Ignet

Gene Information

Gene symbol: PCSK2

Gene name: proprotein convertase subtilisin/kexin type 2

HGNC ID: 8744

Synonyms: PC2, SPC2

Related Genes

#	Gene Symbol	Number of hits
1	ABCC8	1 hits
2	APLP2	1 hits
3	AVP	1 hits
4	BRCA2	1 hits
5	CCKBR	1 hits
6	CDKN1A	1 hits
7	CDKN1B	1 hits
8	CDX2	1 hits
9	CPE	1 hits
10	ENPP1	1 hits
11	FABP2	1 hits
12	GCG	1 hits
13	GCK	1 hits
14	GCKR	1 hits
15	GHRL	1 hits
16	GIP	1 hits
17	GJA1	1 hits
18	GLP1R	1 hits
19	GPD2	1 hits
20	HK1	1 hits
21	HK2	1 hits
22	IAPP	1 hits
23	IL1B	1 hits
24	INS	1 hits
25	ISL1	1 hits
26	KCNJ11	1 hits
27	KCNJ3	1 hits
28	KCNJ6	1 hits
29	KLRG1	1 hits
30	LDLR	1 hits
31	NEUROD1	1 hits
32	NKX2-2	1 hits
33	PCSK1	1 hits
34	PCSK4	1 hits
35	PCSK5	1 hits
36	PCSK6	1 hits
37	PCSK7	1 hits
38	PDLIM5	1 hits
39	PDX1	1 hits
40	PFKL	1 hits
41	PKLR	1 hits
42	PKM2	1 hits
43	PPP1CB	1 hits
44	PPP1R3C	1 hits
45	PPP3CB	1 hits
46	PPP5C	1 hits
47	PSMD9	1 hits
48	SCG5	1 hits
49	SLC2A2	1 hits
50	SLC30A8	1 hits
51	SP1	1 hits
52	TCF7L2	1 hits

Related Sentences

#	PMID	Sentence
1	7698505	Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3.
2	7698505	PC2 is a type II proinsulin-processing enzyme, and it cleaves the proinsulin molecule on the COOH-terminal side of dibasic peptide, Lys64-Arg65, which joins the C-peptide and the A-chain domains.
3	7698505	Since non-insulin-dependent diabetes mellitus (NIDDM) is associated with increased secretion of proinsulin and proinsulin-like molecules, we conducted a case-control study to determine whether a genetic variation in PCSK2 might contribute to the development of NIDDM.
4	7698505	Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3.
5	7698505	PC2 is a type II proinsulin-processing enzyme, and it cleaves the proinsulin molecule on the COOH-terminal side of dibasic peptide, Lys64-Arg65, which joins the C-peptide and the A-chain domains.
6	7698505	Since non-insulin-dependent diabetes mellitus (NIDDM) is associated with increased secretion of proinsulin and proinsulin-like molecules, we conducted a case-control study to determine whether a genetic variation in PCSK2 might contribute to the development of NIDDM.
7	7698505	Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3.
8	7698505	PC2 is a type II proinsulin-processing enzyme, and it cleaves the proinsulin molecule on the COOH-terminal side of dibasic peptide, Lys64-Arg65, which joins the C-peptide and the A-chain domains.
9	7698505	Since non-insulin-dependent diabetes mellitus (NIDDM) is associated with increased secretion of proinsulin and proinsulin-like molecules, we conducted a case-control study to determine whether a genetic variation in PCSK2 might contribute to the development of NIDDM.
10	7983775	Prohormone Convertase 2 (PC2) is a specific endoprotease responsible for the processing of proinsulin to insulin.
11	7983775	The promoter region of the PC2 gene is very G + C rich and contains six potential Sp1 binding sites but no TATA or CAAT box.
12	7983775	Prohormone Convertase 2 (PC2) is a specific endoprotease responsible for the processing of proinsulin to insulin.
13	7983775	The promoter region of the PC2 gene is very G + C rich and contains six potential Sp1 binding sites but no TATA or CAAT box.
14	8440711	The biosynthesis of the subtilisin-related proprotein convertase PC3, but no that of the PC2 convertase, is regulated by glucose in parallel to proinsulin biosynthesis in rat pancreatic islets.
15	8440711	Proteolytic proinsulin processing is catalyzed by two endopeptidases putatively identified as the subtilisin-related PC2 and PC3 convertases (Bennett, D.
16	8440711	In this study, we demonstrate in isolated rat pancreatic islets that the biosynthesis of PC3 was specifically stimulated by glucose relatively parallel to that of proinsulin.
17	8440711	The stimulation of PC3 and proinsulin biosynthesis was observed above a threshold of 4 mM glucose and reached a maximum (about 7-10-fold) above 10 mM glucose concentrations.
18	8440711	Glucose stimulation for PC3 and proinsulin biosynthesis was rapid (occurring within 20 min and reaching a maximum by 60 min) and was not affected by the additional presence of actinomycin D, suggesting regulation predominantly at the translational level.
19	8440711	Moreover, the intracellular signals for glucose-stimulated PC3 and proinsulin biosynthesis appeared to be similar, requiring the metabolism of glucose.
20	8440711	PC3 has been implicated as the key endopeptidase in proinsulin to insulin conversion, in that it is the enzyme which preferentially initiates the process (Rhodes, C.
21	8440711	We suggest that co-ordinate stimulation of PC3 biosynthesis, along with that of its proinsulin substrate, elucidates an additional control point by which the mechanism of proprotein processing might be regulated.
22	8440711	The biosynthesis of the subtilisin-related proprotein convertase PC3, but no that of the PC2 convertase, is regulated by glucose in parallel to proinsulin biosynthesis in rat pancreatic islets.
23	8440711	Proteolytic proinsulin processing is catalyzed by two endopeptidases putatively identified as the subtilisin-related PC2 and PC3 convertases (Bennett, D.
24	8440711	In this study, we demonstrate in isolated rat pancreatic islets that the biosynthesis of PC3 was specifically stimulated by glucose relatively parallel to that of proinsulin.
25	8440711	The stimulation of PC3 and proinsulin biosynthesis was observed above a threshold of 4 mM glucose and reached a maximum (about 7-10-fold) above 10 mM glucose concentrations.
26	8440711	Glucose stimulation for PC3 and proinsulin biosynthesis was rapid (occurring within 20 min and reaching a maximum by 60 min) and was not affected by the additional presence of actinomycin D, suggesting regulation predominantly at the translational level.
27	8440711	Moreover, the intracellular signals for glucose-stimulated PC3 and proinsulin biosynthesis appeared to be similar, requiring the metabolism of glucose.
28	8440711	PC3 has been implicated as the key endopeptidase in proinsulin to insulin conversion, in that it is the enzyme which preferentially initiates the process (Rhodes, C.
29	8440711	We suggest that co-ordinate stimulation of PC3 biosynthesis, along with that of its proinsulin substrate, elucidates an additional control point by which the mechanism of proprotein processing might be regulated.
30	8557106	Processing of pro-islet amyloid polypeptide (proIAPP) by the prohormone convertase PC2.
31	8557106	Islet amyloid polypeptide (IAPP), 'amylin', is the component peptide of islet amyloid formed in Type 2 diabetes.
32	8557106	An in vitro translation/translocation system was used to separately examine processing of human proIAPP by the beta-cell endopeptidases PC2, PC3 or furin.
33	8557106	ProIAPP was converted to mature IAPP by PC2 but there was little conversion by furin or PC3.
34	8557106	Processing of pro-islet amyloid polypeptide (proIAPP) by the prohormone convertase PC2.
35	8557106	Islet amyloid polypeptide (IAPP), 'amylin', is the component peptide of islet amyloid formed in Type 2 diabetes.
36	8557106	An in vitro translation/translocation system was used to separately examine processing of human proIAPP by the beta-cell endopeptidases PC2, PC3 or furin.
37	8557106	ProIAPP was converted to mature IAPP by PC2 but there was little conversion by furin or PC3.
38	8557106	Processing of pro-islet amyloid polypeptide (proIAPP) by the prohormone convertase PC2.
39	8557106	Islet amyloid polypeptide (IAPP), 'amylin', is the component peptide of islet amyloid formed in Type 2 diabetes.
40	8557106	An in vitro translation/translocation system was used to separately examine processing of human proIAPP by the beta-cell endopeptidases PC2, PC3 or furin.
41	8557106	ProIAPP was converted to mature IAPP by PC2 but there was little conversion by furin or PC3.
42	8666140	Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3 (PC3).
43	8666140	PC3 is a type I proinsulin-processing enzyme that initiates the sequential processing of proinsulin to insulin by cleaving the proinsulin molecule on the COOH-terminal side of the dibasic peptide, Arg31-Arg32, joining the B-chain and C-peptide.
44	8666140	Thus, PC3 plays a key role in regulating insulin biosynthesis.
45	8666140	Expressions of insulin and PC3, but not PC2, are coordinately regulated by glucose, consistent with the important role of PC3 in regulating proinsulin processing.
46	8666140	NIDDM is associated with increased secretion of proinsulin and proinsulin-like molecules, suggesting that mutations in the PC3 gene may be involved in the development of this disorder.
