Ignet

Gene Information

Gene symbol: INPPL1

Gene name: inositol polyphosphate phosphatase-like 1

HGNC ID: 6080

Synonyms: SHIP2

Related Genes

#	Gene Symbol	Number of hits
1	AKT1	1 hits
2	BCAR1	1 hits
3	CBL	1 hits
4	COL1A1	1 hits
5	EEA1	1 hits
6	EGF	1 hits
7	EGFR	1 hits
8	ENPP1	1 hits
9	GRB2	1 hits
10	IKBKB	1 hits
11	INPP5D	1 hits
12	INPP5E	1 hits
13	INS	1 hits
14	INSR	1 hits
15	MAPK8	1 hits
16	PHOX2A	1 hits
17	PI3	1 hits
18	PIB5PA	1 hits
19	PIK3CA	1 hits
20	PIK3CG	1 hits
21	PIK3R1	1 hits
22	PPP2R4	1 hits
23	PTEN	1 hits
24	PTPN1	1 hits
25	PTPRF	1 hits
26	PYGM	1 hits
27	RNF123	1 hits
28	SH2D5	1 hits
29	SHC1	1 hits
30	SLC2A4	1 hits
31	SNW1	1 hits
32	SRC	1 hits
33	SYNJ1	1 hits
34	TRIB3	1 hits

Related Sentences

#	PMID	Sentence
1	11343120	The lipid phosphatase SHIP2 controls insulin sensitivity.
2	11343120	In vitro studies have shown that SHIP2, in response to stimulation by numerous growth factors and insulin, is closely linked to signalling events mediated by both phosphoinositide-3-OH kinase and Ras/mitogen-activated protein kinase.
3	11343120	Loss of SHIP2 leads to increased sensitivity to insulin, which is characterized by severe neonatal hypoglycaemia, deregulated expression of the genes involved in gluconeogenesis, and perinatal death.
4	11343120	Adult mice that are heterozygous for the SHIP2 mutation have increased glucose tolerance and insulin sensitivity associated with an increased recruitment of the GLUT4 glucose transporter and increased glycogen synthesis in skeletal muscles.
5	11343120	Our results show that SHIP2 is a potent negative regulator of insulin signalling and insulin sensitivity in vivo.
6	11343120	The lipid phosphatase SHIP2 controls insulin sensitivity.
7	11343120	In vitro studies have shown that SHIP2, in response to stimulation by numerous growth factors and insulin, is closely linked to signalling events mediated by both phosphoinositide-3-OH kinase and Ras/mitogen-activated protein kinase.
8	11343120	Loss of SHIP2 leads to increased sensitivity to insulin, which is characterized by severe neonatal hypoglycaemia, deregulated expression of the genes involved in gluconeogenesis, and perinatal death.
9	11343120	Adult mice that are heterozygous for the SHIP2 mutation have increased glucose tolerance and insulin sensitivity associated with an increased recruitment of the GLUT4 glucose transporter and increased glycogen synthesis in skeletal muscles.
10	11343120	Our results show that SHIP2 is a potent negative regulator of insulin signalling and insulin sensitivity in vivo.
11	11343120	The lipid phosphatase SHIP2 controls insulin sensitivity.
12	11343120	In vitro studies have shown that SHIP2, in response to stimulation by numerous growth factors and insulin, is closely linked to signalling events mediated by both phosphoinositide-3-OH kinase and Ras/mitogen-activated protein kinase.
13	11343120	Loss of SHIP2 leads to increased sensitivity to insulin, which is characterized by severe neonatal hypoglycaemia, deregulated expression of the genes involved in gluconeogenesis, and perinatal death.
14	11343120	Adult mice that are heterozygous for the SHIP2 mutation have increased glucose tolerance and insulin sensitivity associated with an increased recruitment of the GLUT4 glucose transporter and increased glycogen synthesis in skeletal muscles.
15	11343120	Our results show that SHIP2 is a potent negative regulator of insulin signalling and insulin sensitivity in vivo.
16	11343120	The lipid phosphatase SHIP2 controls insulin sensitivity.
17	11343120	In vitro studies have shown that SHIP2, in response to stimulation by numerous growth factors and insulin, is closely linked to signalling events mediated by both phosphoinositide-3-OH kinase and Ras/mitogen-activated protein kinase.
18	11343120	Loss of SHIP2 leads to increased sensitivity to insulin, which is characterized by severe neonatal hypoglycaemia, deregulated expression of the genes involved in gluconeogenesis, and perinatal death.
19	11343120	Adult mice that are heterozygous for the SHIP2 mutation have increased glucose tolerance and insulin sensitivity associated with an increased recruitment of the GLUT4 glucose transporter and increased glycogen synthesis in skeletal muscles.
20	11343120	Our results show that SHIP2 is a potent negative regulator of insulin signalling and insulin sensitivity in vivo.
21	11343120	The lipid phosphatase SHIP2 controls insulin sensitivity.
22	11343120	In vitro studies have shown that SHIP2, in response to stimulation by numerous growth factors and insulin, is closely linked to signalling events mediated by both phosphoinositide-3-OH kinase and Ras/mitogen-activated protein kinase.
