir6.2 mRNA levels were not altered, but SUR1 protein was rather increased in MIN6-Glib.
278	10512365	The ATP-sensitive K+ (K(ATP)) channels in MIN6 cells comprise inwardly rectifying K+ channel member Kir6.2 subunits and sulfonylurea receptor (SUR) 1 subunits.
279	10512365	Both SUR1 and Kir6.2 mRNA levels were not altered, but SUR1 protein was rather increased in MIN6-Glib.
280	10567373	Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a neonatal disease characterized by dysregulation of insulin secretion accompanied by profound hypoglycemia.
281	10567373	The PHHI-derived cell line (NES2Y) exhibits insulin secretory characteristics typical of islet cells derived from these patients, i.e. they have no K(ATP) channel activity and as a consequence secrete insulin at constitutively high levels in the absence of glucose.
282	10567373	In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression.
283	10567373	To repair these defects NES2Y cells were triple-transfected with cDNAs encoding the two components of the K(ATP) channel (SUR1 and Kir6.2) and PDX1.
284	10567373	This approach to engineering PHHI-derived islet cells may be of use in gene therapy for PHHI and in cell engineering techniques for administering insulin for the treatment of diabetes mellitus.
285	10567373	Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a neonatal disease characterized by dysregulation of insulin secretion accompanied by profound hypoglycemia.
286	10567373	The PHHI-derived cell line (NES2Y) exhibits insulin secretory characteristics typical of islet cells derived from these patients, i.e. they have no K(ATP) channel activity and as a consequence secrete insulin at constitutively high levels in the absence of glucose.
287	10567373	In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression.
288	10567373	To repair these defects NES2Y cells were triple-transfected with cDNAs encoding the two components of the K(ATP) channel (SUR1 and Kir6.2) and PDX1.
289	10567373	This approach to engineering PHHI-derived islet cells may be of use in gene therapy for PHHI and in cell engineering techniques for administering insulin for the treatment of diabetes mellitus.
290	10567373	Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a neonatal disease characterized by dysregulation of insulin secretion accompanied by profound hypoglycemia.
291	10567373	The PHHI-derived cell line (NES2Y) exhibits insulin secretory characteristics typical of islet cells derived from these patients, i.e. they have no K(ATP) channel activity and as a consequence secrete insulin at constitutively high levels in the absence of glucose.
292	10567373	In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression.
293	10567373	To repair these defects NES2Y cells were triple-transfected with cDNAs encoding the two components of the K(ATP) channel (SUR1 and Kir6.2) and PDX1.
294	10567373	This approach to engineering PHHI-derived islet cells may be of use in gene therapy for PHHI and in cell engineering techniques for administering insulin for the treatment of diabetes mellitus.
295	10567373	Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a neonatal disease characterized by dysregulation of insulin secretion accompanied by profound hypoglycemia.
296	10567373	The PHHI-derived cell line (NES2Y) exhibits insulin secretory characteristics typical of islet cells derived from these patients, i.e. they have no K(ATP) channel activity and as a consequence secrete insulin at constitutively high levels in the absence of glucose.
297	10567373	In addition, they exhibit impaired expression of the homeodomain transcription factor PDX1, which is a key component of the signaling pathway linking nutrient metabolism to the regulation of insulin gene expression.
298	10567373	To repair these defects NES2Y cells were triple-transfected with cDNAs encoding the two components of the K(ATP) channel (SUR1 and Kir6.2) and PDX1.
299	10567373	This approach to engineering PHHI-derived islet cells may be of use in gene therapy for PHHI and in cell engineering techniques for administering insulin for the treatment of diabetes mellitus.
300	10615958	To elucidate the genetic etiology of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in the Japanese population, we conducted a polymerase chain reaction-single-strand conformation polymorphism analysis of the sulfonylurea receptor 1 (SUR1) and Kir6.2 genes in 17 Japanese PHHI patients, including a pair of siblings from a consanguineous family.
301	10615958	The inhibition is probably mediated through direct ATP interaction with a pore-forming subunit Kir6.2, whereas the activation is likely to be through a regulatory subunit SUR1.
302	10615958	To elucidate the genetic etiology of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in the Japanese population, we conducted a polymerase chain reaction-single-strand conformation polymorphism analysis of the sulfonylurea receptor 1 (SUR1) and Kir6.2 genes in 17 Japanese PHHI patients, including a pair of siblings from a consanguineous family.
303	10615958	The inhibition is probably mediated through direct ATP interaction with a pore-forming subunit Kir6.2, whereas the activation is likely to be through a regulatory subunit SUR1.
304	10866047	Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y.
305	10866047	NES2Y cells, like beta-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (KATP) and also carry a defect in the insulin gene-regulatory transcription factor PDX1.
306	10866047	Here, we report that the NES2Y beta-cells that are transfected with the genes encoding the components of KATP channels in beta-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational KATP channels and show normal intracellular Ca2+ and secretory responses to glucose.
307	10866047	NES2Y beta-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional KATP channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent beta-cell agonists.
308	10866047	Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y.
309	10866047	NES2Y cells, like beta-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (KATP) and also carry a defect in the insulin gene-regulatory transcription factor PDX1.
310	10866047	Here, we report that the NES2Y beta-cells that are transfected with the genes encoding the components of KATP channels in beta-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational KATP channels and show normal intracellular Ca2+ and secretory responses to glucose.
311	10866047	NES2Y beta-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional KATP channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent beta-cell agonists.
312	10866047	Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y.
313	10866047	NES2Y cells, like beta-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (KATP) and also carry a defect in the insulin gene-regulatory transcription factor PDX1.
314	10866047	Here, we report that the NES2Y beta-cells that are transfected with the genes encoding the components of KATP channels in beta-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational KATP channels and show normal intracellular Ca2+ and secretory responses to glucose.
315	10866047	NES2Y beta-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional KATP channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent beta-cell agonists.
316	10868950	Interestingly, despite the severe defect in glucose-induced insulin secretion, Kir6.2 knockout mice show only a very mild impairment in glucose tolerance.
317	10868950	However, when the knockout mice become obese with age, they develop fasting hyperglycemia and glucose intolerance, while neither fasting hyperglycemia nor glucose intolerance is evident in the aged knockout mice without obesity, suggesting that both the genetic defect in glucose-induced insulin secretion and the acquired insulin resistance due to environmental factors are necessary to develop diabetes in Kir6.2 knockout mice.
318	10868950	Interestingly, despite the severe defect in glucose-induced insulin secretion, Kir6.2 knockout mice show only a very mild impairment in glucose tolerance.
319	10868950	However, when the knockout mice become obese with age, they develop fasting hyperglycemia and glucose intolerance, while neither fasting hyperglycemia nor glucose intolerance is evident in the aged knockout mice without obesity, suggesting that both the genetic defect in glucose-induced insulin secretion and the acquired insulin resistance due to environmental factors are necessary to develop diabetes in Kir6.2 knockout mice.
320	10905475	In pancreatic beta-cells, glucokinase (GK), the rate-limiting enzyme in glycolysis, mediates glucose-induced insulin release by regulating intracellular ATP production.
321	10905475	In the arcuate nucleus, >75% of neuropeptide Y-positive neurons also expressed GK, and most GK+ neurons also expressed KIR6.2 (the pore-forming subunit of the ATP-sensitive K+ channel).
322	10905475	The specific anatomic localization of GK mRNA in hypothalamic areas known to contain glucosensing neurons and the coexpression of KIR6.2 and NPY in GK+ neurons support a role for GK as a primary determinant of glucosensing in neuropeptide neurons that integrate multiple signals relating to peripheral energy metabolism.
323	10905475	In pancreatic beta-cells, glucokinase (GK), the rate-limiting enzyme in glycolysis, mediates glucose-induced insulin release by regulating intracellular ATP production.
324	10905475	In the arcuate nucleus, >75% of neuropeptide Y-positive neurons also expressed GK, and most GK+ neurons also expressed KIR6.2 (the pore-forming subunit of the ATP-sensitive K+ channel).
325	10905475	The specific anatomic localization of GK mRNA in hypothalamic areas known to contain glucosensing neurons and the coexpression of KIR6.2 and NPY in GK+ neurons support a role for GK as a primary determinant of glucosensing in neuropeptide neurons that integrate multiple signals relating to peripheral energy metabolism.
326	10969823	These channels are heteromultimers composed with a 4:4 stoichiometry of an inwardly rectifying K+ channel subunit (Kir6.2) plus a regulatory sulfonylurea receptor.
327	10969823	This architecture might facilitate coupling of [ATP(4-)] to insulin secretion and may protect against diabetic dysregulation resulting from heterozygous mutations in Kir6.2.
328	10969823	These channels are heteromultimers composed with a 4:4 stoichiometry of an inwardly rectifying K+ channel subunit (Kir6.2) plus a regulatory sulfonylurea receptor.
329	10969823	This architecture might facilitate coupling of [ATP(4-)] to insulin secretion and may protect against diabetic dysregulation resulting from heterozygous mutations in Kir6.2.
330	11018078	These channels consist of two types of protein subunit: the sulfonylurea receptor SUR1 and the inward rectifying potassium channel Kir6.2.
331	11018078	This clinical finding is in agreement with the results of heterologous coexpression studies of recombinant Kir6.2 and SUR1 carrying the E1506K mutation.
332	11018078	These channels consist of two types of protein subunit: the sulfonylurea receptor SUR1 and the inward rectifying potassium channel Kir6.2.
333	11018078	This clinical finding is in agreement with the results of heterologous coexpression studies of recombinant Kir6.2 and SUR1 carrying the E1506K mutation.
334	11078449	The factors that influence functional coupling between the sulfonylurea receptor (SUR1) and Kir6.2 subunits of ATP-sensitive K+ (K+(ATP)) channels were studied in rat pancreatic beta-cells using patch clamp and microfluorometric techniques.
335	11078449	The modification, which may reflect functional disconnection between SUR1 and Kir6.2, is prevented by ATP and PIP2, which may act cooperatively to stabilize membrane cytoskeletons (F-actin structures).
336	11078449	The factors that influence functional coupling between the sulfonylurea receptor (SUR1) and Kir6.2 subunits of ATP-sensitive K+ (K+(ATP)) channels were studied in rat pancreatic beta-cells using patch clamp and microfluorometric techniques.
337	11078449	The modification, which may reflect functional disconnection between SUR1 and Kir6.2, is prevented by ATP and PIP2, which may act cooperatively to stabilize membrane cytoskeletons (F-actin structures).
338	11078468	Glibenclamide and glimepiride, on the other hand, block channels containing SUR1 and SUR2 with similar affinity.
339	11078468	Tolbutamide and gliclazide produce a reversible inhibition of Kir6.2/SUR1 and Kir6.2/SUR2 channels, whereas glibenclamide has a reversible effect on cardiac, but not beta-cell, K(ATP) channels.
340	11252820	Interleukin 1 (IL-1) is a pleiotropic cytokine with the potential to kill pancreatic beta-cells, and this unique property is thought to be involved in the pathogenesis of type I diabetes mellitus.
341	11252820	Many of the differentially regulated genes are known to play a role in immune- and stress-related pathways as well as in insulin secretion and vesicle trafficking, e.g. alpha-endosulfine and K+ channel Kir6.2 are differentially regulated.
342	11272201	Interestingly, the number of peptide YY (PYY) and glucagon-positive cells is markedly increased in Kir6.2 null mice, whereas the number of PP cells and delta-cells is not altered.
343	11318841	Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53).
344	11472276	Electrophysiological and biochemical evidence suggest that the I3 site may be intrinsic to the ion-conducting pore component, Kir6.2, of the K(ATP) channel, but the effects of imidazoline ligands on insulin secretion can be dissociated from the regulation of Kir6.2.
345	11574406	K(ATP) channels in muscle and beta-cells share a common pore-forming subunit, Kir6.2, but possess alternative sulfonylurea receptors (SURs; SUR1 in beta-cells, SUR2A in cardiac muscle, and SUR2B in smooth muscle).
346	11574406	Nicorandil activated Kir6.2/SUR2A and Kir6.2/SUR2B but not Kir6.2/SUR1 currents, consistent with its specificity for cardiac and smooth muscle K(ATP) channels.
347	11574406	K(ATP) channels in muscle and beta-cells share a common pore-forming subunit, Kir6.2, but possess alternative sulfonylurea receptors (SURs; SUR1 in beta-cells, SUR2A in cardiac muscle, and SUR2B in smooth muscle).
348	11574406	Nicorandil activated Kir6.2/SUR2A and Kir6.2/SUR2B but not Kir6.2/SUR1 currents, consistent with its specificity for cardiac and smooth muscle K(ATP) channels.
349	11723059	Most cases of hyperinsulinism of infancy (HI) are caused by mutations in either the sulfonylurea receptor-1 (SUR1) or the inward rectifying K(+) channel Kir6.2, two subunits of the beta-cell ATP-sensitive K(+) channel (K(ATP) channel).
350	11723059	Focal HI consists of adenomatous hyperplasia within a limited region of the pancreas, and it is caused by somatic loss of heterozygosity (LOH), including maternal Ch11p15-ter in a beta-cell precursor carrying a germ-line mutation in the paternal allele of SUR1 or Kir6.2.
351	11723059	Several imprinted genes are located within this chromosomal region, some of which, including p57(KIP2) and IGF-II, have been associated with the regulation of cell proliferation.
352	11723059	The fraction of beta-cells expressing p57(KIP2) did not vary significantly during development. beta-Cells within the focal lesions did not express p57(KIP2), whereas IGF-II staining inside focal lesions was mildly increased compared with unaffected surrounding tissue.
353	11723059	Most cases of hyperinsulinism of infancy (HI) are caused by mutations in either the sulfonylurea receptor-1 (SUR1) or the inward rectifying K(+) channel Kir6.2, two subunits of the beta-cell ATP-sensitive K(+) channel (K(ATP) channel).
354	11723059	Focal HI consists of adenomatous hyperplasia within a limited region of the pancreas, and it is caused by somatic loss of heterozygosity (LOH), including maternal Ch11p15-ter in a beta-cell precursor carrying a germ-line mutation in the paternal allele of SUR1 or Kir6.2.
355	11723059	Several imprinted genes are located within this chromosomal region, some of which, including p57(KIP2) and IGF-II, have been associated with the regulation of cell proliferation.
356	11723059	The fraction of beta-cells expressing p57(KIP2) did not vary significantly during development. beta-Cells within the focal lesions did not express p57(KIP2), whereas IGF-II staining inside focal lesions was mildly increased compared with unaffected surrounding tissue.
357	11780755	This signalling mechanism depends on glucose metabolism and requires the presence of specific molecules such as GLUT2, glucokinase and the K(ATP) channel subunits Kir6.2 and SUR1.
358	11938023	The pancreatic B-cell ATP-sensitive potassium channel (K(ATP)) is composed of two distinct subunits, an inwardly rectifying ion channel forming the pore (Kir6.2), and a regulatory subunit, namely the sulfonylurea receptor-1 (SUR1), which binds this widely used class of insulin-secreting drugs.
359	11938023	Mutations in the genes encoding Kir6.2 and SUR1 may result in familial persistent hyperinsulinemic hypoglycaemia of infancy, demonstrating their role in the regulation of insulin secretion.
360	11938023	Studies in various populations with different ethnic background provided evidence that various alleles of single nucleotide polymorphisms (SNPs) in the SUR1 gene, and to a less extent in the Kir6.2 gene, confer a significantly increased risk for the development of type 2 diabetes mellitus (T2DM).
361	11938023	The pancreatic B-cell ATP-sensitive potassium channel (K(ATP)) is composed of two distinct subunits, an inwardly rectifying ion channel forming the pore (Kir6.2), and a regulatory subunit, namely the sulfonylurea receptor-1 (SUR1), which binds this widely used class of insulin-secreting drugs.
362	11938023	Mutations in the genes encoding Kir6.2 and SUR1 may result in familial persistent hyperinsulinemic hypoglycaemia of infancy, demonstrating their role in the regulation of insulin secretion.
363	11938023	Studies in various populations with different ethnic background provided evidence that various alleles of single nucleotide polymorphisms (SNPs) in the SUR1 gene, and to a less extent in the Kir6.2 gene, confer a significantly increased risk for the development of type 2 diabetes mellitus (T2DM).
364	11938023	The pancreatic B-cell ATP-sensitive potassium channel (K(ATP)) is composed of two distinct subunits, an inwardly rectifying ion channel forming the pore (Kir6.2), and a regulatory subunit, namely the sulfonylurea receptor-1 (SUR1), which binds this widely used class of insulin-secreting drugs.
365	11938023	Mutations in the genes encoding Kir6.2 and SUR1 may result in familial persistent hyperinsulinemic hypoglycaemia of infancy, demonstrating their role in the regulation of insulin secretion.
366	11938023	Studies in various populations with different ethnic background provided evidence that various alleles of single nucleotide polymorphisms (SNPs) in the SUR1 gene, and to a less extent in the Kir6.2 gene, confer a significantly increased risk for the development of type 2 diabetes mellitus (T2DM).
367	12031979	The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener.
368	12031979	Here, we report functional studies of the Kir6.2/SUR1 Selective PCO 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide (NNC 55-9216).
369	12031979	We recorded cloned K(ATP) channel currents from inside-out patches excised from Xenopus laevis oocytes heterologously expressing Kir6.2/SUR1, Kir6.2/SUR2A, or Kir6.2/SUR2B, corresponding to the beta-cell, cardiac, and smooth muscle types of the K(ATP) channel.
370	12031979	NNC 55-9216 reversibly activated Kir6.2/SUR1 currents (EC(50) = 16 micromol/l).
371	12031979	The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener.
372	12031979	Here, we report functional studies of the Kir6.2/SUR1 Selective PCO 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide (NNC 55-9216).
373	12031979	We recorded cloned K(ATP) channel currents from inside-out patches excised from Xenopus laevis oocytes heterologously expressing Kir6.2/SUR1, Kir6.2/SUR2A, or Kir6.2/SUR2B, corresponding to the beta-cell, cardiac, and smooth muscle types of the K(ATP) channel.
374	12031979	NNC 55-9216 reversibly activated Kir6.2/SUR1 currents (EC(50) = 16 micromol/l).
375	12031979	The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener.
376	12031979	Here, we report functional studies of the Kir6.2/SUR1 Selective PCO 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide (NNC 55-9216).
377	12031979	We recorded cloned K(ATP) channel currents from inside-out patches excised from Xenopus laevis oocytes heterologously expressing Kir6.2/SUR1, Kir6.2/SUR2A, or Kir6.2/SUR2B, corresponding to the beta-cell, cardiac, and smooth muscle types of the K(ATP) channel.
378	12031979	NNC 55-9216 reversibly activated Kir6.2/SUR1 currents (EC(50) = 16 micromol/l).
379	12031979	The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener.
380	12031979	Here, we report functional studies of the Kir6.2/SUR1 Selective PCO 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide (NNC 55-9216).
381	12031979	We recorded cloned K(ATP) channel currents from inside-out patches excised from Xenopus laevis oocytes heterologously expressing Kir6.2/SUR1, Kir6.2/SUR2A, or Kir6.2/SUR2B, corresponding to the beta-cell, cardiac, and smooth muscle types of the K(ATP) channel.
382	12031979	NNC 55-9216 reversibly activated Kir6.2/SUR1 currents (EC(50) = 16 micromol/l).
383	12196469	RT-PCR detected the K(ATP) channel subunits Kir6.2 and SUR1 and glucokinase.
384	12196472	The inhibitory effect of these drugs was investigated on recombinant wild-type and mutant Kir6.2/SUR1 channels expressed in HEK293 cells.
385	12196472	Nateglinide and repaglinide dose-dependently inhibited whole-cell Kir6.2/SUR1 currents with half-maximal inhibitory concentration (IC(50)) values of 800 and 21 nmol/l, respectively.
386	12196472	Radioligand binding studies revealed a single high-affinity binding site for [(3)H]repaglinide on membranes prepared from HEK293 cells expressing wild-type (equilibrium dissociation constant [K(D)] = 0.40 nmol/l) or mutant (K(D) = 0.31 nmol/l) Kir6.2/SUR1 channels.
387	12196472	The inhibitory effect of these drugs was investigated on recombinant wild-type and mutant Kir6.2/SUR1 channels expressed in HEK293 cells.
388	12196472	Nateglinide and repaglinide dose-dependently inhibited whole-cell Kir6.2/SUR1 currents with half-maximal inhibitory concentration (IC(50)) values of 800 and 21 nmol/l, respectively.
389	12196472	Radioligand binding studies revealed a single high-affinity binding site for [(3)H]repaglinide on membranes prepared from HEK293 cells expressing wild-type (equilibrium dissociation constant [K(D)] = 0.40 nmol/l) or mutant (K(D) = 0.31 nmol/l) Kir6.2/SUR1 channels.
390	12196472	The inhibitory effect of these drugs was investigated on recombinant wild-type and mutant Kir6.2/SUR1 channels expressed in HEK293 cells.
391	12196472	Nateglinide and repaglinide dose-dependently inhibited whole-cell Kir6.2/SUR1 currents with half-maximal inhibitory concentration (IC(50)) values of 800 and 21 nmol/l, respectively.
392	12196472	Radioligand binding studies revealed a single high-affinity binding site for [(3)H]repaglinide on membranes prepared from HEK293 cells expressing wild-type (equilibrium dissociation constant [K(D)] = 0.40 nmol/l) or mutant (K(D) = 0.31 nmol/l) Kir6.2/SUR1 channels.
393	12196481	In conclusion, our findings suggest that the common Glu23Lys polymorphism in KIR6.2 is not necessarily associated with beta-cell dysfunction or insulin resistance but with diminished suppression of glucagon secretion in response to hyperglycemia.
394	12351459	Variations in insulin secretion in carriers of the E23K variant in the KIR6.2 subunit of the ATP-sensitive K(+) channel in the beta-cell.
395	12351459	We have examined glucose-stimulated insulin secretion in relation to this KIR6.2 gene variant in two independent Dutch cohorts.
396	12351459	We conclude that the E23K mutation in the KIR6.2 gene is not associated with detectable alterations in glucose-stimulated insulin secretion in two independent populations from the Netherlands.
397	12351459	Variations in insulin secretion in carriers of the E23K variant in the KIR6.2 subunit of the ATP-sensitive K(+) channel in the beta-cell.
398	12351459	We have examined glucose-stimulated insulin secretion in relation to this KIR6.2 gene variant in two independent Dutch cohorts.
399	12351459	We conclude that the E23K mutation in the KIR6.2 gene is not associated with detectable alterations in glucose-stimulated insulin secretion in two independent populations from the Netherlands.
400	12351459	Variations in insulin secretion in carriers of the E23K variant in the KIR6.2 subunit of the ATP-sensitive K(+) channel in the beta-cell.
401	12351459	We have examined glucose-stimulated insulin secretion in relation to this KIR6.2 gene variant in two independent Dutch cohorts.
402	12351459	We conclude that the E23K mutation in the KIR6.2 gene is not associated with detectable alterations in glucose-stimulated insulin secretion in two independent populations from the Netherlands.
403	12400064	The four known genetic causes for inborn hyperinsulinism (mutations in the genes ABCC8, KCNJ11, GLUD1, and GCK) were excluded.
404	12438314	At the same time points, high hyperglycemia rats showed a global alteration in gene expression with decreased mRNA for insulin, IAPP, islet-associated transcription factors (pancreatic and duodenal homeobox-1, BETA2/NeuroD, Nkx6.1, and hepatocyte nuclear factor 1 alpha), beta-cell metabolic enzymes (glucose transporter 2, glucokinase, mitochondrial glycerol phosphate dehydrogenase, and pyruvate carboxylase), and ion channels/pumps (Kir6.2, VDCC beta, and sarcoplasmic reticulum Ca(2+)-ATPase 3).
405	12438314	Conversely, genes normally suppressed in beta-cells, such as lactate dehydrogenase-A, hexokinase I, glucose-6-phosphatase, stress genes (heme oxygenase-1, A20, and Fas), and the transcription factor c-Myc, were markedly increased.