47	8666140	The exon-intron organization of PC2 and PC3 genes are conserved, consistent with a common evolutionary origin for the prohormone convertase gene family.
48	8666140	Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3 (PC3).
49	8666140	PC3 is a type I proinsulin-processing enzyme that initiates the sequential processing of proinsulin to insulin by cleaving the proinsulin molecule on the COOH-terminal side of the dibasic peptide, Arg31-Arg32, joining the B-chain and C-peptide.
50	8666140	Thus, PC3 plays a key role in regulating insulin biosynthesis.
51	8666140	Expressions of insulin and PC3, but not PC2, are coordinately regulated by glucose, consistent with the important role of PC3 in regulating proinsulin processing.
52	8666140	NIDDM is associated with increased secretion of proinsulin and proinsulin-like molecules, suggesting that mutations in the PC3 gene may be involved in the development of this disorder.
53	8666140	The exon-intron organization of PC2 and PC3 genes are conserved, consistent with a common evolutionary origin for the prohormone convertase gene family.
54	8666140	Proinsulin is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3 (PC3).
55	8666140	PC3 is a type I proinsulin-processing enzyme that initiates the sequential processing of proinsulin to insulin by cleaving the proinsulin molecule on the COOH-terminal side of the dibasic peptide, Arg31-Arg32, joining the B-chain and C-peptide.
56	8666140	Thus, PC3 plays a key role in regulating insulin biosynthesis.
57	8666140	Expressions of insulin and PC3, but not PC2, are coordinately regulated by glucose, consistent with the important role of PC3 in regulating proinsulin processing.
58	8666140	NIDDM is associated with increased secretion of proinsulin and proinsulin-like molecules, suggesting that mutations in the PC3 gene may be involved in the development of this disorder.
59	8666140	The exon-intron organization of PC2 and PC3 genes are conserved, consistent with a common evolutionary origin for the prohormone convertase gene family.
60	9166665	This unusual peak was initially thought to represent partially processed insulin on the basis of its molecular size and susceptibility to trimming by carboxypeptidase B (CpB).
61	9166665	However, the findings of an active carboxypeptidase E (CpE) enzyme and the normal amidated forms of gastrin and cholecystokinin octapeptide (CCK-8) in Psammomys tissues were inconsistent with CpE-related aberrant processing of insulin.
62	9166665	The unusual structure of Psammomys insulin does not appear to contribute to the proinsulinemia observed in diabetic Psammomys since the HPLC-purified molecule did not inhibit PC1 and PC2 convertase activities in an in vitro assay.
63	9166680	Loci included the G-protein-coupled inwardly rectifying potassium channels expressed in beta-cells (KCNJ3 and KCNJ7), glucagon (GCG), glucokinase regulatory protein (GCKR), glucagon-like peptide I receptor (GLP1R), LIM/homeodomain islet-1 (ISL1), caudal-type homeodomain 3 (CDX3), proprotein convertase 2 (PCSK2), cholecystokinin B receptor (CCKBR), hexokinase 1 (HK1), hexokinase 2 (HK2), mitochondrial FAD-glycerophosphate dehydrogenase (GPD2), liver and muscle forms of pyruvate kinase (PKL, PKM), fatty acid-binding protein 2 (FABP2), hepatic phosphofructokinase (PFKL), protein serine/threonine phosphatase 1 beta (PPP1CB), and low-density lipoprotein receptor (LDLR).
64	9231654	We have previously reported that in the well-differentiated beta-cell line MIN6 cells, the beta-cell-specific differentiated characteristics, such as insulin content, expression of prohormone convertases PC2 and PC3, and glucose-regulated insulin secretion, diminished when the proprotein-processing endoprotease furin was highly expressed.
65	9662053	Insulin is synthesized in the pancreatic beta cell as a larger precursor molecule proinsulin which is converted to insulin and C-peptide by the concerted action of prohormone convertase 2 (PC2), prohormone convertase 3 (PC3) and carboxypeptidase E (CPE).
66	9814487	The vasopressin precursor is not processed in the hypothalamus of Wolfram syndrome patients with diabetes insipidus: evidence for the involvement of PC2 and 7B2.
67	9814487	Wolfram syndrome (WS) is characterized by optic atrophy, insulin-dependent diabetes mellitus, vasopressin (VP)-sensitive diabetes insipidus, and neurosensory hearing loss.
68	9814487	In addition, the proprotein convertase PC2 and the molecular chaperone 7B2 were absent.
69	9814487	As expression of PC2 and 7B2 was detected in the nearby nucleus basalis of Meynert of one WS patient and in the anterior lobe of the other WS patient, the absence of the two proteins in the paraventricular nucleus was not due to mutations in their genes.
70	9814487	The vasopressin precursor is not processed in the hypothalamus of Wolfram syndrome patients with diabetes insipidus: evidence for the involvement of PC2 and 7B2.
71	9814487	Wolfram syndrome (WS) is characterized by optic atrophy, insulin-dependent diabetes mellitus, vasopressin (VP)-sensitive diabetes insipidus, and neurosensory hearing loss.
72	9814487	In addition, the proprotein convertase PC2 and the molecular chaperone 7B2 were absent.
73	9814487	As expression of PC2 and 7B2 was detected in the nearby nucleus basalis of Meynert of one WS patient and in the anterior lobe of the other WS patient, the absence of the two proteins in the paraventricular nucleus was not due to mutations in their genes.
74	9814487	The vasopressin precursor is not processed in the hypothalamus of Wolfram syndrome patients with diabetes insipidus: evidence for the involvement of PC2 and 7B2.
75	9814487	Wolfram syndrome (WS) is characterized by optic atrophy, insulin-dependent diabetes mellitus, vasopressin (VP)-sensitive diabetes insipidus, and neurosensory hearing loss.
76	9814487	In addition, the proprotein convertase PC2 and the molecular chaperone 7B2 were absent.
77	9814487	As expression of PC2 and 7B2 was detected in the nearby nucleus basalis of Meynert of one WS patient and in the anterior lobe of the other WS patient, the absence of the two proteins in the paraventricular nucleus was not due to mutations in their genes.
78	10868954	After a 24-h culture with IL-1beta (30 U/ml), beta-cells exhibited a lower expression of the beta-cell-specific protein transcription factor pancreatic and duodenal homeobox gene (PDX)-1, glucose transporter GLUT2, and proinsulin convertase PC2, with a marked reduction (60-70%) in glucose-induced insulin production and selective sensitivity to the toxins alloxan (ALX) and streptozotocin (STZ).
79	10868954	On the other hand, the cells presented an increased expression of Mn-superoxide dismutase, heat shock protein 70, inducible heme oxygenase, and inducible nitrite oxide synthase.
80	10868954	Exposure to IL-1beta can thus protect beta-cells against conditions that cause necrosis; however, it did not protect against apoptosis induced by the additional presence of interferon-gamma or tumor necrosis factor-alpha.
81	10931181	Processing of synthetic pro-islet amyloid polypeptide (proIAPP) 'amylin' by recombinant prohormone convertase enzymes, PC2 and PC3, in vitro.
82	10931181	Islet amyloid polypeptide (IAPP), amylin, is the constituent peptide of pancreatic islet amyloid deposits which form in islets of Type 2 diabetic subjects.
83	10931181	To determine the enzymes responsible for proteolysis and their activity at the potential cleavage sites, synthetic human proIAPP was incubated (0.5-16 h) with recombinant prohormone convertases, PC2 or PC3 at appropriate conditions of calcium and pH.
84	10931181	PC3 was active initially at the N-terminal-IAPP junction and later at the C-terminus, whereas initial PC2 activity was at the IAPP-C-terminal junction.
85	10931181	There was no evidence for substantial competition for the processing enzymes when the combined substrates proinsulin and proIAPP were incubated with both PC2 and PC3.
86	10931181	As proinsulin cleavage is sequential in vivo (PC3 active at the B-chain-C-peptide junction, followed by PC2 at A chain-C-peptide junction), these data suggest that proteolysis of proIAPP and proinsulin is coincident in secretory granules and increased proinsulin secretion in diabetes could be accompanied by increased production of proIAPP.
87	10931181	Processing of synthetic pro-islet amyloid polypeptide (proIAPP) 'amylin' by recombinant prohormone convertase enzymes, PC2 and PC3, in vitro.
88	10931181	Islet amyloid polypeptide (IAPP), amylin, is the constituent peptide of pancreatic islet amyloid deposits which form in islets of Type 2 diabetic subjects.
89	10931181	To determine the enzymes responsible for proteolysis and their activity at the potential cleavage sites, synthetic human proIAPP was incubated (0.5-16 h) with recombinant prohormone convertases, PC2 or PC3 at appropriate conditions of calcium and pH.
90	10931181	PC3 was active initially at the N-terminal-IAPP junction and later at the C-terminus, whereas initial PC2 activity was at the IAPP-C-terminal junction.
91	10931181	There was no evidence for substantial competition for the processing enzymes when the combined substrates proinsulin and proIAPP were incubated with both PC2 and PC3.
92	10931181	As proinsulin cleavage is sequential in vivo (PC3 active at the B-chain-C-peptide junction, followed by PC2 at A chain-C-peptide junction), these data suggest that proteolysis of proIAPP and proinsulin is coincident in secretory granules and increased proinsulin secretion in diabetes could be accompanied by increased production of proIAPP.