23	11343120	Loss of SHIP2 leads to increased sensitivity to insulin, which is characterized by severe neonatal hypoglycaemia, deregulated expression of the genes involved in gluconeogenesis, and perinatal death.
24	11343120	Adult mice that are heterozygous for the SHIP2 mutation have increased glucose tolerance and insulin sensitivity associated with an increased recruitment of the GLUT4 glucose transporter and increased glycogen synthesis in skeletal muscles.
25	11343120	Our results show that SHIP2 is a potent negative regulator of insulin signalling and insulin sensitivity in vivo.
26	11897556	Phosphoinositide 3-kinase (PI3K) plays a key role in insulin signaling and has been shown to be blunted in tissues of type 2 diabetes subjects.
27	11897556	There is emerging biochemical and, particularly, genetic evidence suggesting that insulin resistance can potentially be treated via modulation of PI3K by targeting PI3K itself or its up and down-stream modulators.
28	11897556	These potential targets include Src homology 2 domain containing inositol 5-phosphatase 2 (SHIP2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), kappaB kinase beta (IKKbeta), PKC isoforms, and the PI3K p85 subunit.
29	11897556	There is evidence suggesting that their inhibition affects PI3K activity and improves insulin sensitivity in vivo.
30	11897556	In the current review, we will discuss the role of these molecules in insulin-mediated activation of PI3K, the rational for targeting these molecules for diabetes treatment, and some critical issues in terms of drug development.
31	12086927	The lipid phosphatase SHIP2 is a potent negative regulator of insulin signaling and sensitivity in vivo and is thus a good candidate gene.
32	12145149	Association of SH2-containing inositol phosphatase 2 with the insulin resistance of diabetic db/db mice.
33	12145149	SH-2-containing inositol 5'-phosphatase 2 (SHIP-2) is a physiologically important lipid phosphatase that functions to hydrolyze phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P3 to PI(3,4)P2 in the negative regulation of insulin signaling.
34	12145149	We investigated whether SHIP-2 is associated with the insulin resistance of diabetic db/db mice.
35	12145149	In addition to the modest decrease at the level of PI 3-kinase, the activity of Akt and protein kinase C (PKC)-zeta/lambda, which are downstream molecules of PI 3-kinase, was more severely reduced in the skeletal muscle and fat tissue, but not in liver of db/db mice.
36	12145149	Treatment with the insulin-sensitizing agent rosiglitazone decreased the elevated expression of SHIP-2 in the skeletal muscle and fat tissue of db/db mice.
37	12145149	Insulin-induced Akt activation and PKC-zeta/lambda phosphorylation were restored to the control level, although insulin-stimulated PI 3-kinase activation was minimally affected in the skeletal muscle and fat tissue of db/db mice.
38	12145149	These results indicate that SHIP-2 is a novel molecule associated with insulin resistance in the skeletal muscle and fat tissue, and that insulin-induced activity of the downstream molecules of PI 3-kinase is decreased, at least in part, by the elevated expression of SHIP-2 in diabetic db/db mice.
39	12145149	Association of SH2-containing inositol phosphatase 2 with the insulin resistance of diabetic db/db mice.
40	12145149	SH-2-containing inositol 5'-phosphatase 2 (SHIP-2) is a physiologically important lipid phosphatase that functions to hydrolyze phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P3 to PI(3,4)P2 in the negative regulation of insulin signaling.
41	12145149	We investigated whether SHIP-2 is associated with the insulin resistance of diabetic db/db mice.
42	12145149	In addition to the modest decrease at the level of PI 3-kinase, the activity of Akt and protein kinase C (PKC)-zeta/lambda, which are downstream molecules of PI 3-kinase, was more severely reduced in the skeletal muscle and fat tissue, but not in liver of db/db mice.
43	12145149	Treatment with the insulin-sensitizing agent rosiglitazone decreased the elevated expression of SHIP-2 in the skeletal muscle and fat tissue of db/db mice.
44	12145149	Insulin-induced Akt activation and PKC-zeta/lambda phosphorylation were restored to the control level, although insulin-stimulated PI 3-kinase activation was minimally affected in the skeletal muscle and fat tissue of db/db mice.
45	12145149	These results indicate that SHIP-2 is a novel molecule associated with insulin resistance in the skeletal muscle and fat tissue, and that insulin-induced activity of the downstream molecules of PI 3-kinase is decreased, at least in part, by the elevated expression of SHIP-2 in diabetic db/db mice.
46	12145149	Association of SH2-containing inositol phosphatase 2 with the insulin resistance of diabetic db/db mice.
47	12145149	SH-2-containing inositol 5'-phosphatase 2 (SHIP-2) is a physiologically important lipid phosphatase that functions to hydrolyze phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P3 to PI(3,4)P2 in the negative regulation of insulin signaling.
48	12145149	We investigated whether SHIP-2 is associated with the insulin resistance of diabetic db/db mice.
49	12145149	In addition to the modest decrease at the level of PI 3-kinase, the activity of Akt and protein kinase C (PKC)-zeta/lambda, which are downstream molecules of PI 3-kinase, was more severely reduced in the skeletal muscle and fat tissue, but not in liver of db/db mice.