406	12453898	Whereas the loss of ATP-sensitive K(+) channel (K(ATP) channel) activity in human pancreatic beta-cells causes severe hypoglycemia in certain forms of hyperinsulinemic hypoglycemia, similar channel loss in sulfonylurea receptor-1 (SUR1) and Kir6.2 null mice yields a milder phenotype that is characterized by normoglycemia, unless the animals are stressed.
407	12453898	While investigating potential compensatory mechanisms, we found that incretins, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), can increase the cAMP content of Sur1KO islets but do not potentiate glucose-stimulated insulin release.
408	12453898	Potentiation does not appear to require cAMP-activated protein kinase (PKA) because H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) and KT5720, inhibitors of PKA, do not affect stimulation by GLP-1, GIP, or exendin-4 in wild-type islets, although they block phosphorylation of cAMP-response element-binding protein.
409	12453898	The impaired incretin response in Sur1KO islets is specific; the stimulation of insulin release by other modulators, including mastoparan and activators of protein kinase C, is conserved.
410	12540637	Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes.
411	12540637	The genes ABCC8 and KCNJ11, which encode the subunits sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) of the beta-cell ATP-sensitive potassium (K(ATP)) channel, control insulin secretion.
412	12540637	Common polymorphisms in these genes (ABCC8 exon 16-3t/c, exon 18 T/C, KCNJ11 E23K) have been variably associated with type 2 diabetes, but no large ( approximately 2,000 subjects) case-control studies have been performed.
413	12540637	Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes.
414	12540637	The genes ABCC8 and KCNJ11, which encode the subunits sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) of the beta-cell ATP-sensitive potassium (K(ATP)) channel, control insulin secretion.
415	12540637	Common polymorphisms in these genes (ABCC8 exon 16-3t/c, exon 18 T/C, KCNJ11 E23K) have been variably associated with type 2 diabetes, but no large ( approximately 2,000 subjects) case-control studies have been performed.
416	12540637	Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes.
417	12540637	The genes ABCC8 and KCNJ11, which encode the subunits sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) of the beta-cell ATP-sensitive potassium (K(ATP)) channel, control insulin secretion.
418	12540637	Common polymorphisms in these genes (ABCC8 exon 16-3t/c, exon 18 T/C, KCNJ11 E23K) have been variably associated with type 2 diabetes, but no large ( approximately 2,000 subjects) case-control studies have been performed.
419	12540638	The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes.
420	12540638	The E23K polymorphism of the pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channel subunit Kir6.2 (KCNJ11) is associated with type 2 diabetes in whites, and a recent in vitro study of the E23K variant suggests that the association to diabetes might be explained by a slight inhibition of serum insulin release.
421	12540638	The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes.
422	12540638	The E23K polymorphism of the pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channel subunit Kir6.2 (KCNJ11) is associated with type 2 diabetes in whites, and a recent in vitro study of the E23K variant suggests that the association to diabetes might be explained by a slight inhibition of serum insulin release.
423	12565699	The K(ATP) channel is a hetero-octamer comprising two subunits: the pore-forming subunit Kir6.x (Kir6.1 or Kir6.2) and the regulatory subunit sulfonylurea receptor SUR (SUR1 or SUR2).
424	12565699	Heterologous expression of differing combinations of Kir6.1 or Kir6.2 and SUR1 or SUR2 variant (SUR2A or SUR2B) reconstitute different types of K(ATP) channels with distinct electrophysiological properties and nucleotide and pharmacological sensitivities corresponding to the various K(ATP) channels in native tissues.
425	12565699	The K(ATP) channel is a hetero-octamer comprising two subunits: the pore-forming subunit Kir6.x (Kir6.1 or Kir6.2) and the regulatory subunit sulfonylurea receptor SUR (SUR1 or SUR2).
426	12565699	Heterologous expression of differing combinations of Kir6.1 or Kir6.2 and SUR1 or SUR2 variant (SUR2A or SUR2B) reconstitute different types of K(ATP) channels with distinct electrophysiological properties and nucleotide and pharmacological sensitivities corresponding to the various K(ATP) channels in native tissues.
427	12623161	They contain two different structural subunits: an inwardly rectifying potassium channel subunit (Kir6.x) and a sulfonylurea receptor (SURX).
428	12623161	Kir6.2/SUR1 has a pivotal role in pancreatic insulin secretion.
429	12623161	Kir6.1 knockout mice exhibit sudden cardiac death due to cardiac ischemia, indicating that Kir6.1 rather than Kir6.2 is critical in the regulation of vascular tone.
430	12623161	This article summarizes current understanding of the physiology and pathophysiology of Kir6.1- and Kir6.2-containing K(ATP) channels.
431	12623161	They contain two different structural subunits: an inwardly rectifying potassium channel subunit (Kir6.x) and a sulfonylurea receptor (SURX).
432	12623161	Kir6.2/SUR1 has a pivotal role in pancreatic insulin secretion.
433	12623161	Kir6.1 knockout mice exhibit sudden cardiac death due to cardiac ischemia, indicating that Kir6.1 rather than Kir6.2 is critical in the regulation of vascular tone.
434	12623161	This article summarizes current understanding of the physiology and pathophysiology of Kir6.1- and Kir6.2-containing K(ATP) channels.
435	12623161	They contain two different structural subunits: an inwardly rectifying potassium channel subunit (Kir6.x) and a sulfonylurea receptor (SURX).
436	12623161	Kir6.2/SUR1 has a pivotal role in pancreatic insulin secretion.
437	12623161	Kir6.1 knockout mice exhibit sudden cardiac death due to cardiac ischemia, indicating that Kir6.1 rather than Kir6.2 is critical in the regulation of vascular tone.
438	12623161	This article summarizes current understanding of the physiology and pathophysiology of Kir6.1- and Kir6.2-containing K(ATP) channels.
439	12826653	K(ATP) channels are hetero-octameric proteins composed of the pore-forming subunits Kir6.x (Kir6.1 or Kir6.2) of the inwardly rectifying K(+) channel family and the regulatory subunits SURx (SUR1, SUR2A or SUR2B), the receptor of the sulphonylureas widely used in treatment of type 2 diabetes mellitus.
440	12826653	Our studies of Kir6.2 null (knockout) and Kir6.1 null mice have shown that K(ATP) channels are critical metabolic sensors in protection against acute metabolic stress such as hyperglycaemia, hypoglycaemia, ischaemia and hypoxia.
441	12826653	K(ATP) channels are hetero-octameric proteins composed of the pore-forming subunits Kir6.x (Kir6.1 or Kir6.2) of the inwardly rectifying K(+) channel family and the regulatory subunits SURx (SUR1, SUR2A or SUR2B), the receptor of the sulphonylureas widely used in treatment of type 2 diabetes mellitus.
442	12826653	Our studies of Kir6.2 null (knockout) and Kir6.1 null mice have shown that K(ATP) channels are critical metabolic sensors in protection against acute metabolic stress such as hyperglycaemia, hypoglycaemia, ischaemia and hypoxia.
443	12941782	Recessive mutations of sulfonylurea receptor 1 (SUR1) and potassium inward rectifier 6.2 (Kir6.2), the two adjacent genes on chromosome 11p that comprise the beta-cell plasma membrane ATP-sensitive K(+) (K(ATP)) channels, are responsible for the most common form of congenital hyperinsulinism in children.
444	14514634	NN414, a SUR1/Kir6.2-selective potassium channel opener, reduces blood glucose and improves glucose tolerance in the VDF Zucker rat.
445	14514634	A novel potassium channel opener compound, NN414, selective for the SUR1/Kir6.2 subtype of the ATP-sensitive potassium channel, was used to examine the effect of reducing beta-cell workload in the male Vancouver diabetic fatty (VDF) Zucker rat model of mild type 2 diabetes.
446	14514634	NN414, a SUR1/Kir6.2-selective potassium channel opener, reduces blood glucose and improves glucose tolerance in the VDF Zucker rat.
447	14514634	A novel potassium channel opener compound, NN414, selective for the SUR1/Kir6.2 subtype of the ATP-sensitive potassium channel, was used to examine the effect of reducing beta-cell workload in the male Vancouver diabetic fatty (VDF) Zucker rat model of mild type 2 diabetes.
448	14514649	Patch-clamp experiments were performed on inside-out patches containing recombinant KATP channels (Kir6.2/SUR1) to record macroscopic currents.
449	14514649	The observed increase in KATP channel activity may result in multiple defects in glucose homeostasis, including impaired insulin and glucagon-like peptide-1 secretion and increased glucagon release.
450	14551916	Polymorphisms in five of 15 genes (33%) encoding molecules known to primarily influence pancreatic beta-cell function-ABCC8 (sulphonylurea receptor), KCNJ11 (KIR6.2), SLC2A2 (GLUT2), HNF4A (HNF4alpha), and INS (insulin)-significantly altered disease risk, and in three genes, the risk allele, haplotype, or both had a biologically consistent effect on a relevant physiological trait in the QT study.
451	14551916	We examined 35 genes predicted to have their major influence on insulin action, and three (9%)-INSR, PIK3R1, and SOS1-showed significant associations with diabetes.
452	14693719	Inappropriately elevated insulin secretion is the hallmark of persistent hyperinsulinemic hypoglycemia of infancy (PHHI), also denoted congenital hyperinsulinism.
453	14693719	By the genetic explanation of our family's cases of severe hypoglycemia, it is now clear that recessively inherited SCHAD deficiency can result in PHHI.
454	14693719	Inappropriately elevated insulin secretion is the hallmark of persistent hyperinsulinemic hypoglycemia of infancy (PHHI), also denoted congenital hyperinsulinism.
455	14693719	By the genetic explanation of our family's cases of severe hypoglycemia, it is now clear that recessively inherited SCHAD deficiency can result in PHHI.
456	14694850	Major break-throughs in the genetic sciences of type 2 diabetes have been identifications of insulin receptor gene mutations in syndromes of severe insulin resistance and mutations in pancreatic beta-cell genes in the monogenic sub-group of type 2 diabetes: maturity-onset-diabetes-of-the-young, MODY.
457	14694850	The studies reported in this thesis are excerpts from an extensive strategy of genetically dissecting (mutation analysis) in: 1) patients with the common form of late-onset type 2 diabetes mellitus the pathways that transduce the insulin signals from the plasma membrane to the activation of glycogen synthesis in skeletal muscle, and in 2) patients with either late-onset type diabetes or MODY the pathways involved in normal beta-cell development and beta-cell function (insulin secretion).
458	14694850	We could not confirm that a Val985Met variant in the insulin receptor is associated with type 2 diabetes or that the Met326Val of the p85 alpha regulatory subunit of the phosphoinositide-3 kinase is associated with insulin resistance.
459	14694850	We found no coding mutations (missense) in the insulin signalling protein kinases but we confirmed that the 5 bp deletion (PP1ARE) in the 3'-end of the PPP1R3 gene that encodes the glycogen-associated regulatory subunit of protein phosphatase-1 (PP1G) is associated with insulin resistance estimated as insulin mediated glucose uptake.
460	14694850	In contrast to protein kinases in skeletal muscles the genes encoding beta-cell transcription factors (IPF-1, NeuroD1/BETA2, and Neurogenin 3) are polymorphic but we could not confirm that the Asp76Asn of IPF-1 is a susceptibility gene for late-onset type 2 diabetes.
461	14694850	On the other hand we confirmed that the Ala45Thr variant in NeuroD1/BETA2 may represent a susceptibility gene for type 1 diabetes but none of these genes revealed any MODY-specific mutations.
462	14694850	Also the gene encoding the ATP-regulatable potassium channels of the beta-cell (Kir6.2) is polymorphic but none of these polymorphisms associated with changes in glucose-induced insulin secretion.
463	14707124	The pancreatic ATP-sensitive potassium (K(ATP)) channel, a complex of four sulfonylurea receptor 1 (SUR1) and four potassium channel Kir6.2 subunits, regulates insulin secretion by linking metabolic changes to beta-cell membrane potential.
464	14707124	Importantly, both mutant channels rescued to the cell surface have normal ATP, MgADP, and diazoxide sensitivities, demonstrating that SUR1 harboring either the A116P or the V187D mutation is capable of associating with Kir6.2 to form functional K(ATP) channels.
465	14707124	The pancreatic ATP-sensitive potassium (K(ATP)) channel, a complex of four sulfonylurea receptor 1 (SUR1) and four potassium channel Kir6.2 subunits, regulates insulin secretion by linking metabolic changes to beta-cell membrane potential.
466	14707124	Importantly, both mutant channels rescued to the cell surface have normal ATP, MgADP, and diazoxide sensitivities, demonstrating that SUR1 harboring either the A116P or the V187D mutation is capable of associating with Kir6.2 to form functional K(ATP) channels.
467	14722160	Progress in gene identification for more common, multifactorial forms of type 2 diabetes has been slower, but there is now compelling evidence that common variants in the PPARG, KCNJ11 and CAPN10 genes influence T2D-susceptibility, and positional cloning efforts within replicated regions of linkage promise to deliver additional components of inherited susceptibility.
468	14737020	The mRNA expression levels of Kir2.1, Kir3.1, Kir6.1, Kir6.2, and sulfonylurea receptor (SUR) 2A and 2B subunits in heart and aortal smooth muscles were determined by the reverse-transcription polymerase chain reaction.
469	14737020	However, there are no significant expression changes of Kir2.1, Kir3.1, Kir6.1, and Kir6.2 in diabetic rats.
470	14737020	The mRNA expression levels of Kir2.1, Kir3.1, Kir6.1, Kir6.2, and sulfonylurea receptor (SUR) 2A and 2B subunits in heart and aortal smooth muscles were determined by the reverse-transcription polymerase chain reaction.
471	14737020	However, there are no significant expression changes of Kir2.1, Kir3.1, Kir6.1, and Kir6.2 in diabetic rats.
472	14764798	Induction of beta-cell rest by a Kir6.2/SUR1-selective K(ATP)-channel opener preserves beta-cell insulin stores and insulin secretion in human islets cultured at high (11 mM) glucose.
473	14988278	Analysis of the type 2 diabetes-associated single nucleotide polymorphisms in the genes IRS1, KCNJ11, and PPARG2 in type 1 diabetes.
474	14988278	We have genotyped three single nucleotide polymorphisms associated with type 2 diabetes in a large type 1 diabetic family collection of European descent: Gly972Arg in the insulin receptor substrate 1 (IRS1) gene, Glu23Lys in the potassium inwardly-rectifying channel gene (KCNJ11), and Pro12Ala in the peroxisome proliferative-activated receptor gamma2 gene (PPARG2).
475	14988278	Analysis of the type 2 diabetes-associated single nucleotide polymorphisms in the genes IRS1, KCNJ11, and PPARG2 in type 1 diabetes.
476	14988278	We have genotyped three single nucleotide polymorphisms associated with type 2 diabetes in a large type 1 diabetic family collection of European descent: Gly972Arg in the insulin receptor substrate 1 (IRS1) gene, Glu23Lys in the potassium inwardly-rectifying channel gene (KCNJ11), and Pro12Ala in the peroxisome proliferative-activated receptor gamma2 gene (PPARG2).
477	15047618	Regulated expression of pdx-1 promotes in vitro differentiation of insulin-producing cells from embryonic stem cells.
478	15047618	The results showed that pdx-1 expression clearly enhanced the expression of the insulin 2, somatostatin, Kir6.2, glucokinase, neurogenin3, p48, Pax6, PC2, and HNF6 genes in the resulting differentiated cells.
479	15047618	Thus, exogenous expression of pdx-1 should provide a promising approach for efficiently producing insulin-secreting cells from human ES cells for future therapeutic use in diabetic patients.
480	15082027	Clonal insulin-secreting BRIN-BD11 cells were used to examine effects of chronic 72-144 h exposure to the sulphonylureas tolbutamide and glibenclamide on insulin release, cellular insulin content, and mRNA levels of the Kir6.2 and SUR1 subunits of the beta-cell K(ATP) channel.
481	15082027	Chronic exposure to tolbutamide or glibenclamide had no effect upon transcription of the Kir6.2 or SUR1 subunits of the pancreatic beta-cell K(ATP) channel.
482	15082027	Clonal insulin-secreting BRIN-BD11 cells were used to examine effects of chronic 72-144 h exposure to the sulphonylureas tolbutamide and glibenclamide on insulin release, cellular insulin content, and mRNA levels of the Kir6.2 and SUR1 subunits of the beta-cell K(ATP) channel.
483	15082027	Chronic exposure to tolbutamide or glibenclamide had no effect upon transcription of the Kir6.2 or SUR1 subunits of the pancreatic beta-cell K(ATP) channel.
484	15111507	The genes for the sulfonylurea receptor (SUR1; encoded by ABCC8) and its associated islet ATP-sensitive potassium channel (Kir6.2; encoded by KCNJ11) are adjacent to one another on human chromosome 11.
485	15111507	We find that the E23K variant in Kir6.2 demonstrates very strong allelic association with a coding variant (A1369S) in the neighboring SUR1 gene (r(2) > 0.9) across a range of population samples, making it difficult to distinguish which gene and polymorphism in this region are most likely responsible for the reported association.
486	15111507	Like peroxisome proliferator-activated receptor gamma, the SUR1/Kir6.2 gene region both contributes to the inherited risk of type 2 diabetes and encodes proteins that are targets for hypoglycemic medications, providing an intriguing link between the underlying mechanism of disease and validated targets for pharmacological treatment.
487	15111507	The genes for the sulfonylurea receptor (SUR1; encoded by ABCC8) and its associated islet ATP-sensitive potassium channel (Kir6.2; encoded by KCNJ11) are adjacent to one another on human chromosome 11.
488	15111507	We find that the E23K variant in Kir6.2 demonstrates very strong allelic association with a coding variant (A1369S) in the neighboring SUR1 gene (r(2) > 0.9) across a range of population samples, making it difficult to distinguish which gene and polymorphism in this region are most likely responsible for the reported association.
489	15111507	Like peroxisome proliferator-activated receptor gamma, the SUR1/Kir6.2 gene region both contributes to the inherited risk of type 2 diabetes and encodes proteins that are targets for hypoglycemic medications, providing an intriguing link between the underlying mechanism of disease and validated targets for pharmacological treatment.
490	15111507	The genes for the sulfonylurea receptor (SUR1; encoded by ABCC8) and its associated islet ATP-sensitive potassium channel (Kir6.2; encoded by KCNJ11) are adjacent to one another on human chromosome 11.
491	15111507	We find that the E23K variant in Kir6.2 demonstrates very strong allelic association with a coding variant (A1369S) in the neighboring SUR1 gene (r(2) > 0.9) across a range of population samples, making it difficult to distinguish which gene and polymorphism in this region are most likely responsible for the reported association.
492	15111507	Like peroxisome proliferator-activated receptor gamma, the SUR1/Kir6.2 gene region both contributes to the inherited risk of type 2 diabetes and encodes proteins that are targets for hypoglycemic medications, providing an intriguing link between the underlying mechanism of disease and validated targets for pharmacological treatment.
493	15115830	Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.
494	15127139	[3T3-L1 adipocytes reduces Kir6.2 channel expression in MIN6 insulin-secreting cells in vitro].
495	15127139	The results showed that the Kir6.2 cDNA levels corrected by GAPDH cDNA levels after densitometric analysis were 0.989+/-0.035 in control group and 0.726+/-0.087 in coculture group.
496	15127139	[3T3-L1 adipocytes reduces Kir6.2 channel expression in MIN6 insulin-secreting cells in vitro].
497	15127139	The results showed that the Kir6.2 cDNA levels corrected by GAPDH cDNA levels after densitometric analysis were 0.989+/-0.035 in control group and 0.726+/-0.087 in coculture group.
498	15180566	Deficient insulin release causes hyperglycemia and diabetes, whereas excessive insulin release can give rise to serious metabolic disorders, such as nesidioblastosis (Persistent Hyperinsulinemic Hypoglycemia of Infancy, PHHI) and might also be closely associated with development of type 2 diabetes and obesity.
499	15180566	Thus, insulin release is regulated by e.g. somatostatin receptors, GLP-1 receptors, muscarinic receptors, cholecystokinin receptors and adrenergic receptors.
500	15220194	Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets.
501	15220194	Therefore, we studied the effect of diazoxide and of the novel potassium channel opener NN414, selective for the beta-cell potassium channel SUR1/Kir6.2, on glucose- and IL-1beta-induced apoptosis and impaired function in human beta-cells.
502	15220194	Exposure of human islets for 4 days to 11.1 and 33.3 mmol/l glucose, 2 ng/ml IL-1beta, or 10 and 100 micromol/l of the sulfonylurea tolbutamide induced beta-cell apoptosis and impaired glucose-stimulated insulin secretion.
503	15220194	By Western blotting with phosphospecific antibodies, glucose and IL-1beta were shown to activate the extracellular signal-regulated kinase (ERK) 1/2, an effect that was abrogated by 3 micromol/l NN414.
504	15220194	Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets.
505	15220194	Therefore, we studied the effect of diazoxide and of the novel potassium channel opener NN414, selective for the beta-cell potassium channel SUR1/Kir6.2, on glucose- and IL-1beta-induced apoptosis and impaired function in human beta-cells.
506	15220194	Exposure of human islets for 4 days to 11.1 and 33.3 mmol/l glucose, 2 ng/ml IL-1beta, or 10 and 100 micromol/l of the sulfonylurea tolbutamide induced beta-cell apoptosis and impaired glucose-stimulated insulin secretion.
507	15220194	By Western blotting with phosphospecific antibodies, glucose and IL-1beta were shown to activate the extracellular signal-regulated kinase (ERK) 1/2, an effect that was abrogated by 3 micromol/l NN414.
508	15292032	Neither of the two protocols affected gene expression of the ion channel-associated proteins Kir6.2, sulfonylurea receptor 1, voltage-dependent calcium channel-alpha1, or Kv2.1.
509	15314688	Foxa2 regulates multiple pathways of insulin secretion.
510	15314688	The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
511	15314688	The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells.
512	15314688	Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion.
513	15314688	Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent.
514	15314688	Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans.
515	15314688	Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets.
516	15314688	Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion.
517	15314688	Foxa2 regulates multiple pathways of insulin secretion.
518	15314688	The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
519	15314688	The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells.
520	15314688	Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion.
521	15314688	Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent.
522	15314688	Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans.
523	15314688	Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets.
524	15314688	Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion.
525	15314688	Foxa2 regulates multiple pathways of insulin secretion.
526	15314688	The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
527	15314688	The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells.
528	15314688	Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion.
529	15314688	Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent.
530	15314688	Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans.
531	15314688	Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets.
532	15314688	Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion.
533	15314688	Foxa2 regulates multiple pathways of insulin secretion.
534	15314688	The regulation of insulin secretion by pancreatic beta cells is perturbed in several diseases, including adult-onset (type 2) diabetes and persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
535	15314688	The first mouse model for PHHI has a conditional deletion of the gene encoding the winged-helix transcription factor Foxa2 (Forkhead box a2, formerly Hepatocyte nuclear factor 3beta) in pancreatic beta cells.
536	15314688	Using isolated islets, we found that Foxa2 deficiency resulted in excessive insulin release in response to amino acids and complete loss of glucose-stimulated insulin secretion.
537	15314688	Most PHHI cases are associated with mutations in SUR1 (Sulfonylurea receptor 1) or KIR6.2 (Inward rectifier K(+) channel member 6.2), which encode the subunits of the ATP-sensitive K(+) channel, and RNA in situ hybridization of mutant mouse islets revealed that expression of both genes is Foxa2 dependent.
538	15314688	Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans.
539	15314688	Hadhsc is a direct target of Foxa2, as demonstrated by cotransfection as well as in vivo chromatin immunoprecipitation experiments using isolated islets.
540	15314688	Thus, we have established Foxa2 as an essential activator of genes that function in multiple pathways governing insulin secretion.
541	15448106	Permanent neonatal diabetes (PND) can be caused by mutations in the transcription factors insulin promoter factor (IPF)-1, eukaryotic translation initiation factor-2alpha kinase 3 (EIF2AK3), and forkhead box-P3 and in key components of insulin secretion: glucokinase (GCK) and the ATP-sensitive K(+) channel subunit Kir6.2.
542	15448106	We sequenced the gene encoding Kir6.2 (KCNJ11) in 11 probands with GCK-negative PND.