93	10931181	Processing of synthetic pro-islet amyloid polypeptide (proIAPP) 'amylin' by recombinant prohormone convertase enzymes, PC2 and PC3, in vitro.
94	10931181	Islet amyloid polypeptide (IAPP), amylin, is the constituent peptide of pancreatic islet amyloid deposits which form in islets of Type 2 diabetic subjects.
95	10931181	To determine the enzymes responsible for proteolysis and their activity at the potential cleavage sites, synthetic human proIAPP was incubated (0.5-16 h) with recombinant prohormone convertases, PC2 or PC3 at appropriate conditions of calcium and pH.
96	10931181	PC3 was active initially at the N-terminal-IAPP junction and later at the C-terminus, whereas initial PC2 activity was at the IAPP-C-terminal junction.
97	10931181	There was no evidence for substantial competition for the processing enzymes when the combined substrates proinsulin and proIAPP were incubated with both PC2 and PC3.
98	10931181	As proinsulin cleavage is sequential in vivo (PC3 active at the B-chain-C-peptide junction, followed by PC2 at A chain-C-peptide junction), these data suggest that proteolysis of proIAPP and proinsulin is coincident in secretory granules and increased proinsulin secretion in diabetes could be accompanied by increased production of proIAPP.
99	10931181	Processing of synthetic pro-islet amyloid polypeptide (proIAPP) 'amylin' by recombinant prohormone convertase enzymes, PC2 and PC3, in vitro.
100	10931181	Islet amyloid polypeptide (IAPP), amylin, is the constituent peptide of pancreatic islet amyloid deposits which form in islets of Type 2 diabetic subjects.
101	10931181	To determine the enzymes responsible for proteolysis and their activity at the potential cleavage sites, synthetic human proIAPP was incubated (0.5-16 h) with recombinant prohormone convertases, PC2 or PC3 at appropriate conditions of calcium and pH.
102	10931181	PC3 was active initially at the N-terminal-IAPP junction and later at the C-terminus, whereas initial PC2 activity was at the IAPP-C-terminal junction.
103	10931181	There was no evidence for substantial competition for the processing enzymes when the combined substrates proinsulin and proIAPP were incubated with both PC2 and PC3.
104	10931181	As proinsulin cleavage is sequential in vivo (PC3 active at the B-chain-C-peptide junction, followed by PC2 at A chain-C-peptide junction), these data suggest that proteolysis of proIAPP and proinsulin is coincident in secretory granules and increased proinsulin secretion in diabetes could be accompanied by increased production of proIAPP.
105	10931181	Processing of synthetic pro-islet amyloid polypeptide (proIAPP) 'amylin' by recombinant prohormone convertase enzymes, PC2 and PC3, in vitro.
106	10931181	Islet amyloid polypeptide (IAPP), amylin, is the constituent peptide of pancreatic islet amyloid deposits which form in islets of Type 2 diabetic subjects.
107	10931181	To determine the enzymes responsible for proteolysis and their activity at the potential cleavage sites, synthetic human proIAPP was incubated (0.5-16 h) with recombinant prohormone convertases, PC2 or PC3 at appropriate conditions of calcium and pH.
108	10931181	PC3 was active initially at the N-terminal-IAPP junction and later at the C-terminus, whereas initial PC2 activity was at the IAPP-C-terminal junction.
109	10931181	There was no evidence for substantial competition for the processing enzymes when the combined substrates proinsulin and proIAPP were incubated with both PC2 and PC3.
110	10931181	As proinsulin cleavage is sequential in vivo (PC3 active at the B-chain-C-peptide junction, followed by PC2 at A chain-C-peptide junction), these data suggest that proteolysis of proIAPP and proinsulin is coincident in secretory granules and increased proinsulin secretion in diabetes could be accompanied by increased production of proIAPP.
111	11246872	The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site.
112	11246872	Impaired processing of pro-islet amyloid polypeptide (proIAPP), the precursor of the beta-cell peptide islet amyloid polypeptide (IAPP) (amylin), has been implicated in islet amyloid formation in type 2 diabetes.
113	11246872	The prohormone convertase enzymes PC3 (also known as PC1) and PC2 are localized to beta-cell secretory granules with proIAPP and proinsulin and are responsible for proinsulin processing.
114	11246872	These data indicate that PC2 is essential for processing of proIAPP at the NH2-terminal cleavage site in vivo and that PC3 is likely only capable of processing proIAPP at the COOH-terminal cleavage site.
115	11246872	The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site.
116	11246872	Impaired processing of pro-islet amyloid polypeptide (proIAPP), the precursor of the beta-cell peptide islet amyloid polypeptide (IAPP) (amylin), has been implicated in islet amyloid formation in type 2 diabetes.
117	11246872	The prohormone convertase enzymes PC3 (also known as PC1) and PC2 are localized to beta-cell secretory granules with proIAPP and proinsulin and are responsible for proinsulin processing.
118	11246872	These data indicate that PC2 is essential for processing of proIAPP at the NH2-terminal cleavage site in vivo and that PC3 is likely only capable of processing proIAPP at the COOH-terminal cleavage site.
119	11246872	The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site.
120	11246872	Impaired processing of pro-islet amyloid polypeptide (proIAPP), the precursor of the beta-cell peptide islet amyloid polypeptide (IAPP) (amylin), has been implicated in islet amyloid formation in type 2 diabetes.
121	11246872	The prohormone convertase enzymes PC3 (also known as PC1) and PC2 are localized to beta-cell secretory granules with proIAPP and proinsulin and are responsible for proinsulin processing.
122	11246872	These data indicate that PC2 is essential for processing of proIAPP at the NH2-terminal cleavage site in vivo and that PC3 is likely only capable of processing proIAPP at the COOH-terminal cleavage site.
123	11733865	Interleukin-1 beta inhibits proinsulin conversion in rat beta-cells via a nitric oxide-dependent pathway.
124	11733865	Exposure of pancreatic beta-cells to interleukin-1 beta (IL-1 beta) alters their protein expression and phenotype.
125	11733865	Previous work has shown that IL-1 beta inhibited proinsulin conversion in rat islets, but the mechanism of this inhibition remained unknown.
126	11733865	To investigate this phenomenon further, we examined purified rat beta-cells for IL-1 beta-induced inhibition of proinsulin conversion and nitric oxide (NO)-dependency of this inhibitory process.
127	11733865	Rat beta-cells were cultured for 24 h with or without IL-1 beta and the inducible-nitric-oxide-synthase (iNOS) inhibitor N(G)-methyl-L-arginine (NMA).
128	11733865	Exposure to IL-1 beta suppressed proinsulin-1 and proinsulin-2 synthesis by more than 50 %.
129	11733865	The suppressive effects of IL-1 beta on proinsulin synthesis and conversion were prevented by addition of NMA.
130	11733865	Exposure to IL-1 beta also decreased the expression of the proinsulin convertase (PC) PC2.
131	11733865	In conclusion, IL-1 beta inhibition of proinsulin conversion in rat beta-cells occurs via an NO-mediated pathway.
132	11812747	These results demonstrate that the lack of mature glucagon in PC2(-/-) mice is responsible for the aberrant blood glucose levels, islet morphology, and gene expression, and they confirm the role of glucagon as a tonic insulin antagonist in regulating glycemia.
133	12193559	Glucagon-like peptide-1 (GLP-1) is a potent stimulator of glucose-dependent insulin secretion.
134	12193559	To examine the requirements for proEx-4 processing in mammalian cells, BHK fibroblasts, InR1-G9 islet A cells, and AtT-20 corticotropes, which express different prohormone convertases (furin, prohormone convertase 2, and prohormone convertase 1, respectively) were transfected with full-length lizard proEx-4, and the processing of proexendin was examined by HPLC and RIA (n = 3).
135	12952363	Using reverse transcriptase-polymerase chain reaction, no differences in mRNA expression levels were found for insulin, islet amyloid polypeptide (IAPP), and the prohormone convertase (PC) 1 and PC2 between 6-week-old untreated ZDF rats and 19-week-old sham- and phlorizin-treated ZDF rats.
136	14693708	Role of beta-cell prohormone convertase (PC)1/3 in processing of pro-islet amyloid polypeptide.
137	14693708	Islet amyloid polypeptide (IAPP) (amylin), the major component of islet amyloid, is produced by cleavage at the COOH- and NH(2)-termini of its precursor, proIAPP, likely by the beta-cell prohormone convertases (PC) 1/3 and PC2.
138	14693708	Mice lacking PC2 can process proIAPP at its COOH- but not its NH(2)-terminal cleavage site, suggesting that PC1/3 is capable of initiating proIAPP cleavage at its COOH-terminus.
139	14693708	Next, GH3 cells that do not normally express proIAPP or detectable levels of PC1/3 or PC2 were cotransduced with adenoviruses expressing rat proIAPP and either PC2 or PC1/3.
140	14693708	Coexpression of proIAPP and PC2 resulted in production of mature IAPP, whereas in cells that coexpressed proIAPP and PC1/3 only a 6-kDa intermediate was produced.