50	12145149	Treatment with the insulin-sensitizing agent rosiglitazone decreased the elevated expression of SHIP-2 in the skeletal muscle and fat tissue of db/db mice.
51	12145149	Insulin-induced Akt activation and PKC-zeta/lambda phosphorylation were restored to the control level, although insulin-stimulated PI 3-kinase activation was minimally affected in the skeletal muscle and fat tissue of db/db mice.
52	12145149	These results indicate that SHIP-2 is a novel molecule associated with insulin resistance in the skeletal muscle and fat tissue, and that insulin-induced activity of the downstream molecules of PI 3-kinase is decreased, at least in part, by the elevated expression of SHIP-2 in diabetic db/db mice.
53	12145149	Association of SH2-containing inositol phosphatase 2 with the insulin resistance of diabetic db/db mice.
54	12145149	SH-2-containing inositol 5'-phosphatase 2 (SHIP-2) is a physiologically important lipid phosphatase that functions to hydrolyze phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P3 to PI(3,4)P2 in the negative regulation of insulin signaling.
55	12145149	We investigated whether SHIP-2 is associated with the insulin resistance of diabetic db/db mice.
56	12145149	In addition to the modest decrease at the level of PI 3-kinase, the activity of Akt and protein kinase C (PKC)-zeta/lambda, which are downstream molecules of PI 3-kinase, was more severely reduced in the skeletal muscle and fat tissue, but not in liver of db/db mice.
57	12145149	Treatment with the insulin-sensitizing agent rosiglitazone decreased the elevated expression of SHIP-2 in the skeletal muscle and fat tissue of db/db mice.
58	12145149	Insulin-induced Akt activation and PKC-zeta/lambda phosphorylation were restored to the control level, although insulin-stimulated PI 3-kinase activation was minimally affected in the skeletal muscle and fat tissue of db/db mice.
59	12145149	These results indicate that SHIP-2 is a novel molecule associated with insulin resistance in the skeletal muscle and fat tissue, and that insulin-induced activity of the downstream molecules of PI 3-kinase is decreased, at least in part, by the elevated expression of SHIP-2 in diabetic db/db mice.
60	14683460	Phosphatidyl Inositol 3-Kinase (PI3K) is central to mediating insulin-s metabolic effects.
61	14683460	Inhibition of PI3K activity results in a blockade of insulin signaling including glucose uptake and glyocogen synthesis.
62	14683460	Mice lacking one of these enzymes, Src-Homology Inositol Phosphatase-2 (SHIP2), demonstrate increased insulin sensitivity, suggesting that pharmacological inhibition of SHIP2 could alleviate insulin resistance.
63	14683460	Recent studies demonstrate elevated SHIP2 expression is associated with insulin resistance in human patients.
64	14683460	Comparing the studies on SHIP2 and other phosphatases suggests how inhibition of SHIP2 leads to increased insulin sensitivity without deleterious effects.
65	14683460	This review focuses on the emergence of SHIP2 as a target in the insulin-signaling pathway for the treatment of type 2 diabetes.
66	14683460	Phosphatidyl Inositol 3-Kinase (PI3K) is central to mediating insulin-s metabolic effects.
67	14683460	Inhibition of PI3K activity results in a blockade of insulin signaling including glucose uptake and glyocogen synthesis.
68	14683460	Mice lacking one of these enzymes, Src-Homology Inositol Phosphatase-2 (SHIP2), demonstrate increased insulin sensitivity, suggesting that pharmacological inhibition of SHIP2 could alleviate insulin resistance.
69	14683460	Recent studies demonstrate elevated SHIP2 expression is associated with insulin resistance in human patients.
70	14683460	Comparing the studies on SHIP2 and other phosphatases suggests how inhibition of SHIP2 leads to increased insulin sensitivity without deleterious effects.
71	14683460	This review focuses on the emergence of SHIP2 as a target in the insulin-signaling pathway for the treatment of type 2 diabetes.
72	14683460	Phosphatidyl Inositol 3-Kinase (PI3K) is central to mediating insulin-s metabolic effects.
73	14683460	Inhibition of PI3K activity results in a blockade of insulin signaling including glucose uptake and glyocogen synthesis.
74	14683460	Mice lacking one of these enzymes, Src-Homology Inositol Phosphatase-2 (SHIP2), demonstrate increased insulin sensitivity, suggesting that pharmacological inhibition of SHIP2 could alleviate insulin resistance.
75	14683460	Recent studies demonstrate elevated SHIP2 expression is associated with insulin resistance in human patients.
76	14683460	Comparing the studies on SHIP2 and other phosphatases suggests how inhibition of SHIP2 leads to increased insulin sensitivity without deleterious effects.
77	14683460	This review focuses on the emergence of SHIP2 as a target in the insulin-signaling pathway for the treatment of type 2 diabetes.
78	14683460	Phosphatidyl Inositol 3-Kinase (PI3K) is central to mediating insulin-s metabolic effects.
79	14683460	Inhibition of PI3K activity results in a blockade of insulin signaling including glucose uptake and glyocogen synthesis.