543	15448106	Apparently insulin-dependent patients with mutations in Kir6.2 may be managed on an oral sulfonylurea with sustained metabolic control rather than insulin injections, illustrating the principle of pharmacogenetics applied in diabetes treatment.
544	15448106	Permanent neonatal diabetes (PND) can be caused by mutations in the transcription factors insulin promoter factor (IPF)-1, eukaryotic translation initiation factor-2alpha kinase 3 (EIF2AK3), and forkhead box-P3 and in key components of insulin secretion: glucokinase (GCK) and the ATP-sensitive K(+) channel subunit Kir6.2.
545	15448106	We sequenced the gene encoding Kir6.2 (KCNJ11) in 11 probands with GCK-negative PND.
546	15448106	Apparently insulin-dependent patients with mutations in Kir6.2 may be managed on an oral sulfonylurea with sustained metabolic control rather than insulin injections, illustrating the principle of pharmacogenetics applied in diabetes treatment.
547	15448106	Permanent neonatal diabetes (PND) can be caused by mutations in the transcription factors insulin promoter factor (IPF)-1, eukaryotic translation initiation factor-2alpha kinase 3 (EIF2AK3), and forkhead box-P3 and in key components of insulin secretion: glucokinase (GCK) and the ATP-sensitive K(+) channel subunit Kir6.2.
548	15448106	We sequenced the gene encoding Kir6.2 (KCNJ11) in 11 probands with GCK-negative PND.
549	15448106	Apparently insulin-dependent patients with mutations in Kir6.2 may be managed on an oral sulfonylurea with sustained metabolic control rather than insulin injections, illustrating the principle of pharmacogenetics applied in diabetes treatment.
550	15448107	It has very recently been shown that heterozygous activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive K(+) channel involved in the regulation of insulin secretion, cause PND.
551	15448107	Although Kir6.2 mutation carriers do not represent a phenotypically specific form of PND, an impaired function of Kir6.2 is associated with in utero insulin secretory insufficiency and growth retardation.
552	15448107	It has very recently been shown that heterozygous activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive K(+) channel involved in the regulation of insulin secretion, cause PND.
553	15448107	Although Kir6.2 mutation carriers do not represent a phenotypically specific form of PND, an impaired function of Kir6.2 is associated with in utero insulin secretory insufficiency and growth retardation.
554	15467258	In studies of various cloned K(ATP) channels, mitiglinide shows a higher selectivity for the beta-cell type of SUR1/Kir6.2 than the cardiac and smooth muscle types of K(ATP) channels in comparison with glibenclamide and glimepiride.
555	15504956	Moreover, HGE neurons were also present in ARC of Kir6.2 null mice.
556	15531505	Recently, activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 were identified in 10 PNDM patients.
557	15531505	This study demonstrates the feasibility of oral sulfonylurea treatment in PNDM patients with Kir6.2 mutations even during infancy, and the superiority of this approach over insulin administration.
558	15531505	Recently, activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 were identified in 10 PNDM patients.
559	15531505	This study demonstrates the feasibility of oral sulfonylurea treatment in PNDM patients with Kir6.2 mutations even during infancy, and the superiority of this approach over insulin administration.
560	15533888	We studied the effects of haloperidol on native ATP-sensitive potassium (K(ATP)) channels in mouse pancreatic beta cells and on cloned Kir6.2/SUR1 channels expressed in HEK293 cells.
561	15533888	Haloperidol blocked cloned Kir6.2/SUR1 and Kir6.2DeltaC36 K(ATP) channels expressed in HEK cells.
562	15533888	We studied the effects of haloperidol on native ATP-sensitive potassium (K(ATP)) channels in mouse pancreatic beta cells and on cloned Kir6.2/SUR1 channels expressed in HEK293 cells.
563	15533888	Haloperidol blocked cloned Kir6.2/SUR1 and Kir6.2DeltaC36 K(ATP) channels expressed in HEK cells.
564	15561897	The adjacent cytoplasmic L0 linker serves a dual function, acting as a tether to link the MDR-like core to the KIR6.2/TMD0 complex and exerting bidirectional control over channel gating via interactions with the NH2-terminus of the KIR.
565	15561897	Elements of the COOH-terminal half of the core recognize a hydrophobic group in glibenclamide, adjacent to the sulfonylurea moiety, to provide selectivity for SUR1, while the benzamido group appears to be in proximity to L0 and the KIR NH2-terminus.
566	15561899	It is comprised of sulfonylurea receptor (SUR)-1 and Kir6.2 proteins.
567	15561899	Binding of Mg nucleotides to the nucleotide-binding domains (NBDs) of SUR1 stimulates channel opening and leads to membrane hyperpolarization and inhibition of insulin secretion.
568	15561899	To elucidate the structural basis of this regulation, we constructed a molecular model of the NBDs of SUR1, based on the crystal structures of mammalian proteins that belong to the same family of ATP-binding cassette transporter proteins.
569	15561907	Formed through association of the Kir6.2 pore and the sulfonylurea receptor, the stress-responsive ATP-sensitive K(+) channels (K(ATP) channels), with their metabolic-sensing capability and broad tissue expression, are potential candidates for integrating the systemic adaptive response to repetitive exercise.
570	15561908	Analysis of Kir6.2 null mice has shown that Kir6.2/SUR1 channels in pancreatic beta-cells and the hypothalamus are essential in glucose-induced insulin secretion and hypoglycemia-induced glucagon secretion, respectively, and that Kir6.2/SUR2 channels are involved in glucose uptake in skeletal muscles.
571	15561908	Our studies of Kir6.2 null and Kir6.1 null mice reveal that KATP channels are critical metabolic sensors in acute metabolic changes, including hyperglycemia, hypoglycemia, ischemia, and hypoxia.
572	15561908	Analysis of Kir6.2 null mice has shown that Kir6.2/SUR1 channels in pancreatic beta-cells and the hypothalamus are essential in glucose-induced insulin secretion and hypoglycemia-induced glucagon secretion, respectively, and that Kir6.2/SUR2 channels are involved in glucose uptake in skeletal muscles.
573	15561908	Our studies of Kir6.2 null and Kir6.1 null mice reveal that KATP channels are critical metabolic sensors in acute metabolic changes, including hyperglycemia, hypoglycemia, ischemia, and hypoxia.
574	15561946	Partial suppression of beta-cell K(ATP) channels in transgenic (AAA) mice causes hypersecretion of insulin and enhanced glucose tolerance, whereas complete suppression of these channels in Kir6.2 knockout (KO) mice leads to hyperexcitability, but mild glucose intolerance.
575	15561965	In contrast, the well-documented associations of peroxisome proliferator-activated receptor gamma P12A and Kir6.2 E23K with type 2 diabetes are both robustly observed in these 9,000 subjects, including an additional (previously unpublished) confirmation of Kir6.2 E23K and type 2 diabetes in the Polish and North American samples (combined OR 1.15 [1.05-1.26], P = 0.001).
576	15562009	Congenital hyperinsulinism (HI) is most commonly caused by recessive mutations of the pancreatic beta-cell ATP-sensitive potassium channel (K(ATP)), encoded by two genes on chromosome 11p, SUR1 and Kir6.2.
577	15562009	The two mutations that have been best studied, SUR1 g3992-9a and SUR1 delF1388, are null mutations yielding nonfunctional channels and are characterized by nonresponsiveness to diazoxide, a channel agonist, and absence of acute insulin responses (AIRs) to tolbutamide, a channel antagonist, or leucine.
578	15562009	To examine phenotypes of other K(ATP) mutations, we measured AIRs to calcium, leucine, glucose, and tolbutamide in infants with recessive SUR1 or Kir6.2 mutations expressed as diffuse HI (n = 8) or focal HI (n = 14).
579	15562009	Congenital hyperinsulinism (HI) is most commonly caused by recessive mutations of the pancreatic beta-cell ATP-sensitive potassium channel (K(ATP)), encoded by two genes on chromosome 11p, SUR1 and Kir6.2.
580	15562009	The two mutations that have been best studied, SUR1 g3992-9a and SUR1 delF1388, are null mutations yielding nonfunctional channels and are characterized by nonresponsiveness to diazoxide, a channel agonist, and absence of acute insulin responses (AIRs) to tolbutamide, a channel antagonist, or leucine.
581	15562009	To examine phenotypes of other K(ATP) mutations, we measured AIRs to calcium, leucine, glucose, and tolbutamide in infants with recessive SUR1 or Kir6.2 mutations expressed as diffuse HI (n = 8) or focal HI (n = 14).
582	15563985	K(ATP) channels are composed of pore-forming inwardly rectifying potassium channel (Kir6.2 or Kir6.1) subunits and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) subunits.
583	15563985	Kir6.2 or Kir6.1 subunits conjoined with a SUR subunit constitute the various tissue-specific K(ATP) channels with distinct pharmacological properties.
584	15563985	K(ATP) channels are composed of pore-forming inwardly rectifying potassium channel (Kir6.2 or Kir6.1) subunits and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) subunits.
585	15563985	Kir6.2 or Kir6.1 subunits conjoined with a SUR subunit constitute the various tissue-specific K(ATP) channels with distinct pharmacological properties.
586	15579791	Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes.
587	15579791	We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study.
588	15579791	Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004).
589	15579791	We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene.
590	15579791	Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes.
591	15579791	We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study.
592	15579791	Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004).
593	15579791	We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene.
594	15579791	Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes.
595	15579791	We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study.
596	15579791	Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004).
597	15579791	We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene.
598	15579791	Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes.
599	15579791	We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study.
600	15579791	Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004).
601	15579791	We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene.
602	15580558	We screened the KCNJ11 gene in 12 Italian patients with PNDM (onset within 3 months from birth) and in six patients with non-autoimmune, insulin-requiring diabetes diagnosed during the first year of life.
603	15580558	Permanent diabetes of non autoimmune origin can present up to 6 months from birth in individuals with KCNJ11 and EIF2AK3 mutations.
604	15580558	We screened the KCNJ11 gene in 12 Italian patients with PNDM (onset within 3 months from birth) and in six patients with non-autoimmune, insulin-requiring diabetes diagnosed during the first year of life.
605	15580558	Permanent diabetes of non autoimmune origin can present up to 6 months from birth in individuals with KCNJ11 and EIF2AK3 mutations.
606	15583126	To determine the molecular basis of these different phenotypes, we expressed wild-type or mutant (R201C, Q52R, or V59G) Kir6.2/sulfonylurea receptor 1 channels in Xenopus oocytes.
607	15630453	The abundance of mRNAs for Glut2 and HNF3beta was reduced in islets of betaPKClambda(-/-) mice, and the expression of genes regulated by HNF3beta was also affected (that of Sur1 and Kir6.2 genes was reduced, whereas that of hexokinase 1 and hexokinase 2 genes was increased).
608	15630453	Normalization of HNF3beta expression by infection of islets from betaPKClambda(-/-) mice with an adenoviral vector significantly reversed the defect in glucose-stimulated insulin secretion.
609	15631623	The three Fox (forkhead box) group A genes, Foxa1, Foxa2 and Foxa3, are expressed in embryonic endoderm, the germ layer that gives rise to the digestive system, and contribute to the specification of the pancreas and the regulation of glucose homoeostasis.
610	15631623	Deletion of the Foxa2 gene in pancreatic beta-cells in mice results in a phenotype resembling PHHI (persistent hyperinsulinaemic hypoglycaemia of infancy).
611	15631623	Molecular analyses have demonstrated that Foxa2 is an important regulator of the genes encoding Sur1, Kir6.2 and Schad (short chain L-3-hydroxyacyl-CoA dehydrogenase), mutation of which causes PHHI in humans.
612	15631623	An additional winged-helix protein, Foxo1, contributes to pancreatic beta-cell function by regulating the Pdx1 gene, which is required for pancreatic development in cooperation with Foxa2.
613	15631623	The three Fox (forkhead box) group A genes, Foxa1, Foxa2 and Foxa3, are expressed in embryonic endoderm, the germ layer that gives rise to the digestive system, and contribute to the specification of the pancreas and the regulation of glucose homoeostasis.
614	15631623	Deletion of the Foxa2 gene in pancreatic beta-cells in mice results in a phenotype resembling PHHI (persistent hyperinsulinaemic hypoglycaemia of infancy).
615	15631623	Molecular analyses have demonstrated that Foxa2 is an important regulator of the genes encoding Sur1, Kir6.2 and Schad (short chain L-3-hydroxyacyl-CoA dehydrogenase), mutation of which causes PHHI in humans.
616	15631623	An additional winged-helix protein, Foxo1, contributes to pancreatic beta-cell function by regulating the Pdx1 gene, which is required for pancreatic development in cooperation with Foxa2.
617	15652236	Role of two adjacent cytoplasmic tyrosine residues in MRP1 (ABCC1) transport activity and sensitivity to sulfonylureas.
618	15652236	The human ATP-binding cassette (ABC) protein MRP1 causes resistance to many anticancer drugs and is also a primary active transporter of conjugated metabolites and endogenous organic anions, including leukotriene C(4) (LTC(4)) and glutathione (GSH).
619	15652236	The sulfonylurea receptors SUR1 and SUR2 are related ABC proteins with the same domain structure as MRP1, but serve as regulators of the K(+) channel Kir6.2.
620	15652236	Despite their functional differences, the activity of both SUR1/2 and MRP1 can be blocked by glibenclamide, a sulfonylurea used to treat diabetes.
621	15652236	We have now investigated the effect of mutating Tyr(1189) and Tyr(1190) in the comparable region of MRP1 on its transport activity and sulfonylurea sensitivity.
622	15652236	Ala and Ser substitutions of Tyr(1189) and Tyr(1190) caused a > or =50% decrease in the ability of MRP1 to transport different organic anions, and a decrease in LTC(4) photolabeling.
623	15652236	We conclude that MRP1 Tyr(1189) and Tyr(1190), unlike the corresponding residues in SUR1, are not involved in its differential sensitivity to sulfonylureas, but nevertheless, may be involved in the transport activity of MRP1, especially with respect to GSH.
624	15671113	The fetal insulin hypothesis proposes that low birth weight might be mediated partly by genetic factors that impair insulin secretion/sensitivity during the fetal stage, as shown for glucokinase, the ATP-sensitive K+ channel subunit Kir6.2, and the small heterodimer partner genes.
625	15671113	Glutamic acid decarboxylase 2 gene (GAD2) overexpression impairs insulin secretion in animals.
626	15671113	In the present study, we investigated potential effects of the functional -243 A-->G polymorphism in the 5' promoter region of the GAD2 gene on fetal growth, insulin secretion, food intake, and risk of obesity in 635 French Caucasian severely obese children from three different medical centers.
627	15671113	These results confirm the association between GAD2-243 promoter SNP and the risk for obesity and suggest that GAD2 may be a polygenic component of the complex mechanisms linking birth weight to further risk for metabolic diseases, possibly involving the pleiotropic effect of insulin on fetal growth and later on feeding behavior.
628	15678092	We further explore how the binding properties of repaglinide and glibenclamide are affected by functional uncoupling of SUR1 and Kir6.2 in Kir6.2DeltaN14/SUR1 channels.
629	15678092	Glibenclamide, tolbutamide and nateglinide all bound with marginally lower affinity to SUR1 than to Kir6.2/SUR1. 3.
630	15678092	The results suggest that Kir6.2 causes a conformational change in SUR1 required for high-affinity repaglinide binding, or that the high-affinity repaglinide-binding site includes contributions from both SUR1 and Kir6.2.
631	15678092	We further explore how the binding properties of repaglinide and glibenclamide are affected by functional uncoupling of SUR1 and Kir6.2 in Kir6.2DeltaN14/SUR1 channels.
632	15678092	Glibenclamide, tolbutamide and nateglinide all bound with marginally lower affinity to SUR1 than to Kir6.2/SUR1. 3.
633	15678092	The results suggest that Kir6.2 causes a conformational change in SUR1 required for high-affinity repaglinide binding, or that the high-affinity repaglinide-binding site includes contributions from both SUR1 and Kir6.2.
634	15678092	We further explore how the binding properties of repaglinide and glibenclamide are affected by functional uncoupling of SUR1 and Kir6.2 in Kir6.2DeltaN14/SUR1 channels.
635	15678092	Glibenclamide, tolbutamide and nateglinide all bound with marginally lower affinity to SUR1 than to Kir6.2/SUR1. 3.
636	15678092	The results suggest that Kir6.2 causes a conformational change in SUR1 required for high-affinity repaglinide binding, or that the high-affinity repaglinide-binding site includes contributions from both SUR1 and Kir6.2.
637	15715885	Monogenic forms of diabetes (maturity-onset diabetes of the young, MODY) have been identified and classified into MODY1-6 according to the mutated genes that by being expressed in the pancreatic beta-cells confirm at the molecular level the clinical presentation of MODY as a predominantly insulin secretory deficient form of diabetes mellitus.
638	15715885	Mutation analyses of selected 'candidate' susceptibility genes in various populations have also identified the widespread Pro12Ala variant of the peroxisome proliferator-activated receptor-gamma and the common Glu23Lys variant of the ATP-sensitive potassium channel, Kir6.2 (KCNJ11).
639	15718250	Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes.
640	15735229	High-dose glibenclamide can replace insulin therapy despite transitory diarrhea in early-onset diabetes caused by a novel R201L Kir6.2 mutation.
641	15761495	The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion.
642	15761495	These phenotypes can be explained in part by a 60% reduction in expression of the potassium channel subunit Kir6.2.
643	15761495	We demonstrate using cotransfection assays that the Kir6.2 gene is a transcriptional target of HNF-4alpha.
644	15761495	Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel.
645	15761495	The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion.
646	15761495	These phenotypes can be explained in part by a 60% reduction in expression of the potassium channel subunit Kir6.2.
647	15761495	We demonstrate using cotransfection assays that the Kir6.2 gene is a transcriptional target of HNF-4alpha.
648	15761495	Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel.
649	15793244	Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility.
650	15793244	Glucose-induced insulin secretion from pancreatic beta-cells depends critically on ATP-sensitive K(+) channel (K(ATP) channel) activity, but it is not known whether K(ATP) channels are involved in the potentiation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP).
651	15793244	In mice lacking K(ATP) channels (Kir6.2(-/-) mice), we found that pretreatment with GIP in vivo failed to blunt the rise in blood glucose levels after oral glucose load.
652	15793244	In Kir6.2(-/-) mice, potentiation of insulin secretion by GIP in vivo was markedly attenuated, indicating that K(ATP) channels are essential in the insulinotropic effect of GIP.
653	15793244	In contrast, pretreatment with glucagon-like peptide-1 (GLP-1) in Kir6.2(-/-) mice potentiated insulin secretion and blunted the rise in blood glucose levels.
654	15793244	We also found that GLP-1 inhibited gut motility whereas GIP did not.
655	15793244	Perfusion experiments of Kir6.2(-/-) mice revealed severely impaired potentiation of insulin secretion by 1 nmol/l GIP and substantial potentiation by 1 nmol/l GLP-1.
656	15793244	Although both GIP and GLP-1 increase the intracellular cAMP concentration and potentiate insulin secretion, these results demonstrate that the GLP-1 and GIP signaling pathways involve the K(ATP) channel differently.
657	15793244	Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility.
658	15793244	Glucose-induced insulin secretion from pancreatic beta-cells depends critically on ATP-sensitive K(+) channel (K(ATP) channel) activity, but it is not known whether K(ATP) channels are involved in the potentiation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP).
659	15793244	In mice lacking K(ATP) channels (Kir6.2(-/-) mice), we found that pretreatment with GIP in vivo failed to blunt the rise in blood glucose levels after oral glucose load.
660	15793244	In Kir6.2(-/-) mice, potentiation of insulin secretion by GIP in vivo was markedly attenuated, indicating that K(ATP) channels are essential in the insulinotropic effect of GIP.
661	15793244	In contrast, pretreatment with glucagon-like peptide-1 (GLP-1) in Kir6.2(-/-) mice potentiated insulin secretion and blunted the rise in blood glucose levels.
662	15793244	We also found that GLP-1 inhibited gut motility whereas GIP did not.
663	15793244	Perfusion experiments of Kir6.2(-/-) mice revealed severely impaired potentiation of insulin secretion by 1 nmol/l GIP and substantial potentiation by 1 nmol/l GLP-1.
664	15793244	Although both GIP and GLP-1 increase the intracellular cAMP concentration and potentiate insulin secretion, these results demonstrate that the GLP-1 and GIP signaling pathways involve the K(ATP) channel differently.
665	15793244	Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility.
666	15793244	Glucose-induced insulin secretion from pancreatic beta-cells depends critically on ATP-sensitive K(+) channel (K(ATP) channel) activity, but it is not known whether K(ATP) channels are involved in the potentiation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP).
667	15793244	In mice lacking K(ATP) channels (Kir6.2(-/-) mice), we found that pretreatment with GIP in vivo failed to blunt the rise in blood glucose levels after oral glucose load.
668	15793244	In Kir6.2(-/-) mice, potentiation of insulin secretion by GIP in vivo was markedly attenuated, indicating that K(ATP) channels are essential in the insulinotropic effect of GIP.
669	15793244	In contrast, pretreatment with glucagon-like peptide-1 (GLP-1) in Kir6.2(-/-) mice potentiated insulin secretion and blunted the rise in blood glucose levels.
670	15793244	We also found that GLP-1 inhibited gut motility whereas GIP did not.
671	15793244	Perfusion experiments of Kir6.2(-/-) mice revealed severely impaired potentiation of insulin secretion by 1 nmol/l GIP and substantial potentiation by 1 nmol/l GLP-1.
672	15793244	Although both GIP and GLP-1 increase the intracellular cAMP concentration and potentiate insulin secretion, these results demonstrate that the GLP-1 and GIP signaling pathways involve the K(ATP) channel differently.
673	15793244	Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility.
674	15793244	Glucose-induced insulin secretion from pancreatic beta-cells depends critically on ATP-sensitive K(+) channel (K(ATP) channel) activity, but it is not known whether K(ATP) channels are involved in the potentiation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP).
675	15793244	In mice lacking K(ATP) channels (Kir6.2(-/-) mice), we found that pretreatment with GIP in vivo failed to blunt the rise in blood glucose levels after oral glucose load.
676	15793244	In Kir6.2(-/-) mice, potentiation of insulin secretion by GIP in vivo was markedly attenuated, indicating that K(ATP) channels are essential in the insulinotropic effect of GIP.
677	15793244	In contrast, pretreatment with glucagon-like peptide-1 (GLP-1) in Kir6.2(-/-) mice potentiated insulin secretion and blunted the rise in blood glucose levels.
678	15793244	We also found that GLP-1 inhibited gut motility whereas GIP did not.
679	15793244	Perfusion experiments of Kir6.2(-/-) mice revealed severely impaired potentiation of insulin secretion by 1 nmol/l GIP and substantial potentiation by 1 nmol/l GLP-1.
680	15793244	Although both GIP and GLP-1 increase the intracellular cAMP concentration and potentiate insulin secretion, these results demonstrate that the GLP-1 and GIP signaling pathways involve the K(ATP) channel differently.
681	15797964	Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes.
682	15842514	Common variants in the ATP-sensitive K+ channel genes KCNJ11 (Kir6.2) and ABCC8 (SUR1) in relation to glucose intolerance: population-based studies and meta-analyses.
683	15864298	We investigated the functional effects of the I296L mutation by expressing wild-type or mutant Kir6.2/SUR1 channels in Xenopus oocytes.
684	15893323	K(ATP) channels generated from coexpression of Kir6.2 with SUR1 exhibit greater MgADP stimulation than channels generated from coexpression of Kir6.2 with SUR2A.
685	15910877	Gain-of-function mutations in Kir6.2 cause permanent neonatal diabetes mellitus (PNDM) by reducing the ATP sensitivity of the K(ATP) channel and increasing the K(ATP) current, which is predicted to inhibit beta-cell electrical activity and insulin secretion.
686	15912330	To date, only a few susceptibility genes have been identified (such as PPARG, KCNJ11, CAPN10).
687	15962003	ATP-sensitive K(+) (K(ATP)) channels, comprised of pore-forming Kir6.2 and regulatory SUR1 subunits, play a critical role in regulating insulin secretion.
688	15962003	Binding of ATP to Kir6.2 inhibits, whereas interaction of MgATP with SUR1 activates, K(ATP) channels.