141	14693708	We conclude that PC1/3 is important for processing of proIAPP at the COOH-terminus, but in its absence, PC2 can initiate complete processing of proIAPP to IAPP by cleaving the precursor at either its NH(2)- or COOH-terminal cleavage sites.
142	14693708	Role of beta-cell prohormone convertase (PC)1/3 in processing of pro-islet amyloid polypeptide.
143	14693708	Islet amyloid polypeptide (IAPP) (amylin), the major component of islet amyloid, is produced by cleavage at the COOH- and NH(2)-termini of its precursor, proIAPP, likely by the beta-cell prohormone convertases (PC) 1/3 and PC2.
144	14693708	Mice lacking PC2 can process proIAPP at its COOH- but not its NH(2)-terminal cleavage site, suggesting that PC1/3 is capable of initiating proIAPP cleavage at its COOH-terminus.
145	14693708	Next, GH3 cells that do not normally express proIAPP or detectable levels of PC1/3 or PC2 were cotransduced with adenoviruses expressing rat proIAPP and either PC2 or PC1/3.
146	14693708	Coexpression of proIAPP and PC2 resulted in production of mature IAPP, whereas in cells that coexpressed proIAPP and PC1/3 only a 6-kDa intermediate was produced.
147	14693708	We conclude that PC1/3 is important for processing of proIAPP at the COOH-terminus, but in its absence, PC2 can initiate complete processing of proIAPP to IAPP by cleaving the precursor at either its NH(2)- or COOH-terminal cleavage sites.
148	14693708	Role of beta-cell prohormone convertase (PC)1/3 in processing of pro-islet amyloid polypeptide.
149	14693708	Islet amyloid polypeptide (IAPP) (amylin), the major component of islet amyloid, is produced by cleavage at the COOH- and NH(2)-termini of its precursor, proIAPP, likely by the beta-cell prohormone convertases (PC) 1/3 and PC2.
150	14693708	Mice lacking PC2 can process proIAPP at its COOH- but not its NH(2)-terminal cleavage site, suggesting that PC1/3 is capable of initiating proIAPP cleavage at its COOH-terminus.
151	14693708	Next, GH3 cells that do not normally express proIAPP or detectable levels of PC1/3 or PC2 were cotransduced with adenoviruses expressing rat proIAPP and either PC2 or PC1/3.
152	14693708	Coexpression of proIAPP and PC2 resulted in production of mature IAPP, whereas in cells that coexpressed proIAPP and PC1/3 only a 6-kDa intermediate was produced.
153	14693708	We conclude that PC1/3 is important for processing of proIAPP at the COOH-terminus, but in its absence, PC2 can initiate complete processing of proIAPP to IAPP by cleaving the precursor at either its NH(2)- or COOH-terminal cleavage sites.
154	14693708	Role of beta-cell prohormone convertase (PC)1/3 in processing of pro-islet amyloid polypeptide.
155	14693708	Islet amyloid polypeptide (IAPP) (amylin), the major component of islet amyloid, is produced by cleavage at the COOH- and NH(2)-termini of its precursor, proIAPP, likely by the beta-cell prohormone convertases (PC) 1/3 and PC2.
156	14693708	Mice lacking PC2 can process proIAPP at its COOH- but not its NH(2)-terminal cleavage site, suggesting that PC1/3 is capable of initiating proIAPP cleavage at its COOH-terminus.
157	14693708	Next, GH3 cells that do not normally express proIAPP or detectable levels of PC1/3 or PC2 were cotransduced with adenoviruses expressing rat proIAPP and either PC2 or PC1/3.
158	14693708	Coexpression of proIAPP and PC2 resulted in production of mature IAPP, whereas in cells that coexpressed proIAPP and PC1/3 only a 6-kDa intermediate was produced.
159	14693708	We conclude that PC1/3 is important for processing of proIAPP at the COOH-terminus, but in its absence, PC2 can initiate complete processing of proIAPP to IAPP by cleaving the precursor at either its NH(2)- or COOH-terminal cleavage sites.
160	14693708	Role of beta-cell prohormone convertase (PC)1/3 in processing of pro-islet amyloid polypeptide.
161	14693708	Islet amyloid polypeptide (IAPP) (amylin), the major component of islet amyloid, is produced by cleavage at the COOH- and NH(2)-termini of its precursor, proIAPP, likely by the beta-cell prohormone convertases (PC) 1/3 and PC2.
162	14693708	Mice lacking PC2 can process proIAPP at its COOH- but not its NH(2)-terminal cleavage site, suggesting that PC1/3 is capable of initiating proIAPP cleavage at its COOH-terminus.
163	14693708	Next, GH3 cells that do not normally express proIAPP or detectable levels of PC1/3 or PC2 were cotransduced with adenoviruses expressing rat proIAPP and either PC2 or PC1/3.
164	14693708	Coexpression of proIAPP and PC2 resulted in production of mature IAPP, whereas in cells that coexpressed proIAPP and PC1/3 only a 6-kDa intermediate was produced.
165	14693708	We conclude that PC1/3 is important for processing of proIAPP at the COOH-terminus, but in its absence, PC2 can initiate complete processing of proIAPP to IAPP by cleaving the precursor at either its NH(2)- or COOH-terminal cleavage sites.
166	15802374	Processing of pro-islet amyloid polypeptide in the constitutive and regulated secretory pathways of beta cells.
167	15802374	Islet amyloid is a pathologic characteristic of the pancreas in type 2 diabetes comprised mainly of the beta-cell peptide islet amyloid polypeptide (IAPP; amylin).
168	15802374	We conclude that normal processing of proIAPP is a two-step process initiated by cleavage at its COOH terminus (likely by prohormone convertase 1/3 in the TGN) followed by cleavage at its NH2 terminus (by prohormone convertase 2 in granules) to form IAPP.
169	15983213	The amyloid present in the islets of Langerhans in type 2 diabetes is polymerized islet amyloid polypeptide (IAPP).
170	15983213	This step is performed by the prohormone convertases PC2 and PC1/3.
171	15983213	PC2 processes proIAPP preferably at the NH2-terminal processing site, and PC1/3 processes proIAPP exclusively at the COOH-terminal site.
172	15983213	Additionally, h-proIAPP was transfected into three different pituitary-derived cell lines with different prohormone convertase profiles: AtT-20 cells (deficient in PC2), GH3 cells (deficient in PC1/3), and GH4C1 cells (deficient in both convertases).
173	15983213	The amyloid present in the islets of Langerhans in type 2 diabetes is polymerized islet amyloid polypeptide (IAPP).
174	15983213	This step is performed by the prohormone convertases PC2 and PC1/3.
175	15983213	PC2 processes proIAPP preferably at the NH2-terminal processing site, and PC1/3 processes proIAPP exclusively at the COOH-terminal site.
176	15983213	Additionally, h-proIAPP was transfected into three different pituitary-derived cell lines with different prohormone convertase profiles: AtT-20 cells (deficient in PC2), GH3 cells (deficient in PC1/3), and GH4C1 cells (deficient in both convertases).
177	15983213	The amyloid present in the islets of Langerhans in type 2 diabetes is polymerized islet amyloid polypeptide (IAPP).
178	15983213	This step is performed by the prohormone convertases PC2 and PC1/3.
179	15983213	PC2 processes proIAPP preferably at the NH2-terminal processing site, and PC1/3 processes proIAPP exclusively at the COOH-terminal site.
180	15983213	Additionally, h-proIAPP was transfected into three different pituitary-derived cell lines with different prohormone convertase profiles: AtT-20 cells (deficient in PC2), GH3 cells (deficient in PC1/3), and GH4C1 cells (deficient in both convertases).
181	16476726	Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor.
182	16476726	The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest.
183	16476726	Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage of intestinal proglucagon, resulting in formation of GLP-1, as demonstrated in PC1/3-deficient mice.
184	16476726	This study investigates the processing of proGIP in PC1/3 and PC2 null mice and in cell lines using adenovirus-mediated overexpression.
185	16476726	Supporting a role for PC1/3 in proGIP processing, we found co-localization of GIP and PC1/3 but not PC2 in intestinal sections by immunohistochemistry, and analysis of intestinal extracts from PC1/3-deficient animals demonstrated severely impaired processing to GIP, whereas processing to GIP was unaltered in PC2-deficient mice.
186	16476726	Accordingly, overexpression of preproGIP in the neuroendocrine AtT-20 cell line that expresses high levels of endogenous PC1/3 and negligible levels of PC2 resulted in production of GIP.
187	16476726	Similar results were obtained after co-expression of preproGIP and PC1/3 in GH4 cells that express no PC2 and only low levels of PC1/3.
188	16476726	In addition, studies in GH4 cells and the alpha-TC1.9 cell line, expressing PC2 but not PC1/3, indicate that PC2 can mediate processing to GIP but also to other fragments not found in intestinal extracts.
189	16476726	Taken together, our data indicate that PC1/3 is essential and sufficient for the production of the intestinal incretin hormone GIP, whereas PC2, although capable of cleaving proGIP, does not participate in intestinal proGIP processing and is not found in intestinal GIP-expressing cells.
190	16476726	Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor.
191	16476726	The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest.
192	16476726	Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage of intestinal proglucagon, resulting in formation of GLP-1, as demonstrated in PC1/3-deficient mice.