80	14683460	Mice lacking one of these enzymes, Src-Homology Inositol Phosphatase-2 (SHIP2), demonstrate increased insulin sensitivity, suggesting that pharmacological inhibition of SHIP2 could alleviate insulin resistance.
81	14683460	Recent studies demonstrate elevated SHIP2 expression is associated with insulin resistance in human patients.
82	14683460	Comparing the studies on SHIP2 and other phosphatases suggests how inhibition of SHIP2 leads to increased insulin sensitivity without deleterious effects.
83	14683460	This review focuses on the emergence of SHIP2 as a target in the insulin-signaling pathway for the treatment of type 2 diabetes.
84	15220217	Type II SH2 domain-containing inositol 5-phosphatase (INPPL1, or SHIP2) plays an important role in the control of insulin sensitivity.
85	15668240	SH2-containing 5'-inositol phosphatase, SHIP2, regulates cytoskeleton organization and ligand-dependent down-regulation of the epidermal growth factor receptor.
86	15668240	SHIP2 down-regulates insulin signaling and is present at higher levels in diabetes and obesity.
87	15668240	SHIP2 associates with p130Cas and filamin, regulators of cell adhesion/migration and cytoskeleton, influencing cell adhesion/spreading.
88	15668240	Type I collagen specifically induces Src-mediated tyrosine phosphorylation of SHIP2.
89	15668240	Furthermore, decreased SHIP2 levels altered distribution of early endocytic antigen 1 (EEA1)-positive endocytic vesicles and of vesicles containing internalized epidermal growth factor (EGF) and transferrin.
90	15668240	EGF treatment of SHIP2 RNAi cells led to the following: enhanced EGF receptor (EGFR) degradation; increased EGFR ubiquitination; and increased association of EGFR with c-Cbl ubiquitin ligase.
91	15668240	Taken together, these experiments demonstrate that SHIP2 functions in the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation.
92	15668240	SH2-containing 5'-inositol phosphatase, SHIP2, regulates cytoskeleton organization and ligand-dependent down-regulation of the epidermal growth factor receptor.
93	15668240	SHIP2 down-regulates insulin signaling and is present at higher levels in diabetes and obesity.
94	15668240	SHIP2 associates with p130Cas and filamin, regulators of cell adhesion/migration and cytoskeleton, influencing cell adhesion/spreading.
95	15668240	Type I collagen specifically induces Src-mediated tyrosine phosphorylation of SHIP2.
96	15668240	Furthermore, decreased SHIP2 levels altered distribution of early endocytic antigen 1 (EEA1)-positive endocytic vesicles and of vesicles containing internalized epidermal growth factor (EGF) and transferrin.
97	15668240	EGF treatment of SHIP2 RNAi cells led to the following: enhanced EGF receptor (EGFR) degradation; increased EGFR ubiquitination; and increased association of EGFR with c-Cbl ubiquitin ligase.
98	15668240	Taken together, these experiments demonstrate that SHIP2 functions in the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation.
99	15668240	SH2-containing 5'-inositol phosphatase, SHIP2, regulates cytoskeleton organization and ligand-dependent down-regulation of the epidermal growth factor receptor.
100	15668240	SHIP2 down-regulates insulin signaling and is present at higher levels in diabetes and obesity.
101	15668240	SHIP2 associates with p130Cas and filamin, regulators of cell adhesion/migration and cytoskeleton, influencing cell adhesion/spreading.
102	15668240	Type I collagen specifically induces Src-mediated tyrosine phosphorylation of SHIP2.
103	15668240	Furthermore, decreased SHIP2 levels altered distribution of early endocytic antigen 1 (EEA1)-positive endocytic vesicles and of vesicles containing internalized epidermal growth factor (EGF) and transferrin.
104	15668240	EGF treatment of SHIP2 RNAi cells led to the following: enhanced EGF receptor (EGFR) degradation; increased EGFR ubiquitination; and increased association of EGFR with c-Cbl ubiquitin ligase.
105	15668240	Taken together, these experiments demonstrate that SHIP2 functions in the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation.
106	15668240	SH2-containing 5'-inositol phosphatase, SHIP2, regulates cytoskeleton organization and ligand-dependent down-regulation of the epidermal growth factor receptor.
107	15668240	SHIP2 down-regulates insulin signaling and is present at higher levels in diabetes and obesity.
108	15668240	SHIP2 associates with p130Cas and filamin, regulators of cell adhesion/migration and cytoskeleton, influencing cell adhesion/spreading.
109	15668240	Type I collagen specifically induces Src-mediated tyrosine phosphorylation of SHIP2.
110	15668240	Furthermore, decreased SHIP2 levels altered distribution of early endocytic antigen 1 (EEA1)-positive endocytic vesicles and of vesicles containing internalized epidermal growth factor (EGF) and transferrin.
111	15668240	EGF treatment of SHIP2 RNAi cells led to the following: enhanced EGF receptor (EGFR) degradation; increased EGFR ubiquitination; and increased association of EGFR with c-Cbl ubiquitin ligase.
112	15668240	Taken together, these experiments demonstrate that SHIP2 functions in the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation.