689	15962003	Both mutations also altered Kir6.2/SUR1 interactions, enhancing the stimulatory effect of MgATP (which is mediated via SUR1).
690	15962003	ATP-sensitive K(+) (K(ATP)) channels, comprised of pore-forming Kir6.2 and regulatory SUR1 subunits, play a critical role in regulating insulin secretion.
691	15962003	Binding of ATP to Kir6.2 inhibits, whereas interaction of MgATP with SUR1 activates, K(ATP) channels.
692	15962003	Both mutations also altered Kir6.2/SUR1 interactions, enhancing the stimulatory effect of MgATP (which is mediated via SUR1).
693	15962003	ATP-sensitive K(+) (K(ATP)) channels, comprised of pore-forming Kir6.2 and regulatory SUR1 subunits, play a critical role in regulating insulin secretion.
694	15962003	Binding of ATP to Kir6.2 inhibits, whereas interaction of MgATP with SUR1 activates, K(ATP) channels.
695	15962003	Both mutations also altered Kir6.2/SUR1 interactions, enhancing the stimulatory effect of MgATP (which is mediated via SUR1).
696	15963039	K(ATP) channels are hetero-octameric complexes comprising two subunits Kir6.2 and sulfonylurea receptor 1 (SUR1).
697	15963039	On the other hand, now there is evidence of an association between polymorphisms in the Kir6.2 gene and type 2 diabetes mellitus, mutations in the Kir6.2 gene and neonatal diabetes mellitus, and mutations in the SUR1 gene and diabetes mellitus.
698	15963039	K(ATP) channels are hetero-octameric complexes comprising two subunits Kir6.2 and sulfonylurea receptor 1 (SUR1).
699	15963039	On the other hand, now there is evidence of an association between polymorphisms in the Kir6.2 gene and type 2 diabetes mellitus, mutations in the Kir6.2 gene and neonatal diabetes mellitus, and mutations in the SUR1 gene and diabetes mellitus.
700	15980413	In this study, we show that in contrast to their stimulatory effect on K(ATP) channels, LC-CoA (e.g. oleoyl-CoA) potently and reversibly inhibits all other Kir channels tested (Kir1.1, Kir2.1, Kir3.4, Kir7.1).
701	15980413	Biochemical studies also demonstrate that PIP2 and LC-CoA bind with similar affinity to the C-terminal domains of Kir2.1 and Kir6.2 and that PIP2 binding can be competitively antagonized by LC-CoA, suggesting that the mechanism of LC-CoA inhibition involves displacement of PIP2.
702	15980413	Furthermore, we demonstrate that in contrast to its stimulatory effect on K(ATP) channels, phosphatidylinositol 3,4-bisphosphate has an inhibitory effect on Kir1.1 and Kir2.1.
703	16123353	The prediction that overactivity of the pancreatic ATP-sensitive K(+) channel (K(ATP) channel) underlies reduced insulin secretion and causes a diabetic phenotype in humans has recently been borne out by genetic studies implicating "activating" mutations in the Kir6.2 subunit of K(ATP) as causal in both permanent and transient neonatal diabetes.
704	16142506	Therefore, the effects of the Glu23Lys polymorphism in the KCNJ11 (KIR6.2) gene (potassium inwardly rectifying channel, subfamily J, member 11) on impaired hypoglycaemia awareness in 217 patients with T1D were studied.
705	16186394	To test this prediction, we crossed mice lacking neuroendocrine glucokinase (nGK(+/-)) with mice lacking K(ATP) channels (Kir6.2(-/-)).
706	16186394	In the presence of glutamine, isolated nGK(+/-)Kir6.2(-/-) islets show improved insulin secretion compared with nGK(+/-)Kir6.2(+/+).
707	16186394	To test this prediction, we crossed mice lacking neuroendocrine glucokinase (nGK(+/-)) with mice lacking K(ATP) channels (Kir6.2(-/-)).
708	16186394	In the presence of glutamine, isolated nGK(+/-)Kir6.2(-/-) islets show improved insulin secretion compared with nGK(+/-)Kir6.2(+/+).
709	16198094	The 2 subunits of the K(+)(ATP) channel are encoded by either the sulfonylurea receptor gene (SUR1 or ABCC8) or the inward-rectifying potassium channel gene (KIR6.2. or KCNJ11), both located in the 11p15.1 region.
710	16198094	Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion.
711	16198094	Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous.
712	16198094	The 2 subunits of the K(+)(ATP) channel are encoded by either the sulfonylurea receptor gene (SUR1 or ABCC8) or the inward-rectifying potassium channel gene (KIR6.2. or KCNJ11), both located in the 11p15.1 region.
713	16198094	Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion.
714	16198094	Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous.
715	16198094	The 2 subunits of the K(+)(ATP) channel are encoded by either the sulfonylurea receptor gene (SUR1 or ABCC8) or the inward-rectifying potassium channel gene (KIR6.2. or KCNJ11), both located in the 11p15.1 region.
716	16198094	Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion.
717	16198094	Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous.
718	16249427	The prediction that K ATP channel "overactivity" should cause a diabetic state due to undersecretion of insulin has been dramatically borne out by recent genetic studies implicating "activating" mutations in the Kir6.2 subunit of K ATP channel as causal in human diabetes.
719	16268330	Making a diagnosis of monogenic diabetes is important as it can have a dramatic effect on the treatment a patient should receive: glucokinase MODY patients need no treatment; HNF1alpha MODY patients are very sensitive to low dose sulphonylureas; and patients with neonatal diabetes due to Kir6.2 mutations, despite being insulin dependent, can discontinue insulin and be well controlled on high dose sulphonylurea tablets.
720	16306272	Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of the pancreatic ATP-sensitive K+ channel (K(ATP) channel), which is essential for triggering insulin secretion via membrane depolarization.
721	16306272	To investigate the role of SUR in apoptosis induction, we tested the effect of glibenclamide on recombinant human embryonic kidney 293 cells expressing either SUR1, the smooth muscular isoform SUR2B, or the mutant SUR1(M1289T) at which a single amino acid in transmembrane helix 17 (TM17) was exchanged by the corresponding amino acid of SUR2.
722	16306272	By analyzing cell detachment, nuclear condensation, DNA fragmentation, and caspase-3-like activity, we observed a SUR1-specific enhancement of glibenclamide-induced apoptosis that was not seen in SUR2B, SUR1(M1289T), or control cells.
723	16306272	This effect does not require the presence of functional Kir6.2-containing K(ATP) channels, which points to additional, so far unknown functions of SUR.
724	16332676	Loss of KATP channel function due to mutations in ABCC8 or KCNJ11, genes that encode the sulfonylurea receptor 1 or the inward rectifier Kir6.2 subunit of the channel, is a major cause of congenital hyperinsulinism.
725	16335696	[Two promising candidate genes in the ethiopathogenesis of DM2 - PPARgamma2 and KCNJ11].
726	16335696	The KCNJ11 gene codes for a pore-forming subunit of the inwardly rectifying ATP sensitive K+ channel, which is involved in the direct regulation of insulin secretion.
727	16335696	[Two promising candidate genes in the ethiopathogenesis of DM2 - PPARgamma2 and KCNJ11].
728	16335696	The KCNJ11 gene codes for a pore-forming subunit of the inwardly rectifying ATP sensitive K+ channel, which is involved in the direct regulation of insulin secretion.
729	16339180	The greater ATP inhibition of mutant Kir6.2/SUR2A than of Kir6.2/SUR1 can explain why gain-of-function Kir6.2 mutations manifest effects in brain and beta-cells but not in the heart.
730	16339272	Overexpression of Kruppel-like factor 7 regulates adipocytokine gene expressions in human adipocytes and inhibits glucose-induced insulin secretion in pancreatic beta-cell line.
731	16339272	We have identified Kruppel-like factor 7 (KLF7) as a new candidate for conferring susceptibility to type 2 diabetes.
732	16339272	In human adipocytes overexpressing KLF7, the expression of adiponectin and leptin was decreased compared with that in control cells, whereas expression of IL-6 was increased.
733	16339272	In the insulin-secreting cell line (HIT-T15 cells), the expression and glucose-induced secretion of insulin were significantly suppressed in KLF7-overexpressed cells compared with control cells, accompanied by the reduction in the expression of glucose transporter 2, sulfonylurea receptor 1, Kir6.2, and pancreatic-duodenal homeobox factor 1.
734	16339272	We also found that the overexpression of KLF7 resulted in the decrease of hexokinase 2 expression in smooth muscle cells, and of glucose transporter 2 expression in the HepG2 cells.
735	16339272	These results suggest that KLF7 may contribute to the pathogenesis of type 2 diabetes through an impairment of insulin biosynthesis and secretion in pancreatic beta-cells and a reduction of insulin sensitivity in peripheral tissues.
736	16367885	IRS1, KCNJ11, PPARgamma2 and HNF-1alpha: do amino acid polymorphisms in these candidate genes support a shared aetiology between type 1 and type 2 diabetes?
737	16375017	Patients with neonatal DM are normally dependent on life-long insulin injections, but patients with neonatal DM due to a KCNJ11 mutation are able to achieve control with sulphonylurea tablets.
738	16377800	Mutations in the hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of glucose-stimulated insulin secretion by pancreatic beta-cells.
739	16377800	The betaHNF-4alphaKO mice exhibited impairment of glucose-stimulated insulin secretion, which is a characteristic of MODY1.
740	16377800	Pancreatic islet morphology, beta-cell mass, and insulin content were normal in the HNF-4alpha mutant mice.
741	16377800	Expression levels of Kir6.2 and SUR1 proteins in the betaHNF-4alphaKO mice were unchanged as compared with control mice.
742	16380471	The focal condition is caused by a paternally inherited mutation in one of the genes encoding the subunits of the beta-cell ATP-sensitive potassium channel (SUR1/ABCC8 or Kir6.2/KCNJ11) and somatic loss of maternal 11p15 alleles within the affected area.
743	16416420	Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism.
744	16416420	The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1.
745	16416420	It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinemia (HI) of infancy; however, heterozygous activating mutations in KCNJ11 that result in the opposite phenotype of diabetes have recently been described.
746	16416420	Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism.
747	16416420	The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1.
748	16416420	It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinemia (HI) of infancy; however, heterozygous activating mutations in KCNJ11 that result in the opposite phenotype of diabetes have recently been described.
749	16416420	Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism.
750	16416420	The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1.
751	16416420	It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinemia (HI) of infancy; however, heterozygous activating mutations in KCNJ11 that result in the opposite phenotype of diabetes have recently been described.
752	16429105	A number of conditions are associated with PNDM, some of which have been elucidated at the molecular levels Among those, the very recently elucidated mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic KATP channel involved in regulation of insulin secretion accounts for one third to a half of the PNDM cases.
753	16475928	Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives.
754	16475928	In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin.
755	16475928	The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues.
756	16475928	Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes.
757	16475928	Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI).
758	16475928	Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS.
759	16475928	The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued.
760	16475928	NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies.
761	16475928	Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives.
762	16475928	In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin.
763	16475928	The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues.
764	16475928	Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes.
765	16475928	Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI).
766	16475928	Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS.
767	16475928	The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued.
768	16475928	NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies.
769	16475928	Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives.
770	16475928	In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin.
771	16475928	The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues.
772	16475928	Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes.
773	16475928	Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI).
774	16475928	Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS.
775	16475928	The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued.
776	16475928	NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies.
777	16475928	Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives.
778	16475928	In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin.
779	16475928	The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues.
780	16475928	Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes.
781	16475928	Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI).
782	16475928	Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS.
783	16475928	The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued.
784	16475928	NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies.
785	16475928	Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives.
786	16475928	In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin.
787	16475928	The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues.
788	16475928	Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes.
789	16475928	Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI).
790	16475928	Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS.
791	16475928	The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued.
792	16475928	NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies.
793	16475928	Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives.
794	16475928	In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin.
795	16475928	The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues.
796	16475928	Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes.
797	16475928	Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI).
798	16475928	Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS.
799	16475928	The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued.
800	16475928	NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies.
801	16475928	Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives.
802	16475928	In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin.
803	16475928	The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues.
804	16475928	Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes.
805	16475928	Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI).
806	16475928	Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS.
807	16475928	The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued.
808	16475928	NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies.
809	16475928	Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives.
810	16475928	In pancreatic beta cells the K(ATP) channels, which are formed by 4 ion channels (Kir6.2) and 4 regulatory sulfonylurea receptors (SUR1), control the glucose stimulated release of insulin.
811	16475928	The Kir6.2/SUR1 K(ATP) channels are also present in the brain and in other neuroendocrine tissues.
812	16475928	Blockers of Kir6.2/SUR1 channels, e.g. glibenclamide and repaglinide stimulate release of insulin and are used for treatment of type 2 diabetes.
813	16475928	Openers of Kir6.2/SUR1 channels, e.g. diazoxide, have in contrast only found limited clinical use in treatment of hypersecretion of insulin associated with certain tumours (insulinoma) and genetic disorders (persistent hyperinsulinemia and hypoglycemia of infancy, PHHI).
814	16475928	Recent studies have however, indicated that openers of Kir6.2/SUR1 channels could be useful in treatment of e.g. metabolic disorders and diseases of the CNS.
815	16475928	The clinical use of diazoxide has been hampered by its lack of potency and selectivity giving rise to side effects, such as oedema and hirsutism and new selective openers of Kir6.2/SUR1 channels have been pursued.
816	16475928	NN414 has been shown to be a potent and Kir6.2/SUR1 selective K(ATP) channels opener, which inhibits glucose stimulated insulin release in vitro and in vivo and which has beneficial effects on glucose homeostasis in preclinical and clinical studies.
817	16595597	The E23K variant of KCNJ11 encoding the pancreatic beta-cell adenosine 5'-triphosphate-sensitive potassium channel subunit Kir6.2 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes.
818	16613899	Residue F132 shows evolutionary conservation across species and is located in the first set of transmembrane helices (TMD0) of SUR1, which is proposed to interact with Kir6.2.
819	16613899	The functional consequence of this ABCC8 mutation mirrors that of KCNJ11 mutations causing neonatal diabetes and provides new insights into the interaction of Kir6.2 and SUR1.
820	16613899	Residue F132 shows evolutionary conservation across species and is located in the first set of transmembrane helices (TMD0) of SUR1, which is proposed to interact with Kir6.2.
821	16613899	The functional consequence of this ABCC8 mutation mirrors that of KCNJ11 mutations causing neonatal diabetes and provides new insights into the interaction of Kir6.2 and SUR1.
822	16731833	Wild-type or mutant Kir6.2/SUR1 channels were examined by heterologous expression in Xenopus oocytes.
823	16772326	Genes underrepresented in ZDF islets were either unaffected (Glut-2, Kir6.2, Rab3), stimulated (voltage-dependent Ca(2+) channel subunit alpha1D, CPT2, SUR2, rab9, syt13), or inhibited (syntaxin 7, secretogranin-2) by SREBP-1c inhibition.
824	16772326	Correspondingly, SREBP-1c DN largely corrected decreases in the expression of the transcription factors Pdx-1 and MafA but did not affect the abnormalities in Pax6, Arx, hepatic nuclear factor-1alpha (HNF1alpha), HNF3beta/Forkhead box-a2 (Foxa2), inducible cyclic AMP early repressor (ICER), or transcription factor 7-like 2 (TCF7L2) expression observed in ZDF islets.
825	16816952	Sulfonylurea treatment outweighs insulin therapy in short-term metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 (KIR6.2) gene.
826	16821773	Compound 1a (NN414) is a potent opener of Kir6.2/SUR1 K(ATP) channels.
827	16821773	Several compounds, e.g., 6-chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1h), were found to be potent openers of Kir6.2/SUR1 K(ATP) channels and were able to suppress glucose-stimulated insulin release from rat islets in vitro (EC(50) = 0.04 +/- 0.01 muM) and in vivo after intravenous or peroral administration to hyperinsulinemic obese Zucker rats (ED(50) = 4.0 mg/kg).
828	16821773	Compound 1a (NN414) is a potent opener of Kir6.2/SUR1 K(ATP) channels.
829	16821773	Several compounds, e.g., 6-chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1h), were found to be potent openers of Kir6.2/SUR1 K(ATP) channels and were able to suppress glucose-stimulated insulin release from rat islets in vitro (EC(50) = 0.04 +/- 0.01 muM) and in vivo after intravenous or peroral administration to hyperinsulinemic obese Zucker rats (ED(50) = 4.0 mg/kg).
830	16873704	We examined the association of variants in genes encoding several transcription factors (TCF1, TCF2, HNF4A, ISL1, IPF1, NEUROG3, PAX6, NKX2-2, NKX6-1, and NEUROD1) and genes encoding the ATP-sensitive K(+) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) with type 2 diabetes in a Japanese cohort of 2,834 subjects.
831	16885550	Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations.
832	16897043	ABCC8 and ABCC9: ABC transporters that regulate K+ channels.
833	16897043	The sulfonylurea receptors (SURs) ABCC8/SUR1 and ABCC9/SUR2 are members of the C-branch of the transport adenosine triphosphatase superfamily.
834	16897043	Unlike their brethren, the SURs have no identified transport function; instead, evolution has matched these molecules with K(+) selective pores, either K(IR)6.1/KCNJ8 or K(IR)6.2/KCNJ11, to assemble adenosine triphosphate (ATP)-sensitive K(+) channels found in endocrine cells, neurons, and both smooth and striated muscle.
835	16897043	Mutations in either subunit can alter this balance and, in the case of the SUR1/KIR6.2 channels found in neurons and insulin-secreting pancreatic beta cells, are the cause of monogenic forms of hyperinsulinemic hypoglycemia and neonatal diabetes.
836	16897043	ABCC8 and ABCC9: ABC transporters that regulate K+ channels.
837	16897043	The sulfonylurea receptors (SURs) ABCC8/SUR1 and ABCC9/SUR2 are members of the C-branch of the transport adenosine triphosphatase superfamily.
838	16897043	Unlike their brethren, the SURs have no identified transport function; instead, evolution has matched these molecules with K(+) selective pores, either K(IR)6.1/KCNJ8 or K(IR)6.2/KCNJ11, to assemble adenosine triphosphate (ATP)-sensitive K(+) channels found in endocrine cells, neurons, and both smooth and striated muscle.
839	16897043	Mutations in either subunit can alter this balance and, in the case of the SUR1/KIR6.2 channels found in neurons and insulin-secreting pancreatic beta cells, are the cause of monogenic forms of hyperinsulinemic hypoglycemia and neonatal diabetes.
840	16956886	Reduced K(ATP) channel expression caused by mutations in the channel proteins: sulfonylurea receptor 1 (SUR1) and Kir6.2, results in loss of channel function as seen in congenital hyperinsulinism.
841	16956886	Interestingly, rescue of the trafficking defects requires mutant SUR1 to be co-expressed with Kir6.2, suggesting that the channel complex, rather than SUR1 alone, is the drug target.
842	16956886	Observations that sulfonylureas also reverse trafficking defects caused by neonatal diabetes-associated Kir6.2 mutations in a way that is dependent on intact sulfonylurea binding sites in SUR1 further support this notion.
843	16956886	Reduced K(ATP) channel expression caused by mutations in the channel proteins: sulfonylurea receptor 1 (SUR1) and Kir6.2, results in loss of channel function as seen in congenital hyperinsulinism.
844	16956886	Interestingly, rescue of the trafficking defects requires mutant SUR1 to be co-expressed with Kir6.2, suggesting that the channel complex, rather than SUR1 alone, is the drug target.
845	16956886	Observations that sulfonylureas also reverse trafficking defects caused by neonatal diabetes-associated Kir6.2 mutations in a way that is dependent on intact sulfonylurea binding sites in SUR1 further support this notion.
846	16956886	Reduced K(ATP) channel expression caused by mutations in the channel proteins: sulfonylurea receptor 1 (SUR1) and Kir6.2, results in loss of channel function as seen in congenital hyperinsulinism.
847	16956886	Interestingly, rescue of the trafficking defects requires mutant SUR1 to be co-expressed with Kir6.2, suggesting that the channel complex, rather than SUR1 alone, is the drug target.
848	16956886	Observations that sulfonylureas also reverse trafficking defects caused by neonatal diabetes-associated Kir6.2 mutations in a way that is dependent on intact sulfonylurea binding sites in SUR1 further support this notion.
849	17021801	ATP-sensitive potassium (K(ATP)) channels, composed of pore-forming Kir6.2 and regulatory sulphonylurea receptor (SUR) subunits, play an essential role in insulin secretion from pancreatic beta cells.
850	17021801	Binding of ATP to Kir6.2 inhibits, whereas interaction of Mg-nucleotides with SUR, activates the channel.
851	17021801	K(ATP) channels were expressed in Xenopus oocytes and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of SUR).
852	17021801	ATP-sensitive potassium (K(ATP)) channels, composed of pore-forming Kir6.2 and regulatory sulphonylurea receptor (SUR) subunits, play an essential role in insulin secretion from pancreatic beta cells.
853	17021801	Binding of ATP to Kir6.2 inhibits, whereas interaction of Mg-nucleotides with SUR, activates the channel.
854	17021801	K(ATP) channels were expressed in Xenopus oocytes and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of SUR).
855	17021801	ATP-sensitive potassium (K(ATP)) channels, composed of pore-forming Kir6.2 and regulatory sulphonylurea receptor (SUR) subunits, play an essential role in insulin secretion from pancreatic beta cells.
856	17021801	Binding of ATP to Kir6.2 inhibits, whereas interaction of Mg-nucleotides with SUR, activates the channel.
857	17021801	K(ATP) channels were expressed in Xenopus oocytes and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of SUR).
858	17065345	A Kir6.2 mutation causing neonatal diabetes impairs electrical activity and insulin secretion from INS-1 beta-cells.
859	17065345	Transfection with wild-type Kir6.2 had no effect on the ATP sensitivity of the K(ATP) channel, whole-cell K(ATP) current magnitude, or insulin secretion.
860	17065345	Thus, these results directly demonstrate that Kir6.2 mutations prevent electrical activity and insulin release from INS-1 cells by increasing the K(ATP) current and hyperpolarizing the beta-cell membrane.
861	17065345	A Kir6.2 mutation causing neonatal diabetes impairs electrical activity and insulin secretion from INS-1 beta-cells.
862	17065345	Transfection with wild-type Kir6.2 had no effect on the ATP sensitivity of the K(ATP) channel, whole-cell K(ATP) current magnitude, or insulin secretion.
863	17065345	Thus, these results directly demonstrate that Kir6.2 mutations prevent electrical activity and insulin release from INS-1 cells by increasing the K(ATP) current and hyperpolarizing the beta-cell membrane.
864	17065345	A Kir6.2 mutation causing neonatal diabetes impairs electrical activity and insulin secretion from INS-1 beta-cells.
865	17065345	Transfection with wild-type Kir6.2 had no effect on the ATP sensitivity of the K(ATP) channel, whole-cell K(ATP) current magnitude, or insulin secretion.
866	17065345	Thus, these results directly demonstrate that Kir6.2 mutations prevent electrical activity and insulin release from INS-1 cells by increasing the K(ATP) current and hyperpolarizing the beta-cell membrane.
867	17137217	Analyses of covariance adjusting for age, body mass index, hyperlipidemia, diabetes, smoking, drinking, and antihypertensive medication revealed that 17 polymorphisms in 16 genes (APOB, CAST, CLCNKB, CTNS, GHR, GYS1, HF1, IKBKAP, KCNJ11, LIPC, LPL, P2RY2, PON2, SLC4A1, TRH, VWF) were significantly associated with blood pressure variations.
868	17137217	Multivariate logistic regression analysis with adjustment for the same factors revealed that 11 polymorphisms in 11 genes (CAST, CTLA4, F5, GC, GHR, LIPC, PLA2G7, SLC4A1, SLCI8A1, TRH, VWF) showed significant associations with hypertension.
869	17137217	Five polymorphisms in five genes, CAST(calpastatin), LIPC (hepatic lipase), SLC4A1 (band 3 anion transporter), TRH (thyrotropin-releasing hormone), and VWF (von Willebrand factor), were significantly associated with both blood pressure variation and hypertension.