193	16476726	This study investigates the processing of proGIP in PC1/3 and PC2 null mice and in cell lines using adenovirus-mediated overexpression.
194	16476726	Supporting a role for PC1/3 in proGIP processing, we found co-localization of GIP and PC1/3 but not PC2 in intestinal sections by immunohistochemistry, and analysis of intestinal extracts from PC1/3-deficient animals demonstrated severely impaired processing to GIP, whereas processing to GIP was unaltered in PC2-deficient mice.
195	16476726	Accordingly, overexpression of preproGIP in the neuroendocrine AtT-20 cell line that expresses high levels of endogenous PC1/3 and negligible levels of PC2 resulted in production of GIP.
196	16476726	Similar results were obtained after co-expression of preproGIP and PC1/3 in GH4 cells that express no PC2 and only low levels of PC1/3.
197	16476726	In addition, studies in GH4 cells and the alpha-TC1.9 cell line, expressing PC2 but not PC1/3, indicate that PC2 can mediate processing to GIP but also to other fragments not found in intestinal extracts.
198	16476726	Taken together, our data indicate that PC1/3 is essential and sufficient for the production of the intestinal incretin hormone GIP, whereas PC2, although capable of cleaving proGIP, does not participate in intestinal proGIP processing and is not found in intestinal GIP-expressing cells.
199	16476726	Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor.
200	16476726	The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest.
201	16476726	Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage of intestinal proglucagon, resulting in formation of GLP-1, as demonstrated in PC1/3-deficient mice.
202	16476726	This study investigates the processing of proGIP in PC1/3 and PC2 null mice and in cell lines using adenovirus-mediated overexpression.
203	16476726	Supporting a role for PC1/3 in proGIP processing, we found co-localization of GIP and PC1/3 but not PC2 in intestinal sections by immunohistochemistry, and analysis of intestinal extracts from PC1/3-deficient animals demonstrated severely impaired processing to GIP, whereas processing to GIP was unaltered in PC2-deficient mice.
204	16476726	Accordingly, overexpression of preproGIP in the neuroendocrine AtT-20 cell line that expresses high levels of endogenous PC1/3 and negligible levels of PC2 resulted in production of GIP.
205	16476726	Similar results were obtained after co-expression of preproGIP and PC1/3 in GH4 cells that express no PC2 and only low levels of PC1/3.
206	16476726	In addition, studies in GH4 cells and the alpha-TC1.9 cell line, expressing PC2 but not PC1/3, indicate that PC2 can mediate processing to GIP but also to other fragments not found in intestinal extracts.
207	16476726	Taken together, our data indicate that PC1/3 is essential and sufficient for the production of the intestinal incretin hormone GIP, whereas PC2, although capable of cleaving proGIP, does not participate in intestinal proGIP processing and is not found in intestinal GIP-expressing cells.
208	16476726	Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor.
209	16476726	The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest.
210	16476726	Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage of intestinal proglucagon, resulting in formation of GLP-1, as demonstrated in PC1/3-deficient mice.
211	16476726	This study investigates the processing of proGIP in PC1/3 and PC2 null mice and in cell lines using adenovirus-mediated overexpression.
212	16476726	Supporting a role for PC1/3 in proGIP processing, we found co-localization of GIP and PC1/3 but not PC2 in intestinal sections by immunohistochemistry, and analysis of intestinal extracts from PC1/3-deficient animals demonstrated severely impaired processing to GIP, whereas processing to GIP was unaltered in PC2-deficient mice.
213	16476726	Accordingly, overexpression of preproGIP in the neuroendocrine AtT-20 cell line that expresses high levels of endogenous PC1/3 and negligible levels of PC2 resulted in production of GIP.
214	16476726	Similar results were obtained after co-expression of preproGIP and PC1/3 in GH4 cells that express no PC2 and only low levels of PC1/3.
215	16476726	In addition, studies in GH4 cells and the alpha-TC1.9 cell line, expressing PC2 but not PC1/3, indicate that PC2 can mediate processing to GIP but also to other fragments not found in intestinal extracts.
216	16476726	Taken together, our data indicate that PC1/3 is essential and sufficient for the production of the intestinal incretin hormone GIP, whereas PC2, although capable of cleaving proGIP, does not participate in intestinal proGIP processing and is not found in intestinal GIP-expressing cells.
217	16476726	Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor.
218	16476726	The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest.
219	16476726	Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage of intestinal proglucagon, resulting in formation of GLP-1, as demonstrated in PC1/3-deficient mice.
220	16476726	This study investigates the processing of proGIP in PC1/3 and PC2 null mice and in cell lines using adenovirus-mediated overexpression.
221	16476726	Supporting a role for PC1/3 in proGIP processing, we found co-localization of GIP and PC1/3 but not PC2 in intestinal sections by immunohistochemistry, and analysis of intestinal extracts from PC1/3-deficient animals demonstrated severely impaired processing to GIP, whereas processing to GIP was unaltered in PC2-deficient mice.
222	16476726	Accordingly, overexpression of preproGIP in the neuroendocrine AtT-20 cell line that expresses high levels of endogenous PC1/3 and negligible levels of PC2 resulted in production of GIP.
223	16476726	Similar results were obtained after co-expression of preproGIP and PC1/3 in GH4 cells that express no PC2 and only low levels of PC1/3.
224	16476726	In addition, studies in GH4 cells and the alpha-TC1.9 cell line, expressing PC2 but not PC1/3, indicate that PC2 can mediate processing to GIP but also to other fragments not found in intestinal extracts.
225	16476726	Taken together, our data indicate that PC1/3 is essential and sufficient for the production of the intestinal incretin hormone GIP, whereas PC2, although capable of cleaving proGIP, does not participate in intestinal proGIP processing and is not found in intestinal GIP-expressing cells.
226	16476726	Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor.
227	16476726	The physiology of the incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and their role in type 2 diabetes currently attract great interest.
228	16476726	Recently we reported an essential role for prohormone convertase (PC) 1/3 in the cleavage of intestinal proglucagon, resulting in formation of GLP-1, as demonstrated in PC1/3-deficient mice.
229	16476726	This study investigates the processing of proGIP in PC1/3 and PC2 null mice and in cell lines using adenovirus-mediated overexpression.
230	16476726	Supporting a role for PC1/3 in proGIP processing, we found co-localization of GIP and PC1/3 but not PC2 in intestinal sections by immunohistochemistry, and analysis of intestinal extracts from PC1/3-deficient animals demonstrated severely impaired processing to GIP, whereas processing to GIP was unaltered in PC2-deficient mice.
231	16476726	Accordingly, overexpression of preproGIP in the neuroendocrine AtT-20 cell line that expresses high levels of endogenous PC1/3 and negligible levels of PC2 resulted in production of GIP.
232	16476726	Similar results were obtained after co-expression of preproGIP and PC1/3 in GH4 cells that express no PC2 and only low levels of PC1/3.
233	16476726	In addition, studies in GH4 cells and the alpha-TC1.9 cell line, expressing PC2 but not PC1/3, indicate that PC2 can mediate processing to GIP but also to other fragments not found in intestinal extracts.
234	16476726	Taken together, our data indicate that PC1/3 is essential and sufficient for the production of the intestinal incretin hormone GIP, whereas PC2, although capable of cleaving proGIP, does not participate in intestinal proGIP processing and is not found in intestinal GIP-expressing cells.
235	16866369	Characterization of the heparin binding site in the N-terminus of human pro-islet amyloid polypeptide: implications for amyloid formation.
236	16866369	Islet amyloid polypeptide (IAPP), also referred to as amylin, aggregates in the islet extracellular space to form amyloid deposits in up to 95% of patients with the disease.
237	16866369	IAPP is stored with insulin in beta-islet cells and is processed in parallel by subtilisin-like prohormone convertases prior to secretion.
238	16866369	Immunohistochemical studies implicate the presence of the heparan sulfate proteoglycan (HSPG) perlecan in islet amyloid deposits, suggesting a role for HSPGs in mediating amyloid deposition in type 2 diabetes and implicating a binding domain in the N-terminus of proIAPP.
239	16873681	Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death.
240	16873681	Islet amyloid, formed by aggregation of islet amyloid polypeptide (IAPP; amylin), is a pathological characteristic of the pancreas in type 2 diabetes and may contribute to the progressive loss of beta-cells in this disease.
241	16873681	GH3 cells lacking the prohormone convertase 1/3 (PC1/3) and IAPP and with very low levels of prohormone convertase 2 (PC2) were transduced with adenovirus (Ad) expressing human or rat (control) proIAPP linked to green fluorescent protein, with or without Ad-PC2 or Ad-PC1/3.
242	16873681	COOH-terminal processing of human proIAPP by PC1/3 increased (hIAPP+PC1/3 10.4 +/- 0.7%; P < 0.05), whereas NH(2)-terminal processing of proIAPP by addition of PC2 markedly decreased (hIAPP+PC2 5.5 +/- 0.5%; P < 0.05) the number of apoptotic GH3 cells.
243	16873681	Islets from mice lacking PC2 and with beta-cell expression of human proIAPP (hIAPP(+/+)/PC2(-/-)) developed amyloid associated with beta-cell death during 2-week culture.