113	15668240	SH2-containing 5'-inositol phosphatase, SHIP2, regulates cytoskeleton organization and ligand-dependent down-regulation of the epidermal growth factor receptor.
114	15668240	SHIP2 down-regulates insulin signaling and is present at higher levels in diabetes and obesity.
115	15668240	SHIP2 associates with p130Cas and filamin, regulators of cell adhesion/migration and cytoskeleton, influencing cell adhesion/spreading.
116	15668240	Type I collagen specifically induces Src-mediated tyrosine phosphorylation of SHIP2.
117	15668240	Furthermore, decreased SHIP2 levels altered distribution of early endocytic antigen 1 (EEA1)-positive endocytic vesicles and of vesicles containing internalized epidermal growth factor (EGF) and transferrin.
118	15668240	EGF treatment of SHIP2 RNAi cells led to the following: enhanced EGF receptor (EGFR) degradation; increased EGFR ubiquitination; and increased association of EGFR with c-Cbl ubiquitin ligase.
119	15668240	Taken together, these experiments demonstrate that SHIP2 functions in the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation.
120	15668240	SH2-containing 5'-inositol phosphatase, SHIP2, regulates cytoskeleton organization and ligand-dependent down-regulation of the epidermal growth factor receptor.
121	15668240	SHIP2 down-regulates insulin signaling and is present at higher levels in diabetes and obesity.
122	15668240	SHIP2 associates with p130Cas and filamin, regulators of cell adhesion/migration and cytoskeleton, influencing cell adhesion/spreading.
123	15668240	Type I collagen specifically induces Src-mediated tyrosine phosphorylation of SHIP2.
124	15668240	Furthermore, decreased SHIP2 levels altered distribution of early endocytic antigen 1 (EEA1)-positive endocytic vesicles and of vesicles containing internalized epidermal growth factor (EGF) and transferrin.
125	15668240	EGF treatment of SHIP2 RNAi cells led to the following: enhanced EGF receptor (EGFR) degradation; increased EGFR ubiquitination; and increased association of EGFR with c-Cbl ubiquitin ligase.
126	15668240	Taken together, these experiments demonstrate that SHIP2 functions in the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation.
127	15668240	SH2-containing 5'-inositol phosphatase, SHIP2, regulates cytoskeleton organization and ligand-dependent down-regulation of the epidermal growth factor receptor.
128	15668240	SHIP2 down-regulates insulin signaling and is present at higher levels in diabetes and obesity.
129	15668240	SHIP2 associates with p130Cas and filamin, regulators of cell adhesion/migration and cytoskeleton, influencing cell adhesion/spreading.
130	15668240	Type I collagen specifically induces Src-mediated tyrosine phosphorylation of SHIP2.
131	15668240	Furthermore, decreased SHIP2 levels altered distribution of early endocytic antigen 1 (EEA1)-positive endocytic vesicles and of vesicles containing internalized epidermal growth factor (EGF) and transferrin.
132	15668240	EGF treatment of SHIP2 RNAi cells led to the following: enhanced EGF receptor (EGFR) degradation; increased EGFR ubiquitination; and increased association of EGFR with c-Cbl ubiquitin ligase.
133	15668240	Taken together, these experiments demonstrate that SHIP2 functions in the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation.
134	15687335	Impact of SRC homology 2-containing inositol 5'-phosphatase 2 gene polymorphisms detected in a Japanese population on insulin signaling.
135	15687335	Src homology 2-containing 5'-inositol phosphatase 2 (SHIP2) is known to be one of lipid phosphatases converting PI(3,4,5)P3 to PI(3,4)P2 in the negative regulation of insulin signaling with the fundamental impact on the state of insulin resistance.
136	15687335	Transfection study showed that expression of SNP3-SHIP2 inhibited insulin-induced PI(3,4,5)P3 production and Akt2 phosphorylation less potently than expression of wild-type SHIP2 in CHO-IR cells.
137	15687335	Insulin-induced tyrosine phosphorylation of SNP5-SHIP2 was decreased compared with that of wild-type SHIP2, resulting in increased Shc/Grb2 association and MAPK activation.
138	15687335	These results indicate that the polymorphisms of SHIP2 are implicated, at least in part, in type 2 diabetes, possibly by affecting the metabolic and/or mitogenic insulin signaling in the Japanese population.
139	15687335	Impact of SRC homology 2-containing inositol 5'-phosphatase 2 gene polymorphisms detected in a Japanese population on insulin signaling.
140	15687335	Src homology 2-containing 5'-inositol phosphatase 2 (SHIP2) is known to be one of lipid phosphatases converting PI(3,4,5)P3 to PI(3,4)P2 in the negative regulation of insulin signaling with the fundamental impact on the state of insulin resistance.
141	15687335	Transfection study showed that expression of SNP3-SHIP2 inhibited insulin-induced PI(3,4,5)P3 production and Akt2 phosphorylation less potently than expression of wild-type SHIP2 in CHO-IR cells.
142	15687335	Insulin-induced tyrosine phosphorylation of SNP5-SHIP2 was decreased compared with that of wild-type SHIP2, resulting in increased Shc/Grb2 association and MAPK activation.