870	17186387	It has resulted in great challenges for researchers elucidating the aetiology of diabetes and related features in other organ systems, for clinicians specifying a diagnosis that leads to improved genetic counselling, predicting of clinical course and changes in treatment, and for patients to altered treatment that has lead to coming off insulin and injections with no alternative (Glucokinase mutations), insulin injections being replaced by tablets (e.g. low dose in HNFalpha or high dose in potassium channel defects -Kir6.2 and SUR1) or with tablets in addition to insulin (e.g. metformin in insulin resistant syndromes).
871	17192350	Transfer to sulphonylurea therapy in adult subjects with permanent neonatal diabetes due to KCNJ11-activating [corrected] mutations: evidence for improvement in insulin sensitivity.
872	17192490	In the combined data, we replicated association (P < 0.05) for 12 SNPs: PPARG Pro12Ala and His447, KCNJ11 Glu23Lys and rs5210, TNF -857, SLC2A2 Ile110Thr, HNF1A/TCF1 rs2701175 and GE117881_360, PCK1 -232, NEUROD1 Thr45Ala, IL6 -598, and ENPP1 Lys121Gln.
873	17213273	Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers.
874	17259403	As previously shown in other studies, lysine carriers at KCNJ11 E23K had reduced insulin secretion at baseline; however, they were less likely to develop diabetes than E/E homozygotes.
875	17259403	We conclude that the lysine variant in KCNJ11 E23K leads to diminished insulin secretion in individuals with IGT.
876	17259403	As previously shown in other studies, lysine carriers at KCNJ11 E23K had reduced insulin secretion at baseline; however, they were less likely to develop diabetes than E/E homozygotes.
877	17259403	We conclude that the lysine variant in KCNJ11 E23K leads to diminished insulin secretion in individuals with IGT.
878	17296510	These channels are octameric complex with two kind of subunits: four regulatory sulfonylurea receptor (SUR) embracing four poreforming inwardly rectifying potassium channel (Kir).
879	17296510	Several isoforms exist for each type of subunits: SUR1 is found in the pancreatic beta-cell and neurons, whereas SUR2A is in heart cells and SUR2B in smooth muscle; Kir6.2 is in the majority of tissues as pancreatic beta-cells, brain, heart and skeletal muscle, and Kir6.1 can be found in smooth vascular muscle and astrocytes.
880	17296510	Sulfonylureas close K(ATP) channels by binding with high affinity to SUR suggesting they could replace insulin in these patients.
881	17296510	Subsequently, more than 50 patients have been reported as successfully and safely switched from subcutaneous insulin injections to oral sulfonylurea therapy, with an improvement in their glycated hemoglobin.
882	17296510	We therefore designed a protocol to transfer and evaluate children who have insulin treated neonatal diabetes due to KCNJ11 mutation, from insulin to sulfonylurea.
883	17296510	These channels are octameric complex with two kind of subunits: four regulatory sulfonylurea receptor (SUR) embracing four poreforming inwardly rectifying potassium channel (Kir).
884	17296510	Several isoforms exist for each type of subunits: SUR1 is found in the pancreatic beta-cell and neurons, whereas SUR2A is in heart cells and SUR2B in smooth muscle; Kir6.2 is in the majority of tissues as pancreatic beta-cells, brain, heart and skeletal muscle, and Kir6.1 can be found in smooth vascular muscle and astrocytes.
885	17296510	Sulfonylureas close K(ATP) channels by binding with high affinity to SUR suggesting they could replace insulin in these patients.
886	17296510	Subsequently, more than 50 patients have been reported as successfully and safely switched from subcutaneous insulin injections to oral sulfonylurea therapy, with an improvement in their glycated hemoglobin.
887	17296510	We therefore designed a protocol to transfer and evaluate children who have insulin treated neonatal diabetes due to KCNJ11 mutation, from insulin to sulfonylurea.
888	17327429	PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells.
889	17327429	Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant.
890	17327429	Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets.
891	17327429	Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines.
892	17327429	Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells.
893	17327429	Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion.
894	17327429	In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells.
895	17327429	PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells.
896	17327429	Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant.
897	17327429	Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets.
898	17327429	Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines.
899	17327429	Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells.
900	17327429	Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion.
901	17327429	In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells.
902	17327429	PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells.
903	17327429	Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant.
904	17327429	Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets.
905	17327429	Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines.
906	17327429	Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells.
907	17327429	Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion.
908	17327429	In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells.
909	17331067	Some genes that have become accepted as contributors to diabetes risk include: calpain 10, peroxisome proliferator-activated receptor-gamma, ATP-sensitive inwardly rectifying potassium channel subunit Kir6.2, hepatocyte nuclear factor 4alpha and hepatic transcription factor 1.
910	17331067	In particular, we highlight recent reports of associations between Type 2 diabetes and the transcription factor 7-like 2 gene, associations with micro-opioid receptor and supressor of cytokine signaling 2 genes, and expression and functional analyses of adipokines vaspin and retinol binding protein 4.
911	17346148	In addition, common variants in several candidate genes (e.g. potassium inwardly rectifying channel subfamily J, member 11 [KCNJ11], Glucokinase [GCK], Hepatocyte nuclear factor-1alpha [HNF1A] etc.) have been demonstrated to increase the risk of GDM.
912	17349054	Among these, the very recently elucidated mutations in the KCNJ11 and ABCC8 genes, encoding the Kir6.2 and SUR1 subunit of the pancreatic KATP channel involved in regulation of insulin secretion, account for one third to half of the PNDM cases.
913	17349054	Molecular analysis of chromosome 6 anomalies (found in more than 60% in TNDM), and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1, provides a tool to identify TNDM from PNDM in the neonatal period.
914	17349054	This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 genes, from insulin therapy to sulfonylureas.
915	17349054	Among these, the very recently elucidated mutations in the KCNJ11 and ABCC8 genes, encoding the Kir6.2 and SUR1 subunit of the pancreatic KATP channel involved in regulation of insulin secretion, account for one third to half of the PNDM cases.
916	17349054	Molecular analysis of chromosome 6 anomalies (found in more than 60% in TNDM), and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1, provides a tool to identify TNDM from PNDM in the neonatal period.
917	17349054	This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 genes, from insulin therapy to sulfonylureas.
918	17349054	Among these, the very recently elucidated mutations in the KCNJ11 and ABCC8 genes, encoding the Kir6.2 and SUR1 subunit of the pancreatic KATP channel involved in regulation of insulin secretion, account for one third to half of the PNDM cases.
919	17349054	Molecular analysis of chromosome 6 anomalies (found in more than 60% in TNDM), and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1, provides a tool to identify TNDM from PNDM in the neonatal period.
920	17349054	This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 genes, from insulin therapy to sulfonylureas.
921	17378627	Pancreatectomy may be required in severe cases, most of which result from a defect in the beta-cell KATP channel, encoded by ABCC8 and KCNJ11.
922	17378627	ABCC8 and KCNJ11 genes were sequenced and case histology was reviewed in 21 infants who had pancreatectomy.
923	17378627	Pancreatectomy may be required in severe cases, most of which result from a defect in the beta-cell KATP channel, encoded by ABCC8 and KCNJ11.
924	17378627	ABCC8 and KCNJ11 genes were sequenced and case histology was reviewed in 21 infants who had pancreatectomy.
925	17389331	Recently, we have described the novel mechanism where basal Mg-nucleotide-dependent stimulatory action of SUR1 on the Kir6.2 pore is increased.
926	17389331	In our present study, we identified six new heterozygous ABCC8 mutations, mainly in patients presenting the transient form of neonatal diabetes (six of eight), with a median duration of initial insulin therapy of 17 months (range 0.5-38.0).
927	17389331	Whereas Kir6.2 mutations are a common cause of permanent neonatal diabetes and in a few cases associate with the DEND (developmental delay, epilepsy, and neonatal diabetes) syndrome, SUR1 mutations are more frequent in transient (52%) compared with permanent (14%) neonatal diabetes cases screened for ABCC8 in our series.
928	17389331	Recently, we have described the novel mechanism where basal Mg-nucleotide-dependent stimulatory action of SUR1 on the Kir6.2 pore is increased.
929	17389331	In our present study, we identified six new heterozygous ABCC8 mutations, mainly in patients presenting the transient form of neonatal diabetes (six of eight), with a median duration of initial insulin therapy of 17 months (range 0.5-38.0).
930	17389331	Whereas Kir6.2 mutations are a common cause of permanent neonatal diabetes and in a few cases associate with the DEND (developmental delay, epilepsy, and neonatal diabetes) syndrome, SUR1 mutations are more frequent in transient (52%) compared with permanent (14%) neonatal diabetes cases screened for ABCC8 in our series.
931	17395632	The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits.
932	17395632	The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation.
933	17395632	In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels.
934	17395632	These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2.
935	17395632	This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation.
936	17395632	The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2.
937	17395632	Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2.
938	17395632	The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits.
939	17395632	The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation.
940	17395632	In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels.
941	17395632	These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2.
942	17395632	This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation.
943	17395632	The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2.
944	17395632	Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2.
945	17395632	The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits.
946	17395632	The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation.
947	17395632	In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels.
948	17395632	These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2.
949	17395632	This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation.
950	17395632	The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2.
951	17395632	Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2.
952	17395632	The Kir6.2-F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits.
953	17395632	The open probability of Kir6.2/SUR1 channels, or a C-terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation.
954	17395632	In the absence of Mg2+, ATP inhibition of all Kir6.2-F333I/SUR channel types was reduced, although SUR1-containing channels were reduced more than SUR2-containing channels.
955	17395632	These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2.
956	17395632	This indicates Mg-nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation.
957	17395632	The data further suggest that MgATP hydrolysis by the nucleotide-binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2.
958	17395632	Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2.
959	17409272	Although both compounds do not have a sulfonylurea structure, it has been postulated that insulin secretion is preceded by their binding to Kir6.2/SUR1 complex, and a mechanism of insulin secretion of glinides has been accounted for by this pathway.
960	17431820	One of them is the cardiac ATP-sensitive potassium channel (K(ATP)), which is an octamer composed of four pore-forming inwardly rectifying potassium-channel subunits (Kir6.2) and four regulatory sulfonylurea-receptor subunits (SUR2A).
961	17446535	In patients in whom no abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the Kir6.2 and SUR1 subunits of the pancreatic beta-cell K(ATP) channel, were sequenced.
962	17446535	K(ATP) channel mutations were found in 25 of 97 (26%) TNDM probands (12 KCNJ11 and 13 ABCC8), while 69 of 97 (71%) had chromosome 6q24 abnormalities.
963	17446535	The phenotype associated with KCNJ11 and ABCC8 mutations was similar but markedly different from 6q24 patients who had a lower birth weight and who were diagnosed and remitted earlier (all P < 0.001).
964	17446535	In patients in whom no abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the Kir6.2 and SUR1 subunits of the pancreatic beta-cell K(ATP) channel, were sequenced.
965	17446535	K(ATP) channel mutations were found in 25 of 97 (26%) TNDM probands (12 KCNJ11 and 13 ABCC8), while 69 of 97 (71%) had chromosome 6q24 abnormalities.
966	17446535	The phenotype associated with KCNJ11 and ABCC8 mutations was similar but markedly different from 6q24 patients who had a lower birth weight and who were diagnosed and remitted earlier (all P < 0.001).
967	17446535	In patients in whom no abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the Kir6.2 and SUR1 subunits of the pancreatic beta-cell K(ATP) channel, were sequenced.
968	17446535	K(ATP) channel mutations were found in 25 of 97 (26%) TNDM probands (12 KCNJ11 and 13 ABCC8), while 69 of 97 (71%) had chromosome 6q24 abnormalities.
969	17446535	The phenotype associated with KCNJ11 and ABCC8 mutations was similar but markedly different from 6q24 patients who had a lower birth weight and who were diagnosed and remitted earlier (all P < 0.001).
970	17463248	We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk.
971	17491708	Assessment of insulin sensitivity in adults with permanent neonatal diabetes mellitus due to mutations in the KCNJ11 gene encoding Kir6.2.
972	17491708	The main pathophysiological feature of PNDM associated with Kir6.2 mutations is a profound defect in insulin secretion.
973	17491708	Thus, the hypothesis that Kir6.2 mutations may influence insulin sensitivity in humans seems justified.
974	17491708	Four adult carriers of a Kir6.2 mutation from the Polish population (mean age 31.5 years, range 20-50) were available for this study that aimed to evaluate their insulin sensitivity by the hyperinsulinemic euglycemic clamp technique.
975	17491708	This observation suggests that impaired insulin sensitivity, in addition to profoundly decreased insulin secretion, contributes to the clinical picture of PNDM resulting from mutations in the Kir6.2 gene.
976	17491708	The intriguing question to be answered in the future is whether an improvement in insulin action could be seen following the transfer of Kir6.2 mutation carriers to sulphonylurea compounds.
977	17491708	Assessment of insulin sensitivity in adults with permanent neonatal diabetes mellitus due to mutations in the KCNJ11 gene encoding Kir6.2.
978	17491708	The main pathophysiological feature of PNDM associated with Kir6.2 mutations is a profound defect in insulin secretion.
979	17491708	Thus, the hypothesis that Kir6.2 mutations may influence insulin sensitivity in humans seems justified.
980	17491708	Four adult carriers of a Kir6.2 mutation from the Polish population (mean age 31.5 years, range 20-50) were available for this study that aimed to evaluate their insulin sensitivity by the hyperinsulinemic euglycemic clamp technique.
981	17491708	This observation suggests that impaired insulin sensitivity, in addition to profoundly decreased insulin secretion, contributes to the clinical picture of PNDM resulting from mutations in the Kir6.2 gene.
982	17491708	The intriguing question to be answered in the future is whether an improvement in insulin action could be seen following the transfer of Kir6.2 mutation carriers to sulphonylurea compounds.
983	17491708	Assessment of insulin sensitivity in adults with permanent neonatal diabetes mellitus due to mutations in the KCNJ11 gene encoding Kir6.2.
984	17491708	The main pathophysiological feature of PNDM associated with Kir6.2 mutations is a profound defect in insulin secretion.
985	17491708	Thus, the hypothesis that Kir6.2 mutations may influence insulin sensitivity in humans seems justified.
986	17491708	Four adult carriers of a Kir6.2 mutation from the Polish population (mean age 31.5 years, range 20-50) were available for this study that aimed to evaluate their insulin sensitivity by the hyperinsulinemic euglycemic clamp technique.
987	17491708	This observation suggests that impaired insulin sensitivity, in addition to profoundly decreased insulin secretion, contributes to the clinical picture of PNDM resulting from mutations in the Kir6.2 gene.
988	17491708	The intriguing question to be answered in the future is whether an improvement in insulin action could be seen following the transfer of Kir6.2 mutation carriers to sulphonylurea compounds.
989	17491708	Assessment of insulin sensitivity in adults with permanent neonatal diabetes mellitus due to mutations in the KCNJ11 gene encoding Kir6.2.
990	17491708	The main pathophysiological feature of PNDM associated with Kir6.2 mutations is a profound defect in insulin secretion.
991	17491708	Thus, the hypothesis that Kir6.2 mutations may influence insulin sensitivity in humans seems justified.
992	17491708	Four adult carriers of a Kir6.2 mutation from the Polish population (mean age 31.5 years, range 20-50) were available for this study that aimed to evaluate their insulin sensitivity by the hyperinsulinemic euglycemic clamp technique.
993	17491708	This observation suggests that impaired insulin sensitivity, in addition to profoundly decreased insulin secretion, contributes to the clinical picture of PNDM resulting from mutations in the Kir6.2 gene.
994	17491708	The intriguing question to be answered in the future is whether an improvement in insulin action could be seen following the transfer of Kir6.2 mutation carriers to sulphonylurea compounds.
995	17491708	Assessment of insulin sensitivity in adults with permanent neonatal diabetes mellitus due to mutations in the KCNJ11 gene encoding Kir6.2.
996	17491708	The main pathophysiological feature of PNDM associated with Kir6.2 mutations is a profound defect in insulin secretion.
997	17491708	Thus, the hypothesis that Kir6.2 mutations may influence insulin sensitivity in humans seems justified.
998	17491708	Four adult carriers of a Kir6.2 mutation from the Polish population (mean age 31.5 years, range 20-50) were available for this study that aimed to evaluate their insulin sensitivity by the hyperinsulinemic euglycemic clamp technique.
999	17491708	This observation suggests that impaired insulin sensitivity, in addition to profoundly decreased insulin secretion, contributes to the clinical picture of PNDM resulting from mutations in the Kir6.2 gene.
1000	17491708	The intriguing question to be answered in the future is whether an improvement in insulin action could be seen following the transfer of Kir6.2 mutation carriers to sulphonylurea compounds.
1001	17491708	Assessment of insulin sensitivity in adults with permanent neonatal diabetes mellitus due to mutations in the KCNJ11 gene encoding Kir6.2.
1002	17491708	The main pathophysiological feature of PNDM associated with Kir6.2 mutations is a profound defect in insulin secretion.
1003	17491708	Thus, the hypothesis that Kir6.2 mutations may influence insulin sensitivity in humans seems justified.
1004	17491708	Four adult carriers of a Kir6.2 mutation from the Polish population (mean age 31.5 years, range 20-50) were available for this study that aimed to evaluate their insulin sensitivity by the hyperinsulinemic euglycemic clamp technique.
1005	17491708	This observation suggests that impaired insulin sensitivity, in addition to profoundly decreased insulin secretion, contributes to the clinical picture of PNDM resulting from mutations in the Kir6.2 gene.
1006	17491708	The intriguing question to be answered in the future is whether an improvement in insulin action could be seen following the transfer of Kir6.2 mutation carriers to sulphonylurea compounds.
1007	17496234	The actions of a novel potent islet beta-cell specific ATP-sensitive K+ channel opener can be modulated by syntaxin-1A acting on sulfonylurea receptor 1.
1008	17496234	We reported that syntaxin-1A binds nucleotide binding folds of sulfonylurea receptor 1 (SUR1) in beta-cells to inhibit K(ATP) channels.
1009	17496234	Whole-cell and inside-out patch-clamp electrophysiology was used to examine the effects of glutathione S-transferase (GST)-syntaxin-1A dialysis or green fluorescence protein/syntaxin-1A cotransfection on NNC55-0462 actions.
1010	17496234	Dialysis of GST-syntaxin-1A into the cell cytoplasm reduced both potency and efficacy of extracellularly perfused NNC55-0462 in a HEK cell line stably expressing Kir6.2/SUR1 (BA8 cells) and in rat islet beta-cells.
1011	17496234	Moreover, inside-out membrane patches excised from BA8 cells showed that both GST-syntaxin-1A and its H3 domain inhibited K(ATP) channels previously activated by NNC55-0462.
1012	17496234	This action on K(ATP) channels is isoform-specific to syntaxin-1A because syntaxin-2 was without effect.
1013	17496234	Furthermore, the parent compound diazoxide showed similar sensitivity to GST-syntaxin-1A inhibition.
1014	17522344	Finally, iptakalim inhibited Kir6.2/SUR1, but it activated Kir6.1/SUR2B (vascular-type), K(ATP) channels heterologously expressed in Xenopus oocytes.
1015	17535866	Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes.
1016	17561964	Despite a huge amount of effort, progress was disappointing and only two genes, PPARG and KCNJ11, were confirmed beyond doubt as Type 2 diabetes risk factors in multiple studies.
1017	17575084	Mutations in the pancreatic ATP-sensitive K(+) (K(ATP)) channel proteins sulfonylurea receptor 1 (SUR1) and Kir6.2, encoded by ABCC8 and KCNJ11, respectively, is the most common cause of the disease.
1018	17584766	Activating mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 and SUR1 are a common cause of neonatal diabetes.
1019	17584766	They also provide further evidence that interactions between TMD0 of SUR1 and Kir6.2 are critical for K(ATP) channel gating and identify a residue crucial for this interaction at both physical and functional levels.
1020	17584766	Activating mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 and SUR1 are a common cause of neonatal diabetes.
1021	17584766	They also provide further evidence that interactions between TMD0 of SUR1 and Kir6.2 are critical for K(ATP) channel gating and identify a residue crucial for this interaction at both physical and functional levels.
1022	17652156	The beta-cell K(ATP) channel comprises pore-forming Kir6.2 and regulatory SUR1 subunits, and mutations in either type of subunit can result in too little or too much insulin release.
1023	17659066	Transition from insulin to glyburide in a 4-month-old girl with neonatal diabetes mellitus caused by a mutation in KCNJ11.
1024	17659066	We report on the transition from insulin to glyburide (glibenclamide) therapy in a 4-month-old girl with neonatal diabetes mellitus caused by a mutation in KCNJ11.
1025	17659066	Transition from insulin to glyburide in a 4-month-old girl with neonatal diabetes mellitus caused by a mutation in KCNJ11.
1026	17659066	We report on the transition from insulin to glyburide (glibenclamide) therapy in a 4-month-old girl with neonatal diabetes mellitus caused by a mutation in KCNJ11.
1027	17666135	KATP channels are made up of four subunits each of Kir6.2 and the sulphonylurea receptor (SUR1), encoded by the genes KCNJ11 and ABCC8, respectively.
1028	17701889	The effects of NN414, a SUR1/Kir6.2 selective potassium channel opener in subjects with type 2 diabetes.
1029	17709898	MIN6 cells co-cultured with 3T3-L1 adipocytes had significantly reduced intracellular calcium concentration ([Ca2+]i) and lost the ability to secrete insulin in response to tolbutamide, compared to the control cells. 3T3-L1 adipocytes significantly decreased the expression of insulin, glucokinase and Kir6.2 genes but increased the expression of uncoupling protein-2 (UCP-2) in MIN6 cells after one week of co-culture, as measured by semi-quantitative RT-PCR. 3T3-L1 adipocyte-conditioned medium also significantly decreased insulin secretion and the expression of insulin, glucokinase and Kir6.2 genes in MIN6 cells.
1030	17709898	The inhibitor of protein tyrosine kinase, genistein, decreased the expression of glucokinase and Kir6.2 in MIN6 cells, while two free fatty acids, oleic acid and linoleic acids, were found to increase UCP-2 expression.
1031	17709898	The effects of T3-L1 adipocytes on MIN6 cells are ascribed to secreted bioactive factors and may be mediated via multiple pathways, which include the upregulation of UCP-2 expression via free fatty acids, and downregulation of glucokinase and Kir6.2 expression via decreasing protein tyrosine kinase activity.
1032	17709898	MIN6 cells co-cultured with 3T3-L1 adipocytes had significantly reduced intracellular calcium concentration ([Ca2+]i) and lost the ability to secrete insulin in response to tolbutamide, compared to the control cells. 3T3-L1 adipocytes significantly decreased the expression of insulin, glucokinase and Kir6.2 genes but increased the expression of uncoupling protein-2 (UCP-2) in MIN6 cells after one week of co-culture, as measured by semi-quantitative RT-PCR. 3T3-L1 adipocyte-conditioned medium also significantly decreased insulin secretion and the expression of insulin, glucokinase and Kir6.2 genes in MIN6 cells.
1033	17709898	The inhibitor of protein tyrosine kinase, genistein, decreased the expression of glucokinase and Kir6.2 in MIN6 cells, while two free fatty acids, oleic acid and linoleic acids, were found to increase UCP-2 expression.
1034	17709898	The effects of T3-L1 adipocytes on MIN6 cells are ascribed to secreted bioactive factors and may be mediated via multiple pathways, which include the upregulation of UCP-2 expression via free fatty acids, and downregulation of glucokinase and Kir6.2 expression via decreasing protein tyrosine kinase activity.
1035	17709898	MIN6 cells co-cultured with 3T3-L1 adipocytes had significantly reduced intracellular calcium concentration ([Ca2+]i) and lost the ability to secrete insulin in response to tolbutamide, compared to the control cells. 3T3-L1 adipocytes significantly decreased the expression of insulin, glucokinase and Kir6.2 genes but increased the expression of uncoupling protein-2 (UCP-2) in MIN6 cells after one week of co-culture, as measured by semi-quantitative RT-PCR. 3T3-L1 adipocyte-conditioned medium also significantly decreased insulin secretion and the expression of insulin, glucokinase and Kir6.2 genes in MIN6 cells.