244	16873681	Rescue of PC2 expression by ex vivo transduction with Ad-PC2 restored NH(2)-terminal processing to mature IAPP and decreased both the extent of amyloid formation and the number of TUNEL-positive cells (-PC2 26.5 +/- 4.1% vs.
245	16873681	Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death.
246	16873681	Islet amyloid, formed by aggregation of islet amyloid polypeptide (IAPP; amylin), is a pathological characteristic of the pancreas in type 2 diabetes and may contribute to the progressive loss of beta-cells in this disease.
247	16873681	GH3 cells lacking the prohormone convertase 1/3 (PC1/3) and IAPP and with very low levels of prohormone convertase 2 (PC2) were transduced with adenovirus (Ad) expressing human or rat (control) proIAPP linked to green fluorescent protein, with or without Ad-PC2 or Ad-PC1/3.
248	16873681	COOH-terminal processing of human proIAPP by PC1/3 increased (hIAPP+PC1/3 10.4 +/- 0.7%; P < 0.05), whereas NH(2)-terminal processing of proIAPP by addition of PC2 markedly decreased (hIAPP+PC2 5.5 +/- 0.5%; P < 0.05) the number of apoptotic GH3 cells.
249	16873681	Islets from mice lacking PC2 and with beta-cell expression of human proIAPP (hIAPP(+/+)/PC2(-/-)) developed amyloid associated with beta-cell death during 2-week culture.
250	16873681	Rescue of PC2 expression by ex vivo transduction with Ad-PC2 restored NH(2)-terminal processing to mature IAPP and decreased both the extent of amyloid formation and the number of TUNEL-positive cells (-PC2 26.5 +/- 4.1% vs.
251	16873681	Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death.
252	16873681	Islet amyloid, formed by aggregation of islet amyloid polypeptide (IAPP; amylin), is a pathological characteristic of the pancreas in type 2 diabetes and may contribute to the progressive loss of beta-cells in this disease.
253	16873681	GH3 cells lacking the prohormone convertase 1/3 (PC1/3) and IAPP and with very low levels of prohormone convertase 2 (PC2) were transduced with adenovirus (Ad) expressing human or rat (control) proIAPP linked to green fluorescent protein, with or without Ad-PC2 or Ad-PC1/3.
254	16873681	COOH-terminal processing of human proIAPP by PC1/3 increased (hIAPP+PC1/3 10.4 +/- 0.7%; P < 0.05), whereas NH(2)-terminal processing of proIAPP by addition of PC2 markedly decreased (hIAPP+PC2 5.5 +/- 0.5%; P < 0.05) the number of apoptotic GH3 cells.
255	16873681	Islets from mice lacking PC2 and with beta-cell expression of human proIAPP (hIAPP(+/+)/PC2(-/-)) developed amyloid associated with beta-cell death during 2-week culture.
256	16873681	Rescue of PC2 expression by ex vivo transduction with Ad-PC2 restored NH(2)-terminal processing to mature IAPP and decreased both the extent of amyloid formation and the number of TUNEL-positive cells (-PC2 26.5 +/- 4.1% vs.
257	16873681	Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death.
258	16873681	Islet amyloid, formed by aggregation of islet amyloid polypeptide (IAPP; amylin), is a pathological characteristic of the pancreas in type 2 diabetes and may contribute to the progressive loss of beta-cells in this disease.
259	16873681	GH3 cells lacking the prohormone convertase 1/3 (PC1/3) and IAPP and with very low levels of prohormone convertase 2 (PC2) were transduced with adenovirus (Ad) expressing human or rat (control) proIAPP linked to green fluorescent protein, with or without Ad-PC2 or Ad-PC1/3.
260	16873681	COOH-terminal processing of human proIAPP by PC1/3 increased (hIAPP+PC1/3 10.4 +/- 0.7%; P < 0.05), whereas NH(2)-terminal processing of proIAPP by addition of PC2 markedly decreased (hIAPP+PC2 5.5 +/- 0.5%; P < 0.05) the number of apoptotic GH3 cells.
261	16873681	Islets from mice lacking PC2 and with beta-cell expression of human proIAPP (hIAPP(+/+)/PC2(-/-)) developed amyloid associated with beta-cell death during 2-week culture.
262	16873681	Rescue of PC2 expression by ex vivo transduction with Ad-PC2 restored NH(2)-terminal processing to mature IAPP and decreased both the extent of amyloid formation and the number of TUNEL-positive cells (-PC2 26.5 +/- 4.1% vs.
263	16873681	Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death.
264	16873681	Islet amyloid, formed by aggregation of islet amyloid polypeptide (IAPP; amylin), is a pathological characteristic of the pancreas in type 2 diabetes and may contribute to the progressive loss of beta-cells in this disease.
265	16873681	GH3 cells lacking the prohormone convertase 1/3 (PC1/3) and IAPP and with very low levels of prohormone convertase 2 (PC2) were transduced with adenovirus (Ad) expressing human or rat (control) proIAPP linked to green fluorescent protein, with or without Ad-PC2 or Ad-PC1/3.
266	16873681	COOH-terminal processing of human proIAPP by PC1/3 increased (hIAPP+PC1/3 10.4 +/- 0.7%; P < 0.05), whereas NH(2)-terminal processing of proIAPP by addition of PC2 markedly decreased (hIAPP+PC2 5.5 +/- 0.5%; P < 0.05) the number of apoptotic GH3 cells.
267	16873681	Islets from mice lacking PC2 and with beta-cell expression of human proIAPP (hIAPP(+/+)/PC2(-/-)) developed amyloid associated with beta-cell death during 2-week culture.
268	16873681	Rescue of PC2 expression by ex vivo transduction with Ad-PC2 restored NH(2)-terminal processing to mature IAPP and decreased both the extent of amyloid formation and the number of TUNEL-positive cells (-PC2 26.5 +/- 4.1% vs.
269	16938896	Glucagon-like peptide 1 (GLP-1) is a hormone that has received significant attention as a therapy for diabetes because of its ability to stimulate insulin biosynthesis and release and to promote growth and survival of insulin-producing beta cells.
270	16938896	While GLP-1 is produced from the proglucagon precursor by means of prohormone convertase (PC) 1/3 activity in enteroendocrine L cells, the same precursor is differentially processed by PC2 in pancreatic islet alpha cells to release glucagon, leaving GLP-1 trapped within a larger fragment with no known function.
271	16938896	We hypothesized that we could induce GLP-1 production directly within pancreatic islets by means of delivery of PC1/3 and, further, that this intervention would improve the viability and function of islets.
272	16938896	Here, we show that adenovirus-mediated expression of PC1/3 in alpha cells increases islet GLP-1 secretion, resulting in improved glucose-stimulated insulin secretion and enhanced survival in response to cytokine treatment.
273	16938896	PC1/3 expression in alpha cells also improved performance after islet transplantation in a mouse model of type 1 diabetes, possibly by enhancing nuclear Pdx1 and insulin content of islet beta cells.
274	17012247	Proteolysis occurring at basic residues is mediated by the basic amino acid-specific proprotein convertases, namely: PC1/3, PC2, furin, PACE4, PC4, PC5/6, and PC7.
275	17012247	In contrast, proteolysis at nonbasic residues is performed by the subtilisin/kexin-like isozyme-1 (SKI-1/S1P) and the newly identified neural apoptosis-regulated convertase-1 (PCSK9/NARC-1).
276	18784614	The processing of preproghrelin in the stomach by prohormone convertase (PC) 1/3 produces ghrelin and possibly obestatin.
277	18784614	When preproghrelin cells were immunoreactive for ghrelin, they were also immunoreactive for obestatin and PC1/3.
278	18784614	None of the ghrelin positive cells stained for insulin, but we observed ghrelin positive/glucagon negative and ghrelin positive/glucagon positive cells.
279	18784614	Ghrelin positive cells contained PC1/3 or PC2.
280	18784614	In summary, in stomach, an excess of preproghrelin positive cells compared with ghrelin/PC1/3 positive cells suggests that PC1/3 determines preproghrelin processing to ghrelin.
281	18784614	In pancreas, the colocalization of PC1/3 or PC2 in ghrelin positive cells points to a role for both PCs in preproghrelin processing.
282	18784614	The processing of preproghrelin in the stomach by prohormone convertase (PC) 1/3 produces ghrelin and possibly obestatin.
283	18784614	When preproghrelin cells were immunoreactive for ghrelin, they were also immunoreactive for obestatin and PC1/3.
284	18784614	None of the ghrelin positive cells stained for insulin, but we observed ghrelin positive/glucagon negative and ghrelin positive/glucagon positive cells.
285	18784614	Ghrelin positive cells contained PC1/3 or PC2.
286	18784614	In summary, in stomach, an excess of preproghrelin positive cells compared with ghrelin/PC1/3 positive cells suggests that PC1/3 determines preproghrelin processing to ghrelin.
287	18784614	In pancreas, the colocalization of PC1/3 or PC2 in ghrelin positive cells points to a role for both PCs in preproghrelin processing.
288	18941442	Transplantation of PC1/3-Expressing alpha-cells improves glucose handling and cold tolerance in leptin-resistant mice.