143	15687335	These results indicate that the polymorphisms of SHIP2 are implicated, at least in part, in type 2 diabetes, possibly by affecting the metabolic and/or mitogenic insulin signaling in the Japanese population.
144	15687335	Impact of SRC homology 2-containing inositol 5'-phosphatase 2 gene polymorphisms detected in a Japanese population on insulin signaling.
145	15687335	Src homology 2-containing 5'-inositol phosphatase 2 (SHIP2) is known to be one of lipid phosphatases converting PI(3,4,5)P3 to PI(3,4)P2 in the negative regulation of insulin signaling with the fundamental impact on the state of insulin resistance.
146	15687335	Transfection study showed that expression of SNP3-SHIP2 inhibited insulin-induced PI(3,4,5)P3 production and Akt2 phosphorylation less potently than expression of wild-type SHIP2 in CHO-IR cells.
147	15687335	Insulin-induced tyrosine phosphorylation of SNP5-SHIP2 was decreased compared with that of wild-type SHIP2, resulting in increased Shc/Grb2 association and MAPK activation.
148	15687335	These results indicate that the polymorphisms of SHIP2 are implicated, at least in part, in type 2 diabetes, possibly by affecting the metabolic and/or mitogenic insulin signaling in the Japanese population.
149	15687335	Impact of SRC homology 2-containing inositol 5'-phosphatase 2 gene polymorphisms detected in a Japanese population on insulin signaling.
150	15687335	Src homology 2-containing 5'-inositol phosphatase 2 (SHIP2) is known to be one of lipid phosphatases converting PI(3,4,5)P3 to PI(3,4)P2 in the negative regulation of insulin signaling with the fundamental impact on the state of insulin resistance.
151	15687335	Transfection study showed that expression of SNP3-SHIP2 inhibited insulin-induced PI(3,4,5)P3 production and Akt2 phosphorylation less potently than expression of wild-type SHIP2 in CHO-IR cells.
152	15687335	Insulin-induced tyrosine phosphorylation of SNP5-SHIP2 was decreased compared with that of wild-type SHIP2, resulting in increased Shc/Grb2 association and MAPK activation.
153	15687335	These results indicate that the polymorphisms of SHIP2 are implicated, at least in part, in type 2 diabetes, possibly by affecting the metabolic and/or mitogenic insulin signaling in the Japanese population.
154	15964236	The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2.
155	15964236	The SH2 domain containing inositol polyphosphate 5-phosphatase-2 (SHIP2) hydrolyzes phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) generating phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2).
156	15964236	Overexpression of SHIP2 inhibits insulin-stimulated phosphoinositide 3-kinase (PI3K) dependent signaling events.
157	15964236	SHIP2 knockout mice were originally reported to show lethal neonatal hypoglycemia resulting from insulin hypersensitivity, but in addition to inactivating the SHIP2 gene, the Phox2a gene was also inadvertently deleted.
158	15964236	Another SHIP2 knockout mouse has now been generated which inactivates the SHIP2 gene but leaves Phox2a intact.
159	15964236	The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2.
160	15964236	The SH2 domain containing inositol polyphosphate 5-phosphatase-2 (SHIP2) hydrolyzes phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) generating phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2).
161	15964236	Overexpression of SHIP2 inhibits insulin-stimulated phosphoinositide 3-kinase (PI3K) dependent signaling events.
162	15964236	SHIP2 knockout mice were originally reported to show lethal neonatal hypoglycemia resulting from insulin hypersensitivity, but in addition to inactivating the SHIP2 gene, the Phox2a gene was also inadvertently deleted.
163	15964236	Another SHIP2 knockout mouse has now been generated which inactivates the SHIP2 gene but leaves Phox2a intact.
164	15964236	The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2.
165	15964236	The SH2 domain containing inositol polyphosphate 5-phosphatase-2 (SHIP2) hydrolyzes phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) generating phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2).
166	15964236	Overexpression of SHIP2 inhibits insulin-stimulated phosphoinositide 3-kinase (PI3K) dependent signaling events.
167	15964236	SHIP2 knockout mice were originally reported to show lethal neonatal hypoglycemia resulting from insulin hypersensitivity, but in addition to inactivating the SHIP2 gene, the Phox2a gene was also inadvertently deleted.
168	15964236	Another SHIP2 knockout mouse has now been generated which inactivates the SHIP2 gene but leaves Phox2a intact.
169	15964236	The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2.
170	15964236	The SH2 domain containing inositol polyphosphate 5-phosphatase-2 (SHIP2) hydrolyzes phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) generating phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2).
171	15964236	Overexpression of SHIP2 inhibits insulin-stimulated phosphoinositide 3-kinase (PI3K) dependent signaling events.
172	15964236	SHIP2 knockout mice were originally reported to show lethal neonatal hypoglycemia resulting from insulin hypersensitivity, but in addition to inactivating the SHIP2 gene, the Phox2a gene was also inadvertently deleted.
173	15964236	Another SHIP2 knockout mouse has now been generated which inactivates the SHIP2 gene but leaves Phox2a intact.
174	15964236	The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2.
175	15964236	The SH2 domain containing inositol polyphosphate 5-phosphatase-2 (SHIP2) hydrolyzes phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) generating phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2).