1036	17709898	The inhibitor of protein tyrosine kinase, genistein, decreased the expression of glucokinase and Kir6.2 in MIN6 cells, while two free fatty acids, oleic acid and linoleic acids, were found to increase UCP-2 expression.
1037	17709898	The effects of T3-L1 adipocytes on MIN6 cells are ascribed to secreted bioactive factors and may be mediated via multiple pathways, which include the upregulation of UCP-2 expression via free fatty acids, and downregulation of glucokinase and Kir6.2 expression via decreasing protein tyrosine kinase activity.
1038	17720745	Our objective was to investigate the relationship between the E23K genetic variant in the KCNJ11 gene, which encodes for the Kir6.2 subunit of the inward rectifier K+ channel family, and glucose and insulin metabolism and cardiovascular (CV) function in the sedentary state and their responses to exercise training.
1039	17728498	Sulfonylurea therapy in two Korean patients with insulin-treated neonatal diabetes due to heterozygous mutations of the KCNJ11 gene encoding Kir6.2.
1040	17728498	Permanent neonatal diabetes (PND) is a rare form of diabetes characterized by insulin-requiring hyperglycemia diagnosed within the first three months of life.
1041	17728498	Recently, mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive K+ channel have been described in patients with PND.
1042	17728498	We report the first two Korean cases with PND due to a lysineto- arginine substitution at position 170 (K179R) and a valine-to-methionine substitution at position 59 (V59M) mutations of KCNJ11 encoding Kir6.2, respectively.
1043	17728498	These cases demonstrate that oral sulfonylurea may be the treatment of choice in PND patients with KCNJ11 mutations even at a young age.
1044	17728498	Sulfonylurea therapy in two Korean patients with insulin-treated neonatal diabetes due to heterozygous mutations of the KCNJ11 gene encoding Kir6.2.
1045	17728498	Permanent neonatal diabetes (PND) is a rare form of diabetes characterized by insulin-requiring hyperglycemia diagnosed within the first three months of life.
1046	17728498	Recently, mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive K+ channel have been described in patients with PND.
1047	17728498	We report the first two Korean cases with PND due to a lysineto- arginine substitution at position 170 (K179R) and a valine-to-methionine substitution at position 59 (V59M) mutations of KCNJ11 encoding Kir6.2, respectively.
1048	17728498	These cases demonstrate that oral sulfonylurea may be the treatment of choice in PND patients with KCNJ11 mutations even at a young age.
1049	17728498	Sulfonylurea therapy in two Korean patients with insulin-treated neonatal diabetes due to heterozygous mutations of the KCNJ11 gene encoding Kir6.2.
1050	17728498	Permanent neonatal diabetes (PND) is a rare form of diabetes characterized by insulin-requiring hyperglycemia diagnosed within the first three months of life.
1051	17728498	Recently, mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive K+ channel have been described in patients with PND.
1052	17728498	We report the first two Korean cases with PND due to a lysineto- arginine substitution at position 170 (K179R) and a valine-to-methionine substitution at position 59 (V59M) mutations of KCNJ11 encoding Kir6.2, respectively.
1053	17728498	These cases demonstrate that oral sulfonylurea may be the treatment of choice in PND patients with KCNJ11 mutations even at a young age.
1054	17728498	Sulfonylurea therapy in two Korean patients with insulin-treated neonatal diabetes due to heterozygous mutations of the KCNJ11 gene encoding Kir6.2.
1055	17728498	Permanent neonatal diabetes (PND) is a rare form of diabetes characterized by insulin-requiring hyperglycemia diagnosed within the first three months of life.
1056	17728498	Recently, mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive K+ channel have been described in patients with PND.
1057	17728498	We report the first two Korean cases with PND due to a lysineto- arginine substitution at position 170 (K179R) and a valine-to-methionine substitution at position 59 (V59M) mutations of KCNJ11 encoding Kir6.2, respectively.
1058	17728498	These cases demonstrate that oral sulfonylurea may be the treatment of choice in PND patients with KCNJ11 mutations even at a young age.
1059	17728716	To address these issues, we disrupted glucose sensing in glucose-excited pro-opiomelanocortin (POMC) neurons via transgenic expression of a mutant Kir6.2 subunit (encoded by the Kcnj11 gene) that prevents ATP-mediated closure of K(ATP) channels.
1060	17728716	The mechanism for obesity-induced loss of glucose sensing in POMC neurons involves uncoupling protein 2 (UCP2), a mitochondrial protein that impairs glucose-stimulated ATP production.
1061	17728716	UCP2 negatively regulates glucose sensing in POMC neurons.
1062	17823772	We found significant associations between eight SNPs, including the KCNJ11 E23K and ABCC8 S1369A variants, and T2D.
1063	17914241	Glycine 310 remains conserved for glucokinase and potassium channel KCNJ11.
1064	17919178	K(ATP) channels were expressed in Xenopus oocytes, and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of sulphonylurea receptor (SUR)).
1065	17919178	The E322K mutation was without effect when Kir6.2 was expressed in the absence of SUR1, suggesting that this residue impairs coupling to SUR1.
1066	17919178	K(ATP) channels were expressed in Xenopus oocytes, and the heterozygous state was simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell type of sulphonylurea receptor (SUR)).
1067	17919178	The E322K mutation was without effect when Kir6.2 was expressed in the absence of SUR1, suggesting that this residue impairs coupling to SUR1.
1068	17919182	Consistent with this paradigm, loss-of-function mutations in the genes (KCNJ11 and ABCC8) that encode the two subunits (Kir6.2 and SUR1, respectively) of the ATP-sensitive K(+) (K(ATP)) channel underlie hyperinsulinism in humans, a genetic disorder characterized by dysregulated insulin secretion.
1069	17923772	These channels are octameric complexes of 4 pore-forming Kir and 4 regulatory sulphonylurea receptor (SUR) subunits.
1070	17923772	In vitro studies showed no attenuation of ATP sensitivity but an increase in the opening probability of the channel through interaction of the mutated SUR1 subunit on Kir6.2.
1071	17923772	Sulphonylureas close KATP channels by binding with high affinity to SUR suggesting they could replace insulin in these patients.
1072	17923772	Subsequently, more than 60 patients have been reported as successfully switched from insulin subcutaneous injections to oral sulphonylurea therapy, with an improvement in their glycated hemoglobin.
1073	17931842	Among those, the very recently elucidated mutations in KCNJ11 and ABCC8 gene, encoding the Kir6.2 and SUR1 subunit of the pancreatic K(ATP) channel involved in regulation of insulin secretion accounts for one third to a half of the PNDM cases.
1074	17931842	Molecular analysis of chromosome 6 anomalies, the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1 provide a tool to identify transient from permanent neonatal diabetes mellitus in the neonatal period.
1075	17931842	This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 from insulin therapy to sulfonylureas.
1076	17931842	Among those, the very recently elucidated mutations in KCNJ11 and ABCC8 gene, encoding the Kir6.2 and SUR1 subunit of the pancreatic K(ATP) channel involved in regulation of insulin secretion accounts for one third to a half of the PNDM cases.
1077	17931842	Molecular analysis of chromosome 6 anomalies, the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1 provide a tool to identify transient from permanent neonatal diabetes mellitus in the neonatal period.
1078	17931842	This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 from insulin therapy to sulfonylureas.
1079	17931842	Among those, the very recently elucidated mutations in KCNJ11 and ABCC8 gene, encoding the Kir6.2 and SUR1 subunit of the pancreatic K(ATP) channel involved in regulation of insulin secretion accounts for one third to a half of the PNDM cases.
1080	17931842	Molecular analysis of chromosome 6 anomalies, the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1 provide a tool to identify transient from permanent neonatal diabetes mellitus in the neonatal period.
1081	17931842	This analysis also has potentially important therapeutic consequences leading to transfer some patients, those with mutations in KCNJ11 and ABCC8 from insulin therapy to sulfonylureas.
1082	17963417	Most studies involving cytochrome P450 (CYP) genes had small sample sizes (21 studies <50 subjects) and were among healthy volunteers.
1083	17963417	Polymorphisms in genes encoding the inwardly rectifying potassium channel Kir6.2 (KCNJ11) and the insulin receptor substrate-1 (IRS1) were reported to be associated with an increased risk of (secondary) failure to respond to sulfonylurea therapy.
1084	17963417	A significant decrease in fasting plasma glucose and hemoglobin A(1c) (HbA(1c)) in response to rosiglitazone was seen in subjects carrying the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma (PPARG) gene.
1085	17994213	No evidence that established type 2 diabetes susceptibility variants in the PPARG and KCNJ11 genes have pleiotropic effects on early growth.
1086	18025464	Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are a common cause of neonatal diabetes mellitus.
1087	18025464	SUR1 is a channel regulator that modulates the gating of the pore formed by Kir6.2.
1088	18025464	K(ATP) channel activity is inhibited by ATP binding to Kir6.2 but is stimulated by MgADP binding, or by MgATP binding and hydrolysis, at the NBDs of SUR1.
1089	18025464	Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are a common cause of neonatal diabetes mellitus.
1090	18025464	SUR1 is a channel regulator that modulates the gating of the pore formed by Kir6.2.
1091	18025464	K(ATP) channel activity is inhibited by ATP binding to Kir6.2 but is stimulated by MgADP binding, or by MgATP binding and hydrolysis, at the NBDs of SUR1.
1092	18025464	Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are a common cause of neonatal diabetes mellitus.
1093	18025464	SUR1 is a channel regulator that modulates the gating of the pore formed by Kir6.2.
1094	18025464	K(ATP) channel activity is inhibited by ATP binding to Kir6.2 but is stimulated by MgADP binding, or by MgATP binding and hydrolysis, at the NBDs of SUR1.
1095	18159846	Activating mutations in the KCNJ11 gene encoding the ATP-sensitive potassium-channel subunit of Kir6.2 result in the phenotype of permanent neonatal diabetes (PNDM).
1096	18162508	Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population.
1097	18221420	Outpatient transition of an infant with permanent neonatal diabetes due to a KCNJ11 activating mutation from subcutaneous insulin to oral glyburide.
1098	18221420	Until recently, most forms of permanent neonatal diabetes required lifelong subcutaneous insulin for management; however, permanent neonatal diabetes due to activating mutations in the KCNJ11 gene, which encodes the Kir6.2 protein subunit of the ATP-sensitive K+ (K(ATP)) channel, may be amenable to oral sulfonylurea therapy.
1099	18221420	We describe a case of an 18-month-old infant with permanent neonatal diabetes due to an activating KCNJ11 mutation successfully transitioned from subcutaneous insulin therapy to oral sulfonylurea therapy in the outpatient setting.
1100	18221420	Outpatient transition of an infant with permanent neonatal diabetes due to a KCNJ11 activating mutation from subcutaneous insulin to oral glyburide.
1101	18221420	Until recently, most forms of permanent neonatal diabetes required lifelong subcutaneous insulin for management; however, permanent neonatal diabetes due to activating mutations in the KCNJ11 gene, which encodes the Kir6.2 protein subunit of the ATP-sensitive K+ (K(ATP)) channel, may be amenable to oral sulfonylurea therapy.
1102	18221420	We describe a case of an 18-month-old infant with permanent neonatal diabetes due to an activating KCNJ11 mutation successfully transitioned from subcutaneous insulin therapy to oral sulfonylurea therapy in the outpatient setting.
1103	18221420	Outpatient transition of an infant with permanent neonatal diabetes due to a KCNJ11 activating mutation from subcutaneous insulin to oral glyburide.
1104	18221420	Until recently, most forms of permanent neonatal diabetes required lifelong subcutaneous insulin for management; however, permanent neonatal diabetes due to activating mutations in the KCNJ11 gene, which encodes the Kir6.2 protein subunit of the ATP-sensitive K+ (K(ATP)) channel, may be amenable to oral sulfonylurea therapy.
1105	18221420	We describe a case of an 18-month-old infant with permanent neonatal diabetes due to an activating KCNJ11 mutation successfully transitioned from subcutaneous insulin therapy to oral sulfonylurea therapy in the outpatient setting.
1106	18243136	We have identified that two cytosolic isoforms of AK, AK1 and AK5 are expressed in human islets and INS-1 cells.
1107	18243136	Elevated concentrations of glucose inhibit AK1 expression and AK1 immunoprecipitates with the Kir6.2 subunit of K-ATP.
1108	18301398	Firstly, diabetes diagnosed before 6 months of age frequently results from mutation of genes that encode Kir6.2 (ATP-sensitive inward rectifier potassium channel) or sulfonylurea receptor 1 subunits of an ATP-sensitive potassium channel, and improved glycemic control can be achieved by treatment with high-dose sulfonylureas rather than insulin.
1109	18323694	They are composed of two types of subunits; the pore subunits (Kir6.1, Kir6.2), which are members of the inwardly rectifying K+ channel family, and the regulatory subunits, the sulphonylurea receptors, which belong to the ATP-binding cassette (ABC) superfamily.
1110	18323694	The SURs are divided into two isoforms, SUR1 and SUR2, the latter was further divided into SUR2A and SUR2B.
1111	18378016	Islet Neogenesis Associated Protein (INGAP) increases pancreatic beta-cell mass and potentiates glucose-induced insulin secretion.
1112	18378016	Thereafter, gene (RT-PCR) and protein expression (Western blotting) of Foxa2, SUR1 and Kir6.2, cytoplasmic Ca(2+) ([Ca(2+)](i)), static and dynamic insulin secretion, and (86)Rb efflux were measured.
1113	18378016	INGAP-PP increased the expression levels of Kir6.2, SUR1 and Foxa2 genes, and SUR1 and Foxa2 proteins.
1114	18378016	Islet Neogenesis Associated Protein (INGAP) increases pancreatic beta-cell mass and potentiates glucose-induced insulin secretion.
1115	18378016	Thereafter, gene (RT-PCR) and protein expression (Western blotting) of Foxa2, SUR1 and Kir6.2, cytoplasmic Ca(2+) ([Ca(2+)](i)), static and dynamic insulin secretion, and (86)Rb efflux were measured.
1116	18378016	INGAP-PP increased the expression levels of Kir6.2, SUR1 and Foxa2 genes, and SUR1 and Foxa2 proteins.
1117	18497752	Activating mutations in the pore-forming Kir6.2 (KCNJ11) and regulatory sulphonylurea receptor SUR1 (ABCC8) subunits of the K(ATP) channel are a common cause of transient neonatal diabetes mellitus (TNDM).
1118	18504548	It has also led to the identification of common risk variants via candidate gene approaches (e.g. the E23K polymorphism in KCNJ11 or common variants in the MODY genes), and it has been validated by the description of the robust physiological effects conferred by polymorphisms in the TCF7L2 gene.
1119	18512226	We sequenced genes with a recognized role in monogenic forms of diabetes, including KCNJ11, ABCC8, GCK, IPF1, HNF1beta, NeuroD1 and TCF7L2, as well as a novel candidate gene, HNF6, known to be involved in hepatobiliary and pancreatic development, but did not identify mutations.
1120	18548275	Transition from insulin to sulfonylurea in a child with diabetes due to a mutation in KCNJ11 encoding Kir6.2--initial and long-term response to sulfonylurea therapy.
1121	18703018	Caveolin-1 is essential for glimepiride-induced insulin secretion in the pancreatic betaTC-6 cell line.
1122	18703018	The aim of this work was to investigate the possible role of caveolin-1 in glimepiride-induced insulin secretion.
1123	18703018	Here, we show that betaTC-6 caveolin-1 depleted cells maintained high rate of insulin secretion after KCl, but not after glucose and glimepiride stimulation.
1124	18703018	Moreover, we find a direct interaction between caveolin-1 and Kir6.2, one of the K(ATP) channel subunit.
1125	18703018	These results demonstrate that Cav-1 plays a critical role for glucose and sulfonylurea-stimulated insulin secretion.
1126	18758683	The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D).
1127	18758683	The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach.
1128	18758683	The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively.
1129	18758683	The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients.
1130	18758683	The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population.
1131	18758683	The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D).
1132	18758683	The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach.
1133	18758683	The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively.
1134	18758683	The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients.
1135	18758683	The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population.
1136	18758683	The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D).
1137	18758683	The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach.
1138	18758683	The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively.
1139	18758683	The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients.
1140	18758683	The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population.
1141	18758683	The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D).
1142	18758683	The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach.
1143	18758683	The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively.
1144	18758683	The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients.
1145	18758683	The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population.
1146	18767144	Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism.
1147	18767144	The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1 (SUR1).
1148	18767144	It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinism of infancy, while activating mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes.
1149	18767144	Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism.
1150	18767144	The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1 (SUR1).
1151	18767144	It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinism of infancy, while activating mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes.
1152	18767144	Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism.
1153	18767144	The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1 (SUR1).
1154	18767144	It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause oversecretion of insulin and result in hyperinsulinism of infancy, while activating mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes.
1155	18924582	This report confirms the superiority of sulfonylurea therapy in the treatment of PND with Kir6.2 mutations and shows sustained improved glycemic control over a 3-year follow-up period.
1156	18958766	Genetic variants in TCF7L2 and KCNJ11 genes in a Greek population with polycystic ovary syndrome.
1157	18958766	Given the phenotypic overlap between PCOS and T2DM, our objective was to investigate whether the TCF7L2 rs7903146(C/T) and the KCNJ11 E23K variants are involved in susceptibility to PCOS and related traits in a Greek population.
1158	18958766	PCOS patients and healthy controls were genotyped for the TCF7L2 and KCNJ11 variants.
1159	18958766	In addition, there were no associations observed between hormone levels and insulin resistance in PCOS carriers of TCF7L2 rs7903146 and KCNJ11 E23K variants.
1160	18958766	These data provide evidence that the rs7903146 variant of the TCF7L2 gene might influence PCOS predisposition, while no association is observed between the E23K variant of KCNJ11 and susceptibility to PCOS and related traits.
1161	18958766	Genetic variants in TCF7L2 and KCNJ11 genes in a Greek population with polycystic ovary syndrome.
1162	18958766	Given the phenotypic overlap between PCOS and T2DM, our objective was to investigate whether the TCF7L2 rs7903146(C/T) and the KCNJ11 E23K variants are involved in susceptibility to PCOS and related traits in a Greek population.
1163	18958766	PCOS patients and healthy controls were genotyped for the TCF7L2 and KCNJ11 variants.
1164	18958766	In addition, there were no associations observed between hormone levels and insulin resistance in PCOS carriers of TCF7L2 rs7903146 and KCNJ11 E23K variants.
1165	18958766	These data provide evidence that the rs7903146 variant of the TCF7L2 gene might influence PCOS predisposition, while no association is observed between the E23K variant of KCNJ11 and susceptibility to PCOS and related traits.
1166	18958766	Genetic variants in TCF7L2 and KCNJ11 genes in a Greek population with polycystic ovary syndrome.
1167	18958766	Given the phenotypic overlap between PCOS and T2DM, our objective was to investigate whether the TCF7L2 rs7903146(C/T) and the KCNJ11 E23K variants are involved in susceptibility to PCOS and related traits in a Greek population.
1168	18958766	PCOS patients and healthy controls were genotyped for the TCF7L2 and KCNJ11 variants.
1169	18958766	In addition, there were no associations observed between hormone levels and insulin resistance in PCOS carriers of TCF7L2 rs7903146 and KCNJ11 E23K variants.
1170	18958766	These data provide evidence that the rs7903146 variant of the TCF7L2 gene might influence PCOS predisposition, while no association is observed between the E23K variant of KCNJ11 and susceptibility to PCOS and related traits.
1171	18958766	Genetic variants in TCF7L2 and KCNJ11 genes in a Greek population with polycystic ovary syndrome.
1172	18958766	Given the phenotypic overlap between PCOS and T2DM, our objective was to investigate whether the TCF7L2 rs7903146(C/T) and the KCNJ11 E23K variants are involved in susceptibility to PCOS and related traits in a Greek population.
1173	18958766	PCOS patients and healthy controls were genotyped for the TCF7L2 and KCNJ11 variants.
1174	18958766	In addition, there were no associations observed between hormone levels and insulin resistance in PCOS carriers of TCF7L2 rs7903146 and KCNJ11 E23K variants.
1175	18958766	These data provide evidence that the rs7903146 variant of the TCF7L2 gene might influence PCOS predisposition, while no association is observed between the E23K variant of KCNJ11 and susceptibility to PCOS and related traits.
1176	18958766	Genetic variants in TCF7L2 and KCNJ11 genes in a Greek population with polycystic ovary syndrome.
1177	18958766	Given the phenotypic overlap between PCOS and T2DM, our objective was to investigate whether the TCF7L2 rs7903146(C/T) and the KCNJ11 E23K variants are involved in susceptibility to PCOS and related traits in a Greek population.
1178	18958766	PCOS patients and healthy controls were genotyped for the TCF7L2 and KCNJ11 variants.
1179	18958766	In addition, there were no associations observed between hormone levels and insulin resistance in PCOS carriers of TCF7L2 rs7903146 and KCNJ11 E23K variants.
1180	18958766	These data provide evidence that the rs7903146 variant of the TCF7L2 gene might influence PCOS predisposition, while no association is observed between the E23K variant of KCNJ11 and susceptibility to PCOS and related traits.
1181	18972257	Comparison of genetic risk in three candidate genes (TCF7L2, PPARG, KCNJ11) with traditional risk factors for type 2 diabetes in a population-based study--the HUNT study.
1182	18990670	The ATP-sensitive (KATP) channel is an octameric complex of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits, and it links cell metabolism to electrical activity in many cell types.
1183	18990670	Precisely how SUR1 talks to Kir6.2 remains unclear, but recent studies have identified some residues and domains that are involved in both physical and functional interactions between the two proteins.
1184	18990670	The importance of these interactions is exemplified by the fact that impaired regulation of Kir6.2 by SUR1 results in human disease, with loss-of-function SUR1 mutations causing congenital hyperinsulinism and gain-of-function SUR1 mutations leading to neonatal diabetes.
1185	18990670	This paper reviews recent data on the regulation of Kir6.2 by SUR1 and considers the molecular mechanisms by which SUR1 mutations produce disease.
1186	18990670	The ATP-sensitive (KATP) channel is an octameric complex of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits, and it links cell metabolism to electrical activity in many cell types.
1187	18990670	Precisely how SUR1 talks to Kir6.2 remains unclear, but recent studies have identified some residues and domains that are involved in both physical and functional interactions between the two proteins.
1188	18990670	The importance of these interactions is exemplified by the fact that impaired regulation of Kir6.2 by SUR1 results in human disease, with loss-of-function SUR1 mutations causing congenital hyperinsulinism and gain-of-function SUR1 mutations leading to neonatal diabetes.
1189	18990670	This paper reviews recent data on the regulation of Kir6.2 by SUR1 and considers the molecular mechanisms by which SUR1 mutations produce disease.
1190	18990670	The ATP-sensitive (KATP) channel is an octameric complex of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits, and it links cell metabolism to electrical activity in many cell types.
1191	18990670	Precisely how SUR1 talks to Kir6.2 remains unclear, but recent studies have identified some residues and domains that are involved in both physical and functional interactions between the two proteins.
1192	18990670	The importance of these interactions is exemplified by the fact that impaired regulation of Kir6.2 by SUR1 results in human disease, with loss-of-function SUR1 mutations causing congenital hyperinsulinism and gain-of-function SUR1 mutations leading to neonatal diabetes.
1193	18990670	This paper reviews recent data on the regulation of Kir6.2 by SUR1 and considers the molecular mechanisms by which SUR1 mutations produce disease.
1194	18990670	The ATP-sensitive (KATP) channel is an octameric complex of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits, and it links cell metabolism to electrical activity in many cell types.
1195	18990670	Precisely how SUR1 talks to Kir6.2 remains unclear, but recent studies have identified some residues and domains that are involved in both physical and functional interactions between the two proteins.
1196	18990670	The importance of these interactions is exemplified by the fact that impaired regulation of Kir6.2 by SUR1 results in human disease, with loss-of-function SUR1 mutations causing congenital hyperinsulinism and gain-of-function SUR1 mutations leading to neonatal diabetes.
1197	18990670	This paper reviews recent data on the regulation of Kir6.2 by SUR1 and considers the molecular mechanisms by which SUR1 mutations produce disease.
1198	18998097	The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1.