289	18941442	Glucagon-like peptide-1 (GLP-1) has received much attention as a new treatment for diabetes because of its multiple blood glucose-lowering effects, including glucose-dependent enhancement of insulin secretion, inhibition of gastric emptying, and promotion of the survival and growth of insulin-producing beta-cells.
290	18941442	GLP-1, along with GLP-2 and oxyntomodulin, is produced in the intestinal L-cell via processing of proglucagon by prohormone convertase 1/3 (PC1/3), while in the pancreatic alpha-cell, coexpression of proglucagon and the alternate enzyme PC2 typically results in differential processing of proglucagon to yield glucagon.
291	18941442	In high fat-fed and db/db mice, PC1/3-, but not PC2-expressing alpha-cells improved glucose handling and transiently lowered fasting glucose levels, suggesting that continuous delivery of PC1/3-derived proglucagon products via cell therapy may be useful for diabetes treatment.
292	18941442	In addition, we show that long-term treatment with PC1/3-expressing, but not PC2-expressing, alpha-cells improved cold-induced thermogenesis in db/db mice, demonstrating a previously unappreciated effect of one or more PC1/3-derived alpha-cell products.
293	18941442	Transplantation of PC1/3-Expressing alpha-cells improves glucose handling and cold tolerance in leptin-resistant mice.
294	18941442	Glucagon-like peptide-1 (GLP-1) has received much attention as a new treatment for diabetes because of its multiple blood glucose-lowering effects, including glucose-dependent enhancement of insulin secretion, inhibition of gastric emptying, and promotion of the survival and growth of insulin-producing beta-cells.
295	18941442	GLP-1, along with GLP-2 and oxyntomodulin, is produced in the intestinal L-cell via processing of proglucagon by prohormone convertase 1/3 (PC1/3), while in the pancreatic alpha-cell, coexpression of proglucagon and the alternate enzyme PC2 typically results in differential processing of proglucagon to yield glucagon.
296	18941442	In high fat-fed and db/db mice, PC1/3-, but not PC2-expressing alpha-cells improved glucose handling and transiently lowered fasting glucose levels, suggesting that continuous delivery of PC1/3-derived proglucagon products via cell therapy may be useful for diabetes treatment.
297	18941442	In addition, we show that long-term treatment with PC1/3-expressing, but not PC2-expressing, alpha-cells improved cold-induced thermogenesis in db/db mice, demonstrating a previously unappreciated effect of one or more PC1/3-derived alpha-cell products.
298	18941442	Transplantation of PC1/3-Expressing alpha-cells improves glucose handling and cold tolerance in leptin-resistant mice.
299	18941442	Glucagon-like peptide-1 (GLP-1) has received much attention as a new treatment for diabetes because of its multiple blood glucose-lowering effects, including glucose-dependent enhancement of insulin secretion, inhibition of gastric emptying, and promotion of the survival and growth of insulin-producing beta-cells.
300	18941442	GLP-1, along with GLP-2 and oxyntomodulin, is produced in the intestinal L-cell via processing of proglucagon by prohormone convertase 1/3 (PC1/3), while in the pancreatic alpha-cell, coexpression of proglucagon and the alternate enzyme PC2 typically results in differential processing of proglucagon to yield glucagon.
301	18941442	In high fat-fed and db/db mice, PC1/3-, but not PC2-expressing alpha-cells improved glucose handling and transiently lowered fasting glucose levels, suggesting that continuous delivery of PC1/3-derived proglucagon products via cell therapy may be useful for diabetes treatment.
302	18941442	In addition, we show that long-term treatment with PC1/3-expressing, but not PC2-expressing, alpha-cells improved cold-induced thermogenesis in db/db mice, demonstrating a previously unappreciated effect of one or more PC1/3-derived alpha-cell products.
303	19364070	Engrafted beta-cells showed positive carboxypeptidase E (CPE) and prohormone convertase 1 (PC1) staining, while prohormone convertase 2 (PC2) was undetectable.
304	19364070	Cell cycle inhibitors p16(INK4), p21(WAF1), and p27(Kip1) were abundantly expressed in the islet grafts and showed a predominant nuclear localization.
305	19364070	In conclusion, diabetic nude mice transplanted with human islets showed disproportionate hyperproinsulinemia and graft evidence of beta-cell restricted PC2 depletion, amyloid deposition and beta-cell death, and lack of beta-cell replication with nuclear translocation of p27(Kip1) and p21(WAF1) that together may contribute to delayed graft failure.
306	19364070	Engrafted beta-cells showed positive carboxypeptidase E (CPE) and prohormone convertase 1 (PC1) staining, while prohormone convertase 2 (PC2) was undetectable.
307	19364070	Cell cycle inhibitors p16(INK4), p21(WAF1), and p27(Kip1) were abundantly expressed in the islet grafts and showed a predominant nuclear localization.
308	19364070	In conclusion, diabetic nude mice transplanted with human islets showed disproportionate hyperproinsulinemia and graft evidence of beta-cell restricted PC2 depletion, amyloid deposition and beta-cell death, and lack of beta-cell replication with nuclear translocation of p27(Kip1) and p21(WAF1) that together may contribute to delayed graft failure.
309	20657753	Intraislet production of GLP-1 by activation of prohormone convertase 1/3 in pancreatic α-cells in mouse models of ß-cell regeneration.
310	20657753	The α-cells express both prohormone convertase 2 and 1/3 (PC 2 and PC 1/3, respectively), which resulted in the processing of the proglucagon precursor into glucagon-like peptide 1, thereby leading to local production of this important ß-cell growth factor.
311	20657753	Furthermore, while α-cells in the adult basically only express PC 2, significant activation of PC 1/3 is also observed in mouse models of insulin resistance such as pregnant, ob/ ob, db/db and prediabetic NOD mice, which may be a common mechanism in proliferating ß-cells.
312	21437630	Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population.
313	21437630	TCF7L2 and SLC30A8 have been found to be associated with type 2 diabetes mellitus (T2DM) as well as with impaired proinsulin processing recently, enzymes encoded by PCSK1 and PCSK2 are reported to play an important role in the process of proinsulin conversion.
314	21437630	To investigate whether the single nucleotide polymorphisms (SNPs) of TCF7L2, SLC30A8, PCSK1 and PCSK2 were associated with T2DM as well as with proinsulin conversion in a Han Chinese population from Chongqing.
315	21437630	A case-control study was performed in Han Chinese subjects with normal control (n=152) and T2DM (n=227), we genotyped rs7903146 and rs11196218 at TCF7L2, rs13266634 at SLC30A8, rs3811951 at PCSK1 and rs2021785 at PCSK2.
316	21437630	Rs13266634 at SLC30A8 had a tendency to be associated with fasting plasma levels of proinsulin (P=0.0639 in additive model).
317	21437630	Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population.
318	21437630	TCF7L2 and SLC30A8 have been found to be associated with type 2 diabetes mellitus (T2DM) as well as with impaired proinsulin processing recently, enzymes encoded by PCSK1 and PCSK2 are reported to play an important role in the process of proinsulin conversion.
319	21437630	To investigate whether the single nucleotide polymorphisms (SNPs) of TCF7L2, SLC30A8, PCSK1 and PCSK2 were associated with T2DM as well as with proinsulin conversion in a Han Chinese population from Chongqing.
320	21437630	A case-control study was performed in Han Chinese subjects with normal control (n=152) and T2DM (n=227), we genotyped rs7903146 and rs11196218 at TCF7L2, rs13266634 at SLC30A8, rs3811951 at PCSK1 and rs2021785 at PCSK2.
321	21437630	Rs13266634 at SLC30A8 had a tendency to be associated with fasting plasma levels of proinsulin (P=0.0639 in additive model).
322	21437630	Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population.
323	21437630	TCF7L2 and SLC30A8 have been found to be associated with type 2 diabetes mellitus (T2DM) as well as with impaired proinsulin processing recently, enzymes encoded by PCSK1 and PCSK2 are reported to play an important role in the process of proinsulin conversion.
324	21437630	To investigate whether the single nucleotide polymorphisms (SNPs) of TCF7L2, SLC30A8, PCSK1 and PCSK2 were associated with T2DM as well as with proinsulin conversion in a Han Chinese population from Chongqing.
325	21437630	A case-control study was performed in Han Chinese subjects with normal control (n=152) and T2DM (n=227), we genotyped rs7903146 and rs11196218 at TCF7L2, rs13266634 at SLC30A8, rs3811951 at PCSK1 and rs2021785 at PCSK2.
326	21437630	Rs13266634 at SLC30A8 had a tendency to be associated with fasting plasma levels of proinsulin (P=0.0639 in additive model).
327	21723250	To explore whether the perturbation of PIHO has a link to disproportionate hyperproinsulinemia, we investigated proinsulin conversion and the involved prohormone convertase 1/3 (PC1/3) and 2 (PC2) in mouse Ins2(+/Akita) islets/β-cells that preserve a primary PIHO disorder due to a mutation (C96Y) in the insulin 2 (Ins2) gene.
328	21723250	Histological, metabolic-labeling, and RT-PCR analyses revealed decreases of the PC1/3 and PC2 immunoreactivities in the β-cells of Ins2(+/Akita) islets in spite of no declines of these two convertases at the transcriptional and translational levels.