176	15964236	Overexpression of SHIP2 inhibits insulin-stimulated phosphoinositide 3-kinase (PI3K) dependent signaling events.
177	15964236	SHIP2 knockout mice were originally reported to show lethal neonatal hypoglycemia resulting from insulin hypersensitivity, but in addition to inactivating the SHIP2 gene, the Phox2a gene was also inadvertently deleted.
178	15964236	Another SHIP2 knockout mouse has now been generated which inactivates the SHIP2 gene but leaves Phox2a intact.
179	15983195	Impact of the liver-specific expression of SHIP2 (SH2-containing inositol 5'-phosphatase 2) on insulin signaling and glucose metabolism in mice.
180	15983195	We investigated the role of hepatic SH2-containing inositol 5'-phosphatase 2 (SHIP2) in glucose metabolism in mice.
181	15983195	Insulin-induced phosphorylation of Akt in liver was impaired in WT-SHIP2-expressing db/+m mice, whereas the reduced phosphorylation was restored in DeltaIP-SHIP2-expressing db/db mice.
182	15983195	The abundance of mRNA for glucose-6-phosphatase (G6Pase) and PEPCK was increased, that for glucokinase (GK) was unchanged, and that for sterol regulatory element-binding protein 1 (SREBP)-1 was decreased in hepatic WT-SHIP2-overexpressing db/+m mice.
183	15983195	Impact of the liver-specific expression of SHIP2 (SH2-containing inositol 5'-phosphatase 2) on insulin signaling and glucose metabolism in mice.
184	15983195	We investigated the role of hepatic SH2-containing inositol 5'-phosphatase 2 (SHIP2) in glucose metabolism in mice.
185	15983195	Insulin-induced phosphorylation of Akt in liver was impaired in WT-SHIP2-expressing db/+m mice, whereas the reduced phosphorylation was restored in DeltaIP-SHIP2-expressing db/db mice.
186	15983195	The abundance of mRNA for glucose-6-phosphatase (G6Pase) and PEPCK was increased, that for glucokinase (GK) was unchanged, and that for sterol regulatory element-binding protein 1 (SREBP)-1 was decreased in hepatic WT-SHIP2-overexpressing db/+m mice.
187	16582877	Here we review the evidence that lipid phosphatases, specifically PTEN and SHIP2, attenuate this important insulin signalling pathway.
188	16842857	Lipid phosphatases, src homology 2 domain containing inositol 5'-phosphatase 2 (SHIP2) and skeletal muscle and kidney-enriched inositol phosphatase (SKIP) hydrolyze PI(3,4,5)P(3) to PI(3,4)P(2) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) hydrolyzes PI(3,4,5)P(3) to PI(4,5)P(2).
189	16842857	SHIP2 negatively regulates insulin signaling relatively specifically via its 5'-phosphatase activity.
190	16842857	Targeted disruption of the SHIP2 gene in mice resulted in increased insulin sensitivity and conferred protection from obesity induced by a high-fat diet.
191	16842857	Polymorphisms in the human SHIP2 gene are associated, at least in part, with the insulin resistance of type 2 diabetes.
192	16842857	Importantly, inhibition of endogenous SHIP2 through the liver-specific expression of a dominant-negative SHIP2 improves glucose metabolism and insulin resistance in diabetic db/db mice.
193	16842857	Overexpression of PTEN and SKIP also inhibited insulin-induced phosphorylation of Akt and the uptake of glucose in cultured cells.
194	16842857	Taken together, inhibition of endogenous SHIP2 in the whole body appears to be effective at improving the insulin resistance associated with type 2 diabetes and/or obesity.
195	16842857	Inhibition of PTEN in the tissues specifically targeted, including skeletal muscle and fat, may result in an amelioration of insulin resistance in type 2 diabetes, although caution against the formation of tumors is needed.
196	16842857	Lipid phosphatases, src homology 2 domain containing inositol 5'-phosphatase 2 (SHIP2) and skeletal muscle and kidney-enriched inositol phosphatase (SKIP) hydrolyze PI(3,4,5)P(3) to PI(3,4)P(2) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) hydrolyzes PI(3,4,5)P(3) to PI(4,5)P(2).
197	16842857	SHIP2 negatively regulates insulin signaling relatively specifically via its 5'-phosphatase activity.
198	16842857	Targeted disruption of the SHIP2 gene in mice resulted in increased insulin sensitivity and conferred protection from obesity induced by a high-fat diet.
199	16842857	Polymorphisms in the human SHIP2 gene are associated, at least in part, with the insulin resistance of type 2 diabetes.
200	16842857	Importantly, inhibition of endogenous SHIP2 through the liver-specific expression of a dominant-negative SHIP2 improves glucose metabolism and insulin resistance in diabetic db/db mice.
201	16842857	Overexpression of PTEN and SKIP also inhibited insulin-induced phosphorylation of Akt and the uptake of glucose in cultured cells.
202	16842857	Taken together, inhibition of endogenous SHIP2 in the whole body appears to be effective at improving the insulin resistance associated with type 2 diabetes and/or obesity.