1199	18998097	Loss of function mutations in the KCNJ11 and ABCC8 genes that encode for Kir6.2 and SUR1 can cause over-secretion of insulin and result in hyperinsulinism of infancy, while gain of function mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes.Genetic testing is important for patients with hyperinsulinism or neonatal diabetes, as identification of a K(ATP) channel mutation confirms a diagnosis of their disorder.
1200	18998097	The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1.
1201	18998097	Loss of function mutations in the KCNJ11 and ABCC8 genes that encode for Kir6.2 and SUR1 can cause over-secretion of insulin and result in hyperinsulinism of infancy, while gain of function mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes.Genetic testing is important for patients with hyperinsulinism or neonatal diabetes, as identification of a K(ATP) channel mutation confirms a diagnosis of their disorder.
1202	19065048	It is commonly caused by gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of the plasmalemmal ATP-sensitive K+ (KATP) channel.
1203	19065048	Expression of the V59M Kir6.2 mutation in pancreatic beta cells alone is thus sufficient to recapitulate the neonatal diabetes observed in humans. beta-V59M islets also displayed a reduced percentage of beta cells, abnormal morphology, lower insulin content, and decreased expression of Kir6.2, SUR1, and insulin mRNA.
1204	19065048	It is commonly caused by gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of the plasmalemmal ATP-sensitive K+ (KATP) channel.
1205	19065048	Expression of the V59M Kir6.2 mutation in pancreatic beta cells alone is thus sufficient to recapitulate the neonatal diabetes observed in humans. beta-V59M islets also displayed a reduced percentage of beta cells, abnormal morphology, lower insulin content, and decreased expression of Kir6.2, SUR1, and insulin mRNA.
1206	19082521	We analysed 23 SNPs in 9 T2DM genes (CDKAL1, CDKN2B, HHEX/IDE, IGF2BP2, KCNJ11, SLC30A8, TCF2, TCF7L2 and WFS1) in a maximum of 712 men and women from the Quebec Family Study.
1207	19082521	We confirmed the significant associations of variants in CDKAL1, CDKN2B, HHEX/IDE, KCNJ11 and TCF7L2 with insulin secretion and also found associations of some of these variants with insulin sensitivity and glucose tolerance.
1208	19082521	IGF2BP2 and SLC30A8 SNPs were not associated with insulin secretion but were with insulin sensitivity and glucose tolerance (0.002 <or= P <or= 0.02).
1209	19082521	Diabetes-associated variants in CDKAL1, CDKN2B, HHEX/IDE, IGF2BP2, KCNJ11, SLC30A8 and TCF7L2 are associated with physiological alterations leading to T2DM, such as glucose intolerance, impaired insulin secretion or insulin resistance, supporting their role in the disease aetiology.
1210	19082521	We analysed 23 SNPs in 9 T2DM genes (CDKAL1, CDKN2B, HHEX/IDE, IGF2BP2, KCNJ11, SLC30A8, TCF2, TCF7L2 and WFS1) in a maximum of 712 men and women from the Quebec Family Study.
1211	19082521	We confirmed the significant associations of variants in CDKAL1, CDKN2B, HHEX/IDE, KCNJ11 and TCF7L2 with insulin secretion and also found associations of some of these variants with insulin sensitivity and glucose tolerance.
1212	19082521	IGF2BP2 and SLC30A8 SNPs were not associated with insulin secretion but were with insulin sensitivity and glucose tolerance (0.002 <or= P <or= 0.02).
1213	19082521	Diabetes-associated variants in CDKAL1, CDKN2B, HHEX/IDE, IGF2BP2, KCNJ11, SLC30A8 and TCF7L2 are associated with physiological alterations leading to T2DM, such as glucose intolerance, impaired insulin secretion or insulin resistance, supporting their role in the disease aetiology.
1214	19082521	We analysed 23 SNPs in 9 T2DM genes (CDKAL1, CDKN2B, HHEX/IDE, IGF2BP2, KCNJ11, SLC30A8, TCF2, TCF7L2 and WFS1) in a maximum of 712 men and women from the Quebec Family Study.
1215	19082521	We confirmed the significant associations of variants in CDKAL1, CDKN2B, HHEX/IDE, KCNJ11 and TCF7L2 with insulin secretion and also found associations of some of these variants with insulin sensitivity and glucose tolerance.
1216	19082521	IGF2BP2 and SLC30A8 SNPs were not associated with insulin secretion but were with insulin sensitivity and glucose tolerance (0.002 <or= P <or= 0.02).
1217	19082521	Diabetes-associated variants in CDKAL1, CDKN2B, HHEX/IDE, IGF2BP2, KCNJ11, SLC30A8 and TCF7L2 are associated with physiological alterations leading to T2DM, such as glucose intolerance, impaired insulin secretion or insulin resistance, supporting their role in the disease aetiology.
1218	19139106	Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1.
1219	19139106	beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8.
1220	19139106	Nucleotide binding to Kir6.2 inhibits channel activity, whereas ATP binding/hydrolysis on sulfonylurea receptor 1 (SUR1) opposes inhibition.
1221	19139106	Segments of the Kir6.2 N terminus are important for open-to-closed transitions, form part of the Kir ATP, sulfonylurea, and phosphoinositide binding sites, and interact with L0, an SUR cytoplasmic loop.
1222	19139106	We compared Kir6.x/SUR1 channels carrying the V59G substitution, a cause of the developmental delay, epilepsy, and neonatal diabetes syndrome, with a V59A substitution and the equivalent I60G mutation in the related Kir6.1 subunit from vascular smooth muscle.
1223	19139106	Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1.
1224	19139106	beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8.
1225	19139106	Nucleotide binding to Kir6.2 inhibits channel activity, whereas ATP binding/hydrolysis on sulfonylurea receptor 1 (SUR1) opposes inhibition.
1226	19139106	Segments of the Kir6.2 N terminus are important for open-to-closed transitions, form part of the Kir ATP, sulfonylurea, and phosphoinositide binding sites, and interact with L0, an SUR cytoplasmic loop.
1227	19139106	We compared Kir6.x/SUR1 channels carrying the V59G substitution, a cause of the developmental delay, epilepsy, and neonatal diabetes syndrome, with a V59A substitution and the equivalent I60G mutation in the related Kir6.1 subunit from vascular smooth muscle.
1228	19139106	Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1.
1229	19139106	beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8.
1230	19139106	Nucleotide binding to Kir6.2 inhibits channel activity, whereas ATP binding/hydrolysis on sulfonylurea receptor 1 (SUR1) opposes inhibition.
1231	19139106	Segments of the Kir6.2 N terminus are important for open-to-closed transitions, form part of the Kir ATP, sulfonylurea, and phosphoinositide binding sites, and interact with L0, an SUR cytoplasmic loop.
1232	19139106	We compared Kir6.x/SUR1 channels carrying the V59G substitution, a cause of the developmental delay, epilepsy, and neonatal diabetes syndrome, with a V59A substitution and the equivalent I60G mutation in the related Kir6.1 subunit from vascular smooth muscle.
1233	19139106	Analysis of two KCNJ11 neonatal diabetes mutations, V59G and V59A, and the analogous KCNJ8 I60G substitution: differences between the channel subtypes formed with SUR1.
1234	19139106	beta-Cell-type K(ATP) channels are octamers assembled from Kir6.2/KCNJ11 and SUR1/ABCC8.
1235	19139106	Nucleotide binding to Kir6.2 inhibits channel activity, whereas ATP binding/hydrolysis on sulfonylurea receptor 1 (SUR1) opposes inhibition.
1236	19139106	Segments of the Kir6.2 N terminus are important for open-to-closed transitions, form part of the Kir ATP, sulfonylurea, and phosphoinositide binding sites, and interact with L0, an SUR cytoplasmic loop.
1237	19139106	We compared Kir6.x/SUR1 channels carrying the V59G substitution, a cause of the developmental delay, epilepsy, and neonatal diabetes syndrome, with a V59A substitution and the equivalent I60G mutation in the related Kir6.1 subunit from vascular smooth muscle.
1238	19151370	Sulfonylurea receptor 1 mutations that cause opposite insulin secretion defects with chemical chaperone exposure.
1239	19151370	The beta-cell ATP-sensitive potassium (K(ATP)) channel composed of sulfonylurea receptor SUR1 and potassium channel Kir6.2 serves a key role in insulin secretion regulation by linking glucose metabolism to cell excitability.
1240	19151370	Mutations in SUR1 or Kir6.2 that decrease channel function are typically associated with congenital hyperinsulinism, whereas those that increase channel function are associated with neonatal diabetes.
1241	19151370	Further analyses revealed a nucleotide-independent decrease in mutant channel intrinsic open probability, suggesting the mutations may reduce ATP sensitivity by causing functional uncoupling between SUR1 and Kir6.2.
1242	19151370	Sulfonylurea receptor 1 mutations that cause opposite insulin secretion defects with chemical chaperone exposure.
1243	19151370	The beta-cell ATP-sensitive potassium (K(ATP)) channel composed of sulfonylurea receptor SUR1 and potassium channel Kir6.2 serves a key role in insulin secretion regulation by linking glucose metabolism to cell excitability.
1244	19151370	Mutations in SUR1 or Kir6.2 that decrease channel function are typically associated with congenital hyperinsulinism, whereas those that increase channel function are associated with neonatal diabetes.
1245	19151370	Further analyses revealed a nucleotide-independent decrease in mutant channel intrinsic open probability, suggesting the mutations may reduce ATP sensitivity by causing functional uncoupling between SUR1 and Kir6.2.
1246	19151370	Sulfonylurea receptor 1 mutations that cause opposite insulin secretion defects with chemical chaperone exposure.
1247	19151370	The beta-cell ATP-sensitive potassium (K(ATP)) channel composed of sulfonylurea receptor SUR1 and potassium channel Kir6.2 serves a key role in insulin secretion regulation by linking glucose metabolism to cell excitability.
1248	19151370	Mutations in SUR1 or Kir6.2 that decrease channel function are typically associated with congenital hyperinsulinism, whereas those that increase channel function are associated with neonatal diabetes.
1249	19151370	Further analyses revealed a nucleotide-independent decrease in mutant channel intrinsic open probability, suggesting the mutations may reduce ATP sensitivity by causing functional uncoupling between SUR1 and Kir6.2.
1250	19169493	We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11.
1251	19214942	We investigated the effects of the E23K variant of KCNJ11 (potassium inwardly-rectifying channel, subfamily J, member 11) on risk for SH in patients with type 2 diabetes (T2D).
1252	19214942	Our data suggest that patients with T2D carrying the K variant of the E23K polymorphism in KCNJ11 have reduced response to sulfonylurea therapy, which results in increased HbA(1c) and consequently in lower risk for SH.
1253	19214942	We investigated the effects of the E23K variant of KCNJ11 (potassium inwardly-rectifying channel, subfamily J, member 11) on risk for SH in patients with type 2 diabetes (T2D).
1254	19214942	Our data suggest that patients with T2D carrying the K variant of the E23K polymorphism in KCNJ11 have reduced response to sulfonylurea therapy, which results in increased HbA(1c) and consequently in lower risk for SH.
1255	19233137	The effects of E23K polymorphism in Kir6.2 subunit on insulin sensitivity in skeletal muscle cells by long-chain fatty acyl CoA.
1256	19233137	LC-CoA also reduced IRS-1 and Akt phosphorylation and glucose transport.
1257	19247372	We then selected 11 genes, KCNQ1, TCF7L2, CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX, GCKR, HNF1B, KCNJ11 and PPARG, whose associations with diabetes have already been reported and replicated either in the literature or in this study in the Japanese population.
1258	19247925	Transfer from insulin to sulfonylurea treatment in a chinese patient with permanent neonatal diabetes mellitus due to a KCNJ11 R201H mutation.
1259	19273354	An aetiological approach has identified monogenic patients with diabetes due to TCF1 mutations who are particularly sensitive to the hypoglycaemic effects of sulphonylureas, and KCNJ11 or ABCC8 mutations in which sulphonylureas can be used in place of insulin treatment.
1260	19496967	Permanent neonatal diabetes mellitus is a rare disorder known to be caused by activating mutations in KCNJ11 or ABCC8, inactivating mutations in INS, or very rarely in GCK or insulin promotor factor-1 (IPF-1) genes.
1261	19498446	The genes (ABCC8 and KCNJ11) have a key role in glucose-stimulated insulin secretion and thus have always been considered as excellent susceptibility candidates for involvement in type 2 diabetes.
1262	19521719	We identified no mutations in ZFP57, KCNJ11, ABCC8, GCK, HNF1A, HNF1B, HNF3B, IPF1, PAX4, or ZIC3.
1263	19521719	The proband had loss of methylation at the 6q24 locus TNDM and also at the loci IGF2R, DIRAS3, and PEG1, while the other family members, including the healthy monozygotic twin, had normal findings.
1264	19656320	Successful sulfonylurea treatment of an insulin-naïve neonate with diabetes mellitus due to a KCNJ11 mutation.
1265	19656320	A K(ATP) mutation (R201H; KCNJ11) was detected in the infant, the mother, and 6-yr-old sister with PNDM; both were also subsequently transitioned off insulin onto glyburide.
1266	19656320	Successful sulfonylurea treatment of an insulin-naïve neonate with diabetes mellitus due to a KCNJ11 mutation.
1267	19656320	A K(ATP) mutation (R201H; KCNJ11) was detected in the infant, the mother, and 6-yr-old sister with PNDM; both were also subsequently transitioned off insulin onto glyburide.
1268	19686306	Medical and developmental impact of transition from subcutaneous insulin to oral glyburide in a 15-yr-old boy with neonatal diabetes mellitus and intermediate DEND syndrome: extending the age of KCNJ11 mutation testing in neonatal DM.
1269	19766903	Metabolic control in type 2 diabetes is associated with sulfonylurea receptor-1 (SUR-1) but not with KCNJ11 polymorphisms.
1270	19774848	Activating mutations of the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-dependent potassium channel in beta-cells, have been found to cause 30-58% of cases of PND.
1271	19799532	CYP2C19 genotype is more influential for gliclazide pharmacokinetics when compared to CYP2C9.
1272	19799532	Sulfonylurea receptor 1 (SUR1, ABCC8 gene) and K+ inward rectifier Kir6.2 (KCNJ11) have been correlated to significant variation in sulfonylurea response.
1273	19799532	Diabetics with the SUR1 exon 33 G allele are more sensitive to gliclazide and the rs5210 variant of the KCNJ11 gene was associated with improved clinical efficacy of gliclazide.
1274	19799532	Carriers of Transcription factor 7-like 2 (TCF7L2) variants are more likely to fail sulfonylurea therapy.
1275	19799532	CYP2C19 genotype is more influential for gliclazide pharmacokinetics when compared to CYP2C9.
1276	19799532	Sulfonylurea receptor 1 (SUR1, ABCC8 gene) and K+ inward rectifier Kir6.2 (KCNJ11) have been correlated to significant variation in sulfonylurea response.
1277	19799532	Diabetics with the SUR1 exon 33 G allele are more sensitive to gliclazide and the rs5210 variant of the KCNJ11 gene was associated with improved clinical efficacy of gliclazide.
1278	19799532	Carriers of Transcription factor 7-like 2 (TCF7L2) variants are more likely to fail sulfonylurea therapy.
1279	19862325	PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.
1280	19933268	The function of the ATP-sensitive potassium (K(ATP)) channel relies on the proper coupling between its two subunits: the pore-forming Kir6.2 and the regulator SUR.
1281	19933268	The conformation of the interface between these two subunits can be monitored using a rhodamine 123 (Rho) protection assay because Rho blocks Kir6.2 with an efficiency that depends on the relative position of transmembrane domain (TMD) 0 of the associated SUR (Hosy, E., Dérand, R., Revilloud, J., and Vivaudou, M. (2007) J.
1282	19933268	The function of the ATP-sensitive potassium (K(ATP)) channel relies on the proper coupling between its two subunits: the pore-forming Kir6.2 and the regulator SUR.
1283	19933268	The conformation of the interface between these two subunits can be monitored using a rhodamine 123 (Rho) protection assay because Rho blocks Kir6.2 with an efficiency that depends on the relative position of transmembrane domain (TMD) 0 of the associated SUR (Hosy, E., Dérand, R., Revilloud, J., and Vivaudou, M. (2007) J.
1284	20022885	Gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of this channel cause neonatal diabetes.
1285	20033705	Assembly of an inward rectifier K+ channel pore (Kir6.1/Kir6.2) and an adenosine triphosphate (ATP)-binding regulatory subunit (SUR1/SUR2A/SUR2B) forms ATP-sensitive K+ (KATP) channel heteromultimers, widely distributed in metabolically active tissues throughout the body.
1286	20042013	Several molecular mechanisms are involved in the development of CHI, but the most common genetic defects are inactivating mutations of the ABCC8 or KCNJ11 genes.
1287	20049716	Loss- and gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of this channel cause hyperinsulinism of infancy and neonatal diabetes, respectively.
1288	20054294	KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) polymorphisms affect therapeutic efficacy of repaglinide in Chinese patients with type 2 diabetes.
1289	20054294	This study showed that the polymorphisms KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) are associated with a heightened risk of developing type 2 diabetes mellitus (T2DM).
1290	20054294	After repaglinide treatment, patients with the GA or AA genotype showed higher levels of FPG, PPG, and glycated hemoglobin (HbA(1c)) compared with patients with the GG genotype (P < 0.05).
1291	20054294	The KCNJ11 and TCF7L2 polymorphisms were associated with repaglinide efficacy.
1292	20054294	KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) polymorphisms affect therapeutic efficacy of repaglinide in Chinese patients with type 2 diabetes.
1293	20054294	This study showed that the polymorphisms KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) are associated with a heightened risk of developing type 2 diabetes mellitus (T2DM).
1294	20054294	After repaglinide treatment, patients with the GA or AA genotype showed higher levels of FPG, PPG, and glycated hemoglobin (HbA(1c)) compared with patients with the GG genotype (P < 0.05).
1295	20054294	The KCNJ11 and TCF7L2 polymorphisms were associated with repaglinide efficacy.
1296	20054294	KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) polymorphisms affect therapeutic efficacy of repaglinide in Chinese patients with type 2 diabetes.
1297	20054294	This study showed that the polymorphisms KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) are associated with a heightened risk of developing type 2 diabetes mellitus (T2DM).
1298	20054294	After repaglinide treatment, patients with the GA or AA genotype showed higher levels of FPG, PPG, and glycated hemoglobin (HbA(1c)) compared with patients with the GG genotype (P < 0.05).
1299	20054294	The KCNJ11 and TCF7L2 polymorphisms were associated with repaglinide efficacy.
1300	20079163	Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population.
1301	20082465	Investigations included sequencing of GCK, ABCC8, IPF1, NEUROD1, PTF1A, HNF1B, INS, ISL1, NGN3, HHEX, G6PC2, TCF7L2, SOX4, FOXP3 (Patients 1 and 2), GATA4 and KCNJ11 genes (all three patients), but no mutations were found.
1302	20092027	Genetic analysis was negative for mutations of KCNJ11, 6q24, Glucokinase and IPF-1 genes.
1303	20142250	We evaluated associations in the Atherosclerosis Risk in Communities study between PrCa and nine T2D single nucleotide polymorphisms from genome-wide association studies of T2D (in CDKAL1, CDKN2A/B, FTO, HHEX, IGF2BP2, KCNJ11, PPARG, SLC30A8, and TCF7L2) and four T2D single nucleotide polymorphisms from pre-genome-wide association studies (in ADRB2, CAPN10, SLC2A2, and UCP2).
1304	20142250	PrCa was positively associated with the CAPN10 rs3792267 G allele [hazard ratio (HR) 1.20; 95% confidence interval (CI), 1.00-1.44] and inversely associated with the SLC2A2 rs5400 Thr110 allele (HR, 0.85; 95% CI, 0.72, 1.00), the UCP2 rs660339 Val55 allele (HR, 0.84; 95% CI, 0.73, 0.97) and the IGF2BP2 rs4402960 T allele (HR, 0.79; 95% CI, 0.61-1.02; blacks only).
1305	20157388	On immunohistochemistry analysis for the Kir6.2 subunit of K(ATP) channels, insulin receptor beta-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats.
1306	20220270	Successful transfer from insulin to oral sulfonylurea in a 3-year-old girl with a mutation in the KCNJ11 gene.
1307	20220270	We describe a 3-year-old girl with permanent neonatal diabetes mellitus with a mutation in the KCNJ11 gene (R201H), who was successfully transferred from subcutaneous insulin to oral glibenclamide, with a marked improvement in glycemic control.
1308	20220270	Successful transfer from insulin to oral sulfonylurea in a 3-year-old girl with a mutation in the KCNJ11 gene.
1309	20220270	We describe a 3-year-old girl with permanent neonatal diabetes mellitus with a mutation in the KCNJ11 gene (R201H), who was successfully transferred from subcutaneous insulin to oral glibenclamide, with a marked improvement in glycemic control.
1310	20424228	Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians.
1311	20466780	Sulfonylureas (SUs) were proven to be more effective than insulin in most Kir6.2 permanent neonatal diabetes mellitus (PNDM) patients.
1312	20466780	SUs, which seem to constitute an alternative to insulin during pregnancy in Kir6.2-related PNDM, were used during the conception period and most of the second and third trimesters.
1313	20466780	Sulfonylureas (SUs) were proven to be more effective than insulin in most Kir6.2 permanent neonatal diabetes mellitus (PNDM) patients.
1314	20466780	SUs, which seem to constitute an alternative to insulin during pregnancy in Kir6.2-related PNDM, were used during the conception period and most of the second and third trimesters.
1315	20805377	Comment on: Chauhan et al. (2010) Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians.
1316	20878272	In this review we describe the progress that has been made to date in translating association signals into molecular mechanisms with a focus on the most tractable signals (eg, KCNJ11/ABCC8, SLC30A8, GCKR) and those in which human, animal, and cellular models (FTO, TCF7L2, G6PC2) have provided insights into the role in T2D pathogenesis.
1317	20878482	The β-cell K(ATP) channel is a hetero-octameric complex composed of two types of subunits: four inward-rectifying potassium channel pore-forming (Kir6.2) subunits and four high-affinity sulfonylurea receptor 1 (SUR1) subunits.
1318	20878482	Kir6.2 and SUR1 are encoded by the genes KCNJ11 and ABCC8, respectively.
1319	20878482	The β-cell K(ATP) channel is a hetero-octameric complex composed of two types of subunits: four inward-rectifying potassium channel pore-forming (Kir6.2) subunits and four high-affinity sulfonylurea receptor 1 (SUR1) subunits.
1320	20878482	Kir6.2 and SUR1 are encoded by the genes KCNJ11 and ABCC8, respectively.
1321	20879971	These genes include glucokinase (GCK), HLA antigens, insulin receptor (INSR), insulin-like growth factor-2 (IGF2), HNF4A, insulin gene (INS-VNTR), plasminogen activator inhibitor 1 (PAI-1), potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11), hepatocyte nuclear factor-4a (HNF4A).
1322	20922570	Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11.
1323	20922570	The ATP-sensitive potassium (K(ATP)) channel is composed of two subunits SUR1 and Kir6.2.
1324	20922570	Activating mutations have been identified in the genes encoding these subunits, ABCC8 and KCNJ11, and account for approximately 40% of permanent neonatal diabetes cases.
1325	20922570	Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11.
1326	20922570	The ATP-sensitive potassium (K(ATP)) channel is composed of two subunits SUR1 and Kir6.2.
1327	20922570	Activating mutations have been identified in the genes encoding these subunits, ABCC8 and KCNJ11, and account for approximately 40% of permanent neonatal diabetes cases.
1328	20922570	Permanent neonatal diabetes due to activating mutations in ABCC8 and KCNJ11.
1329	20922570	The ATP-sensitive potassium (K(ATP)) channel is composed of two subunits SUR1 and Kir6.2.
1330	20922570	Activating mutations have been identified in the genes encoding these subunits, ABCC8 and KCNJ11, and account for approximately 40% of permanent neonatal diabetes cases.
1331	20938745	This is especially true for patients with mutations in the genes KCNJ11 or ABCC8 that encode the two protein subunits (Kir6.2 and SUR1, respectively) of the ATP-sensitive potassium channel.