329	21723250	Immunoblot analyses in cloned Ins2(+/Akita) β-cells further confirmed the increased ratio of proinsulin to insulin despite the levels of PC1/3 and PC2 proteins were not reduced somehow.
330	21723250	To explore whether the perturbation of PIHO has a link to disproportionate hyperproinsulinemia, we investigated proinsulin conversion and the involved prohormone convertase 1/3 (PC1/3) and 2 (PC2) in mouse Ins2(+/Akita) islets/β-cells that preserve a primary PIHO disorder due to a mutation (C96Y) in the insulin 2 (Ins2) gene.
331	21723250	Histological, metabolic-labeling, and RT-PCR analyses revealed decreases of the PC1/3 and PC2 immunoreactivities in the β-cells of Ins2(+/Akita) islets in spite of no declines of these two convertases at the transcriptional and translational levels.
332	21723250	Immunoblot analyses in cloned Ins2(+/Akita) β-cells further confirmed the increased ratio of proinsulin to insulin despite the levels of PC1/3 and PC2 proteins were not reduced somehow.
333	21723250	To explore whether the perturbation of PIHO has a link to disproportionate hyperproinsulinemia, we investigated proinsulin conversion and the involved prohormone convertase 1/3 (PC1/3) and 2 (PC2) in mouse Ins2(+/Akita) islets/β-cells that preserve a primary PIHO disorder due to a mutation (C96Y) in the insulin 2 (Ins2) gene.
334	21723250	Histological, metabolic-labeling, and RT-PCR analyses revealed decreases of the PC1/3 and PC2 immunoreactivities in the β-cells of Ins2(+/Akita) islets in spite of no declines of these two convertases at the transcriptional and translational levels.
335	21723250	Immunoblot analyses in cloned Ins2(+/Akita) β-cells further confirmed the increased ratio of proinsulin to insulin despite the levels of PC1/3 and PC2 proteins were not reduced somehow.
336	21795304	Proglucagon is cleaved to glucagon by prohormone convertase 2 (PC2) in pancreatic α-cells, but is cleaved to glucagon-like peptide-1 (GLP-1) by PC1 in intestinal L-cells.
337	21795304	The aim of this study was to identify mechanisms which switch processing of proglucagon to generate GLP-1 in the pancreas, given that GLP-1 can increase insulin secretion and β-cell mass.
338	21795304	The α-cell line, αTC1-6, expressed PC1 at low levels and GLP-1 was detected in cells and in culture media.
339	21795304	Three G protein-coupled receptors, GPR120, TGR5 and GPR119, implicated in the release of GLP-1 from L-cells are expressed in αTC1-6 cells.
340	21795304	Incubation of these cells with an agonist of TGR5 increased PC1 promoter activity and GLP-1 secretion suggesting that this is a mechanism for switching processing to GLP-1 in the pancreas.
341	23011353	Effect of a common variant of the PCSK2 gene on reduced insulin secretion.
342	23306211	RT-PCR for endodermal and pancreatic lineage-specific markers was performed on AFS cells after adenovirally transduced expression of PDX1, NGN3 and MAFA.
343	23306211	Expression of MAFA was sufficient to induce insulin mRNA expression in nhpAFS cell lines, whereas a combination of MAFA, PDX1 and NGN3 further induced insulin expression, and also induced the expression of other important endocrine cell genes such as glucagon, NEUROD1, NKX2.2, ISL1 and PCSK2.
344	23306211	The expression of pancreatic genes such as NEUROD1, glucagon and insulin progressively decreased with the decline of adenovirally expressed PDX1, NGN3 and MAFA.
345	23451118	Identification of a small molecule that selectively inhibits mouse PC2 over mouse PC1/3: a computational and experimental study.
346	23451118	The calcium-dependent serine endoproteases prohormone convertase 1/3 (PC1/3) and prohormone convertase 2 (PC2) play important roles in the homeostatic regulation of blood glucose levels, hence implicated in diabetes mellitus.
347	23451118	Identification of a small molecule that selectively inhibits mouse PC2 over mouse PC1/3: a computational and experimental study.
348	23451118	The calcium-dependent serine endoproteases prohormone convertase 1/3 (PC1/3) and prohormone convertase 2 (PC2) play important roles in the homeostatic regulation of blood glucose levels, hence implicated in diabetes mellitus.
349	23985558	Exposure to 25 mM glucose significantly reduced insulin content (p<0.05) and glucokinase activity (p<0.01) after 72 h.
350	23985558	Effects of hyperglycemia on secretory function were accompanied by decreased mRNA expression of INS, GCK, PCSK1, PCSK2, PPP3CB, GJA1, ABCC8, and KCNJ11.
351	23985558	Hyperglycemia-induced apoptosis was evident from increased activity of caspase 3/7 and decreased BCL2 protein.
352	22169851	Inhibition of prohormone convertases PC1/3 and PC2 by 2,5-dideoxystreptamine derivatives.
353	22169851	The prohormone convertases PC1/3 and PC2 are eukaryotic serine proteases involved in the proteolytic maturation of peptide hormone precursors and are implicated in a variety of pathological conditions, including obesity, diabetes, and neurodegenerative diseases.
354	22169851	We identified four promising PC1/3 competitive inhibitors and three PC2 inhibitors that exhibited various inhibition mechanisms (competitive, noncompetitive, and mixed), with sub- and low micromolar inhibitory potency against a fluorogenic substrate.
355	22169851	We also identified compounds that were able to stimulate both 87 kDa PC1/3 and PC2 activity, behavior related to the presence of aryl groups on the dideoxystreptamine scaffold.
356	22169851	It is noteworthy that one compound was found to both inhibit PC2 and stimulate PC1/3.
357	22169851	Inhibition of prohormone convertases PC1/3 and PC2 by 2,5-dideoxystreptamine derivatives.
358	22169851	The prohormone convertases PC1/3 and PC2 are eukaryotic serine proteases involved in the proteolytic maturation of peptide hormone precursors and are implicated in a variety of pathological conditions, including obesity, diabetes, and neurodegenerative diseases.
359	22169851	We identified four promising PC1/3 competitive inhibitors and three PC2 inhibitors that exhibited various inhibition mechanisms (competitive, noncompetitive, and mixed), with sub- and low micromolar inhibitory potency against a fluorogenic substrate.
360	22169851	We also identified compounds that were able to stimulate both 87 kDa PC1/3 and PC2 activity, behavior related to the presence of aryl groups on the dideoxystreptamine scaffold.
361	22169851	It is noteworthy that one compound was found to both inhibit PC2 and stimulate PC1/3.
362	22169851	Inhibition of prohormone convertases PC1/3 and PC2 by 2,5-dideoxystreptamine derivatives.
363	22169851	The prohormone convertases PC1/3 and PC2 are eukaryotic serine proteases involved in the proteolytic maturation of peptide hormone precursors and are implicated in a variety of pathological conditions, including obesity, diabetes, and neurodegenerative diseases.
364	22169851	We identified four promising PC1/3 competitive inhibitors and three PC2 inhibitors that exhibited various inhibition mechanisms (competitive, noncompetitive, and mixed), with sub- and low micromolar inhibitory potency against a fluorogenic substrate.
365	22169851	We also identified compounds that were able to stimulate both 87 kDa PC1/3 and PC2 activity, behavior related to the presence of aryl groups on the dideoxystreptamine scaffold.
366	22169851	It is noteworthy that one compound was found to both inhibit PC2 and stimulate PC1/3.
367	22169851	Inhibition of prohormone convertases PC1/3 and PC2 by 2,5-dideoxystreptamine derivatives.
368	22169851	The prohormone convertases PC1/3 and PC2 are eukaryotic serine proteases involved in the proteolytic maturation of peptide hormone precursors and are implicated in a variety of pathological conditions, including obesity, diabetes, and neurodegenerative diseases.
369	22169851	We identified four promising PC1/3 competitive inhibitors and three PC2 inhibitors that exhibited various inhibition mechanisms (competitive, noncompetitive, and mixed), with sub- and low micromolar inhibitory potency against a fluorogenic substrate.
370	22169851	We also identified compounds that were able to stimulate both 87 kDa PC1/3 and PC2 activity, behavior related to the presence of aryl groups on the dideoxystreptamine scaffold.
371	22169851	It is noteworthy that one compound was found to both inhibit PC2 and stimulate PC1/3.
372	22169851	Inhibition of prohormone convertases PC1/3 and PC2 by 2,5-dideoxystreptamine derivatives.
373	22169851	The prohormone convertases PC1/3 and PC2 are eukaryotic serine proteases involved in the proteolytic maturation of peptide hormone precursors and are implicated in a variety of pathological conditions, including obesity, diabetes, and neurodegenerative diseases.
374	22169851	We identified four promising PC1/3 competitive inhibitors and three PC2 inhibitors that exhibited various inhibition mechanisms (competitive, noncompetitive, and mixed), with sub- and low micromolar inhibitory potency against a fluorogenic substrate.
375	22169851	We also identified compounds that were able to stimulate both 87 kDa PC1/3 and PC2 activity, behavior related to the presence of aryl groups on the dideoxystreptamine scaffold.
376	22169851	It is noteworthy that one compound was found to both inhibit PC2 and stimulate PC1/3.