1332	21056492	We describe a female neonate who is a heterozygous for a new missense mutation, V252L, in the KCNJ11 gene and who has been successfully transitioned from insulin to sulfonylurea therapy.
1333	21119644	Here, we applied Sanger sequencing of genomic PCR amplicons to resequence the diabetes-associated genes KCNJ11 and HHEX in 13,715 people (10,422 European Americans and 3,293 African Americans) and validated amplicons potentially harbouring rare variants using 454 pyrosequencing.
1334	21169132	Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to be predisposed to type 2 diabetes mellitus across many large studies.
1335	21169132	Other classes are also mentioned in literature.In this work, different types of genetic mutations (mutations of the gene for glucokinase, HNF 1α, HNF1β and Kir6.2 and SUR1 subunit of KATP channel, PPAR-γ, OCT1 and OCT2, cytochromes, direct drug-receptor (KCNJ11), as well as the factors that influence the development of the disease (TCF7L2) and variants of genes that lead to hepatosteatosis caused by thiazolidinediones) and their influence on the response to therapy with oral antidiabetics will be reviewed.
1336	21169132	Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to be predisposed to type 2 diabetes mellitus across many large studies.
1337	21169132	Other classes are also mentioned in literature.In this work, different types of genetic mutations (mutations of the gene for glucokinase, HNF 1α, HNF1β and Kir6.2 and SUR1 subunit of KATP channel, PPAR-γ, OCT1 and OCT2, cytochromes, direct drug-receptor (KCNJ11), as well as the factors that influence the development of the disease (TCF7L2) and variants of genes that lead to hepatosteatosis caused by thiazolidinediones) and their influence on the response to therapy with oral antidiabetics will be reviewed.
1338	21436302	To date, these approaches have only identified two loci (PPARG, KCNJ11) robustly implicated in T2D susceptibility.
1339	21463240	Mutations in the GCK gene cause a mild form of diabetes, which seldom needs insulin and has a low risk for complications.
1340	21463240	The majority of neonatal diabetes cases are caused by mutations in the K(ATP) channel genes ABCC8 and KCNJ11, and sulfonylurea therapy is then usually superior to insulin.
1341	21515691	Western blot, RT-PCR, and immunohistochemistry showed expression of the major genes involved in proinsulin processing and the pancreatic beta cell stimulus-secretion pathway including PC1/3, PC2, GLUT-1, glucokinase, and K-ATP channel complex (Sur1 and Kir6.2) and the voltage-dependent L-type Ca(2+) channel.
1342	21540348	A conserved tryptophan at the membrane-water interface acts as a gatekeeper for Kir6.2/SUR1 channels and causes neonatal diabetes when mutated.
1343	21540348	Replacement with tyrosine (Y) rendered the KATP channel almost completely insensitive to ATP block, dramatically increased the channel open probability, and affected the interaction of Kir6.2 with SUR1.
1344	21540348	A conserved tryptophan at the membrane-water interface acts as a gatekeeper for Kir6.2/SUR1 channels and causes neonatal diabetes when mutated.
1345	21540348	Replacement with tyrosine (Y) rendered the KATP channel almost completely insensitive to ATP block, dramatically increased the channel open probability, and affected the interaction of Kir6.2 with SUR1.
1346	21550079	Genotype risk score was calculated by the following variants, namely, KCNQ1, TCF7L2, CDKAL1, HHEX, IGF2BP2, CDKN2AB, SLC30A8, KCNJ11, PPARG, and GCKR.
1347	21573802	A number of studies have been performed to identify the association between potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene and type 2 diabetes mellitus (T2DM) in East Asian populations, with inconsistent results.
1348	21671119	In COS-7 cells triple transfected with SUR1Δ2/SUR1/Kir6.2, the SUR1Δ2 peptide co-immunoprecipitated with Kir6.2, thereby displacing two of four SUR1 subunits on the cell surface.
1349	21671119	A non-mutagenic SNP on nucleotide position 333 (Pro69Pro) added another exonic splicing enhancer sequence detected by ASF/SF2, reduced relative abundance of SUR1Δ2 and slightly protected from non-insulin dependent diabetes in homozygotic individuals.
1350	21674179	Hyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8/KCNJ11 mutations.
1351	21710463	These findings provided evidence that the KCNJ11 gene plays a role in the pathogenesis of decreased insulin sensitivity in essential hypertension patients.
1352	21796147	Recently, permanent neonatal diabetes resulting from mutations in the two protein subunits of the adenosine triphosphate-sensitive potassium channel (Kir6.2 and SUR1) has proven to be successfully treatable with high doses of sulfonylureas rather than insulin.
1353	21812222	Understanding of physiopathology increased this last decade, as many mutations in genes playing critical roles in the development of pancreas, have been described: the most common are chromosome 6q anomalies in the case of TND, and mutations in KCNJ11 and ABCC8 genes encoding the subunit of the insulin cell potassium channel in the case of PND.
1354	21814221	We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects.
1355	21814221	Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 × 10(-4)).
1356	21814221	We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects.
1357	21814221	Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 × 10(-4)).
1358	21823539	Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50%-60% of the patients.
1359	21863614	Genes KCNJ11 and ABCC8 encode potassium channel proteins.
1360	21863614	KCNJ11 gene Glu23Lys polymorphism was associated with an increased risk of SU secondary failure, while Ser1369Ala polymorphism of ABCC8 gene had influence antidiabetic efficacy of SU drug gliclazide.
1361	21863614	Genes KCNJ11 and ABCC8 encode potassium channel proteins.
1362	21863614	KCNJ11 gene Glu23Lys polymorphism was associated with an increased risk of SU secondary failure, while Ser1369Ala polymorphism of ABCC8 gene had influence antidiabetic efficacy of SU drug gliclazide.
1363	21871684	Mother and daughter carrying the same KCNJ11 mutation but with a different response to switching from insulin to sulfonylurea.
1364	21871684	We report a 18-month follow-up of switching from insulin to SU in a mother and her daughter with PNDM due to KCNJ11 mutation.
1365	21871684	Mother and daughter carrying the same KCNJ11 mutation but with a different response to switching from insulin to sulfonylurea.
1366	21871684	We report a 18-month follow-up of switching from insulin to SU in a mother and her daughter with PNDM due to KCNJ11 mutation.
1367	21953423	Patients referred to the Italian reference laboratory for NDM between years 2005 and 2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed.
1368	21953423	In this group, a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified.
1369	21953423	Patients referred to the Italian reference laboratory for NDM between years 2005 and 2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed.
1370	21953423	In this group, a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified.
1371	21959939	Some of these gene polymorphisms were identified in the genes encoding the KATP channel (KCNJ11 and ABCC8).
1372	21993633	The most common causes accounting for the majority of cases are mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel (K(ATP)), KCNJ11 and ABCC8, and the insulin gene (INS), as well as abnormalities in chromosome 6q24.
1373	21993633	Patients with activating mutations in KCNJ11 and ABCC8 can be treated with oral sulfonylureas in lieu of insulin injections.
1374	21993633	The most common causes accounting for the majority of cases are mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel (K(ATP)), KCNJ11 and ABCC8, and the insulin gene (INS), as well as abnormalities in chromosome 6q24.
1375	21993633	Patients with activating mutations in KCNJ11 and ABCC8 can be treated with oral sulfonylureas in lieu of insulin injections.
1376	22020219	Here we show that a diabetogenic mutation in an unexplored helix preceding the ABC core of SUR1 dramatically increases open probability of (SUR1/Kir6.2)(4) channel (KATP) by reciprocally changing rates of its transitions to and from the long-lived, inhibitory ligand-stabilized closed state.
1377	22020219	This kinetic mechanism attenuates ATP and sulfonylurea inhibition, but not Mg-nucleotide stimulation, of SUR1/Kir6.2.
1378	22020219	Here we show that a diabetogenic mutation in an unexplored helix preceding the ABC core of SUR1 dramatically increases open probability of (SUR1/Kir6.2)(4) channel (KATP) by reciprocally changing rates of its transitions to and from the long-lived, inhibitory ligand-stabilized closed state.
1379	22020219	This kinetic mechanism attenuates ATP and sulfonylurea inhibition, but not Mg-nucleotide stimulation, of SUR1/Kir6.2.
1380	22118586	Giving insights to beta cell function, CHI mutations are now known in eight genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2).
1381	22231386	The molecular basis of HH involves defects in key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) which regulate insulin secretion.
1382	22231386	The most severe forms of HH are due to loss of function mutations in ABCC8/KCNJ11 which encode the SUR1 and KIR6.2 components respectively of the pancreatic β-cell K(ATP) channel.
1383	22231386	The molecular basis of HH involves defects in key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) which regulate insulin secretion.
1384	22231386	The most severe forms of HH are due to loss of function mutations in ABCC8/KCNJ11 which encode the SUR1 and KIR6.2 components respectively of the pancreatic β-cell K(ATP) channel.
1385	22310720	Pancreatic specific genes were turned on, such as transcription factors (Pdx-1, Ngn3 and Nkx6.1), genes related to endocrine function (Glut-2 and PC2) or β cell function (Kir6.2, SUR1).
1386	22389004	T2D variants were associated with PCOS phenotype parameters including those in THADA and WFS1 with testosterone levels, ENPP/PC1 with triglyceride levels, FTO with glucose levels and KCNJ11 with FSH levels.
1387	22438186	A SNP in G6PC2 predicts insulin secretion in type 1 diabetes.
1388	22438186	Patients were genotyped for SNPs related to glucose metabolism: CDKAL1 rs7754840, G6PC2 rs560887, HHEX rs1111875, KCNJ11 rs5215.
1389	22438186	In a longitudinal survival analysis, homozygosity for the minor allele (A) in G6PC2 predicted more rapid loss of insulin secretion over time.
1390	22438186	A SNP in the beta cell gene G6PC2 may correlate with preserved insulin secretion in type 1 diabetes.
1391	22443257	Polycystic ovary syndrome is not associated with polymorphisms of the TCF7L2, CDKAL1, HHEX, KCNJ11, FTO and SLC30A8 genes.
1392	22451668	K(ATP) channels, (SUR1/Kir6.2)(4) (sulfonylurea receptor type 1/potassium inward rectifier type 6.2) respond to the metabolic state of pancreatic β-cells, modulating membrane potential and insulin exocytosis.
1393	22451668	K(ATP) channels are inhibited by ATP binding to the Kir6.2 pore and stimulated, via an uncertain mechanism, by magnesium nucleotides at SUR1.
1394	22451668	K(ATP) channels, (SUR1/Kir6.2)(4) (sulfonylurea receptor type 1/potassium inward rectifier type 6.2) respond to the metabolic state of pancreatic β-cells, modulating membrane potential and insulin exocytosis.
1395	22451668	K(ATP) channels are inhibited by ATP binding to the Kir6.2 pore and stimulated, via an uncertain mechanism, by magnesium nucleotides at SUR1.
1396	22492527	Variants near TCF7L2 and ADRA2A were associated with reduced glucose-induced insulin secretion, whereas susceptibility variants near ADRA2A, KCNJ11, KCNQ1, and TCF7L2 were associated with reduced depolarization-evoked insulin exocytosis.
1397	22492527	KCNQ1, ADRA2A, KCNJ11, HHEX/IDE, and SLC2A2 variants affected granule docking.
1398	22492527	Variants near TCF7L2 and ADRA2A were associated with reduced glucose-induced insulin secretion, whereas susceptibility variants near ADRA2A, KCNJ11, KCNQ1, and TCF7L2 were associated with reduced depolarization-evoked insulin exocytosis.
1399	22492527	KCNQ1, ADRA2A, KCNJ11, HHEX/IDE, and SLC2A2 variants affected granule docking.
1400	22583123	Association of TCF7L2 and ADIPOQ with body mass index, waist-hip ratio, and systolic blood pressure in an endogamous ethnic group of India.
1401	22583123	The present study tested the association of TCF7L2, HHEX, KCNJ11, and ADIPOQ with BMI, SBP, and WHR in men and women of the Aggarwal population of India and found a differential association of TCF7L2 (rs7903146, rs4506565, and rs12256372) and ADIPOQ (rs2241766 and rs1501299) genes with increasing BMI, SBP, and WHR between the two sexes.
1402	22583123	We conclude that TCF7L2 and ADIPOQ together might play an important role in explaining these traits and to understand the biological and genetic mechanisms underlying T2D, and the role of other T2D genes must also be evaluated with these continuous traits.
1403	22701567	Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene.
1404	22749234	Contribution of common variants of ENPP1, IGF2BP2, KCNJ11, MLXIPL, PPARγ, SLC30A8 and TCF7L2 to the risk of type 2 diabetes in Lebanese and Tunisian Arabs.
1405	22778220	We identified in Pax6 knockdown model that genes involved in glucagon secretion such as the glucokinase (GCK), G protein-coupled receptor (GPR40), and GIP receptor (GIPR) as well as the corresponding proteins were significantly decreased whereas the insulin receptor (IR) Kir6.2/Sur1, and glucose transporter 1 genes were not affected.
1406	22778220	We demonstrated that Pax6 directly binds and activates specific elements on the promoter region of the GPR40, GCK, and GIPR genes.
1407	22778220	Finally, through site-directed mutagenesis experiments, we showed that disruption of Pax6 binding on the GCK, GPR40, and GIPR gene promoters led to specific decreases of their activities in the αTC1.9 glucagon-producing cell line.
1408	22778220	Hence our results indicate that Pax6 acts on the regulation of glucagon secretion at least through the transcriptional control of GCK, GPR40, and GIPR.
1409	22796691	Most cases of permanent form of neonatal diabetes mellitus (PNDM) are due to dominant heterozygous gain of function (activating) mutations in either KCNJ11 or ABCC8 genes, that code for Kir 6.2 and SUR1 subunits, respectively of the pancreatic b cell KATP channel.
1410	22815030	The majority of neonatal DM cases are caused by a heterozygous activating mutation in the KCNJ11 or ABCC8 genes that encode the Kir6.2 and SUR1 protein subunits, respectively, in the KATP channel.
1411	22815030	For patients with KCNJ11 and ABCC8 gene mutation, oral sulphonylurea should be considered.
1412	22815030	The majority of neonatal DM cases are caused by a heterozygous activating mutation in the KCNJ11 or ABCC8 genes that encode the Kir6.2 and SUR1 protein subunits, respectively, in the KATP channel.
1413	22815030	For patients with KCNJ11 and ABCC8 gene mutation, oral sulphonylurea should be considered.
1414	22842804	There have been several reports of the successful transition from insulin to sulfonylurea agents in patients with permanent diabetes mellitus caused by mutations in the KCNJ11 gene.
1415	22842804	We report on a term female neonate with a novel missense mutation, p.P1199L, in the ABCC8 gene that encodes the sulfonylurea receptor 1 whose treatment was successfully converted from insulin to sulfonylurea.
1416	22923468	Twenty-four single nucleotide polymorphisms (SNPs) in or near genes (KCNJ11, PPARG, TCF7L2, SLC30A8, HHEX, CDKN2A/2B, CDKAL1, IGF2BP2, ARHGEF11, JAZF1, CDC123/CAMK1D, FTO, TSPAN8/LGR5, KCNQ1, THADA, ADAMTS9, NOTCH2, NXPH1, RORA, UBQLNL, and RALGPS2) were genotyped in Mexican Mestizos.
1417	22923468	Association to type 2 diabetes was found for rs13266634 (SLC30A8), rs7923837 (HHEX), rs10811661 (CDKN2A/2B), rs4402960 (IGF2BP2), rs12779790 (CDC123/CAMK1D), and rs2237892 (KCNQ1).
1418	22923468	In addition, rs7754840 (CDKAL1) was associated in the nonobese type 2 diabetic subgroup, and for rs7903146 (TCF7L2), association was observed for early-onset type 2 diabetes.
1419	22957706	Identification of INS and KCNJ11 gene mutations in type 1B diabetes in Japanese children with onset of diabetes before 5 years of age.
1420	23054005	Potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) E23K gene polymorphism has been indicated as relevant to type 2 diabetes mellitus (T2D) susceptibility, but research results remain debatable.To investigate the relationship between KCNJ11 E23K gene polymorphism and T2D in the Chinese Han population, a meta-analysis involving 3,080 T2D patients and 3,029 controls from five separate studies was conducted.
1421	23181120	The mRNA levels of the glucose-stimulated insulin secretion (GSIS) genes glucokinase, glucose transporter 2 and Kir6.2 were downregulated under co-culture and co-culture plus LA conditions.
1422	23181120	The mRNA levels of superoxide dismutase and catalase were reduced under co-culture conditions and these reductions were eliminated by the addition of LA.
1423	23226049	Mutations in the KCNJ11 and ABCC8 genes, encoding the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel Kir6.2 and SUR1 subunits, respectively, are found in ∼50% of NDM patients.
1424	23226049	In the pancreatic β-cell, K(ATP) channel activity couples glucose metabolism to insulin secretion via cellular excitability and mutations in either KCNJ11 or ABCC8 genes alter K(ATP) channel activity, leading to faulty insulin secretion.
1425	23226049	Many NDM patients with KCNJ11 and ABCC8 mutations can be successfully treated with sulfonylureas (SUs) that inhibit the K(ATP) channel, thus replacing the need for daily insulin injections.
1426	23226049	Mutations in the KCNJ11 and ABCC8 genes, encoding the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel Kir6.2 and SUR1 subunits, respectively, are found in ∼50% of NDM patients.
1427	23226049	In the pancreatic β-cell, K(ATP) channel activity couples glucose metabolism to insulin secretion via cellular excitability and mutations in either KCNJ11 or ABCC8 genes alter K(ATP) channel activity, leading to faulty insulin secretion.
1428	23226049	Many NDM patients with KCNJ11 and ABCC8 mutations can be successfully treated with sulfonylureas (SUs) that inhibit the K(ATP) channel, thus replacing the need for daily insulin injections.
1429	23226049	Mutations in the KCNJ11 and ABCC8 genes, encoding the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel Kir6.2 and SUR1 subunits, respectively, are found in ∼50% of NDM patients.
1430	23226049	In the pancreatic β-cell, K(ATP) channel activity couples glucose metabolism to insulin secretion via cellular excitability and mutations in either KCNJ11 or ABCC8 genes alter K(ATP) channel activity, leading to faulty insulin secretion.
1431	23226049	Many NDM patients with KCNJ11 and ABCC8 mutations can be successfully treated with sulfonylureas (SUs) that inhibit the K(ATP) channel, thus replacing the need for daily insulin injections.
1432	23350652	We report a rare case of permanent neonatal diabetes (PND) due to insulin (INS) gene mutation in a 51-month-old girl who presented with hyperglycemia in the neonatal period.
1433	23350652	Mutational analysis of KCNJ11 and INS was performed and this detected a novel heterozygous c.38T>G (p.Leu13Arg) INS de novo mutation.
1434	23434183	Unsuccessful switch from insulin to sulfonylurea therapy in permanent neonatal diabetes mellitus due to an R201H mutation in the KCNJ11 gene: a case report.
1435	23434183	Previously, all patients carrying an R201H mutation in the KCNJ11 gene showed successful switches from insulin to sulfonylurea.
1436	23434183	Unsuccessful switch from insulin to sulfonylurea therapy in permanent neonatal diabetes mellitus due to an R201H mutation in the KCNJ11 gene: a case report.
1437	23434183	Previously, all patients carrying an R201H mutation in the KCNJ11 gene showed successful switches from insulin to sulfonylurea.
1438	23449893	The cultured infant islets expressed pancreatic and duodenal homeobox 1 and several (Glut1, Cav1.3, Kir6.2) but not all (syntaxin 1A and synaptosomal-associated protein 25) markers of functional islets, suggesting a loss of secretory phenotype in culture.
1439	23449893	After a 24- to 28-day expansion and maturation protocol, we found preservation of endocrine markers and hormone expression, an increased proportion of insulin-positive cells, elevated expression of syntaxin 1A and synaptosomal-associated protein 25, and restoration of exocytosis to levels comparable with that in adult β-cells.
1440	23557703	Carriers of risk variants in BCL11A, HHEX, ZBED3, HNF1A, IGF1, and NOTCH2 showed elevated whereas those in CRY2, IGF2BP2, TSPAN8, and KCNJ11 showed decreased fasting and/or 2-h glucagon concentrations in vivo.
1441	23557703	Variants in BCL11A, TSPAN8, and NOTCH2 affected glucagon secretion both in vivo and in vitro.
1442	23557703	The MTNR1B variant was a clear outlier in the relationship analysis between insulin secretion and action, as well as between insulin, glucose, and glucagon.
1443	23608551	Continue with long term sulfonylureas in patients with mutations in the KCNJ11 gene when there is evidence of response even if insulin treatment is still required.
1444	23639568	Permanent neonatal diabetes mellitus is a rare condition mostly due to heterozygous mutations in the KCNJ11, ABCC8 and INS genes.
1445	23639568	Mutations in PDX1, PTF1A, HNF1B, EIF2AK3, RFX6 and GATA6 genes have been shown to result in pancreatic agenesis or hypoplasia.
1446	23665564	Neuroendocrine-type K(ATP) channels, (SUR1/Kir6.2)4, couple the transmembrane flux of K(+), and thus membrane potential, with cellular metabolism in various cell types including insulin-secreting β-cells.
1447	23665564	A current regulatory model proposes that ATP hydrolysis is required to switch SUR1 into post-hydrolytic conformations able to antagonize the inhibitory action of nucleotide binding at the Kir6.2 pore, thus coupling enzymatic and channel activities.
1448	23665564	Neuroendocrine-type K(ATP) channels, (SUR1/Kir6.2)4, couple the transmembrane flux of K(+), and thus membrane potential, with cellular metabolism in various cell types including insulin-secreting β-cells.
1449	23665564	A current regulatory model proposes that ATP hydrolysis is required to switch SUR1 into post-hydrolytic conformations able to antagonize the inhibitory action of nucleotide binding at the Kir6.2 pore, thus coupling enzymatic and channel activities.
1450	23667671	Gain of channel function (GOF) mutations in the genes encoding Kir6.2 (KCNJ11) or the associated regulatory ssulfonylurea receptor 1 subunit (ABCC8), cause developmental delay, epilepsy and neonatal diabetes (DEND) due to suppressed cell excitability in pancreatic β-cells and neurons.
1451	23667671	The naturally occurring Kir6.2 mutation plus deletion (Ser225Thr, Pro226_Pro232del) as well as the isolated S225T mutation or isolated del226-232 deletion were coexpressed with SUR1 in COS cells in homozygous or heterozygous states.
1452	23667671	Gain of channel function (GOF) mutations in the genes encoding Kir6.2 (KCNJ11) or the associated regulatory ssulfonylurea receptor 1 subunit (ABCC8), cause developmental delay, epilepsy and neonatal diabetes (DEND) due to suppressed cell excitability in pancreatic β-cells and neurons.
1453	23667671	The naturally occurring Kir6.2 mutation plus deletion (Ser225Thr, Pro226_Pro232del) as well as the isolated S225T mutation or isolated del226-232 deletion were coexpressed with SUR1 in COS cells in homozygous or heterozygous states.
1454	23903354	Loss-of-function mutations in the KATP channel genes KCNJ11 and ABCC8 cause neonatal hyperinsulinism in humans.
1455	23959658	Although KCNJ11 mutations of the KATP channel within the β cell are known to prevent insulin secretion and cause permanent neonatal diabetes mellitus, the genotype-phenotype correlation continues to be of clinical interest.
1456	23961321	Highly replicated genes, for example TCF7L2, KCNQ1 and KCNJ11, are discussed in greater detail.
1457	23985558	Exposure to 25 mM glucose significantly reduced insulin content (p<0.05) and glucokinase activity (p<0.01) after 72 h.
1458	23985558	Effects of hyperglycemia on secretory function were accompanied by decreased mRNA expression of INS, GCK, PCSK1, PCSK2, PPP3CB, GJA1, ABCC8, and KCNJ11.
1459	23985558	Hyperglycemia-induced apoptosis was evident from increased activity of caspase 3/7 and decreased BCL2 protein.
1460	23991188	In contrast, hyperglycemic correction with insulin in diabetic rats normalized expression of brain Kir6.2, reduced ischemic brain damage and restored neuroprotective effects of sevoflurane post-conditioning.