203	16842857	Inhibition of PTEN in the tissues specifically targeted, including skeletal muscle and fat, may result in an amelioration of insulin resistance in type 2 diabetes, although caution against the formation of tumors is needed.
204	16842857	Lipid phosphatases, src homology 2 domain containing inositol 5'-phosphatase 2 (SHIP2) and skeletal muscle and kidney-enriched inositol phosphatase (SKIP) hydrolyze PI(3,4,5)P(3) to PI(3,4)P(2) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) hydrolyzes PI(3,4,5)P(3) to PI(4,5)P(2).
205	16842857	SHIP2 negatively regulates insulin signaling relatively specifically via its 5'-phosphatase activity.
206	16842857	Targeted disruption of the SHIP2 gene in mice resulted in increased insulin sensitivity and conferred protection from obesity induced by a high-fat diet.
207	16842857	Polymorphisms in the human SHIP2 gene are associated, at least in part, with the insulin resistance of type 2 diabetes.
208	16842857	Importantly, inhibition of endogenous SHIP2 through the liver-specific expression of a dominant-negative SHIP2 improves glucose metabolism and insulin resistance in diabetic db/db mice.
209	16842857	Overexpression of PTEN and SKIP also inhibited insulin-induced phosphorylation of Akt and the uptake of glucose in cultured cells.
210	16842857	Taken together, inhibition of endogenous SHIP2 in the whole body appears to be effective at improving the insulin resistance associated with type 2 diabetes and/or obesity.
211	16842857	Inhibition of PTEN in the tissues specifically targeted, including skeletal muscle and fat, may result in an amelioration of insulin resistance in type 2 diabetes, although caution against the formation of tumors is needed.
212	16842857	Lipid phosphatases, src homology 2 domain containing inositol 5'-phosphatase 2 (SHIP2) and skeletal muscle and kidney-enriched inositol phosphatase (SKIP) hydrolyze PI(3,4,5)P(3) to PI(3,4)P(2) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) hydrolyzes PI(3,4,5)P(3) to PI(4,5)P(2).
213	16842857	SHIP2 negatively regulates insulin signaling relatively specifically via its 5'-phosphatase activity.
214	16842857	Targeted disruption of the SHIP2 gene in mice resulted in increased insulin sensitivity and conferred protection from obesity induced by a high-fat diet.
215	16842857	Polymorphisms in the human SHIP2 gene are associated, at least in part, with the insulin resistance of type 2 diabetes.
216	16842857	Importantly, inhibition of endogenous SHIP2 through the liver-specific expression of a dominant-negative SHIP2 improves glucose metabolism and insulin resistance in diabetic db/db mice.
217	16842857	Overexpression of PTEN and SKIP also inhibited insulin-induced phosphorylation of Akt and the uptake of glucose in cultured cells.
218	16842857	Taken together, inhibition of endogenous SHIP2 in the whole body appears to be effective at improving the insulin resistance associated with type 2 diabetes and/or obesity.
219	16842857	Inhibition of PTEN in the tissues specifically targeted, including skeletal muscle and fat, may result in an amelioration of insulin resistance in type 2 diabetes, although caution against the formation of tumors is needed.
220	16842857	Lipid phosphatases, src homology 2 domain containing inositol 5'-phosphatase 2 (SHIP2) and skeletal muscle and kidney-enriched inositol phosphatase (SKIP) hydrolyze PI(3,4,5)P(3) to PI(3,4)P(2) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) hydrolyzes PI(3,4,5)P(3) to PI(4,5)P(2).
221	16842857	SHIP2 negatively regulates insulin signaling relatively specifically via its 5'-phosphatase activity.
222	16842857	Targeted disruption of the SHIP2 gene in mice resulted in increased insulin sensitivity and conferred protection from obesity induced by a high-fat diet.
223	16842857	Polymorphisms in the human SHIP2 gene are associated, at least in part, with the insulin resistance of type 2 diabetes.
224	16842857	Importantly, inhibition of endogenous SHIP2 through the liver-specific expression of a dominant-negative SHIP2 improves glucose metabolism and insulin resistance in diabetic db/db mice.
225	16842857	Overexpression of PTEN and SKIP also inhibited insulin-induced phosphorylation of Akt and the uptake of glucose in cultured cells.
226	16842857	Taken together, inhibition of endogenous SHIP2 in the whole body appears to be effective at improving the insulin resistance associated with type 2 diabetes and/or obesity.
227	16842857	Inhibition of PTEN in the tissues specifically targeted, including skeletal muscle and fat, may result in an amelioration of insulin resistance in type 2 diabetes, although caution against the formation of tumors is needed.
228	16842857	Lipid phosphatases, src homology 2 domain containing inositol 5'-phosphatase 2 (SHIP2) and skeletal muscle and kidney-enriched inositol phosphatase (SKIP) hydrolyze PI(3,4,5)P(3) to PI(3,4)P(2) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) hydrolyzes PI(3,4,5)P(3) to PI(4,5)P(2).
229	16842857	SHIP2 negatively regulates insulin signaling relatively specifically via its 5'-phosphatase activity.
230	16842857	Targeted disruption of the SHIP2 gene in mice resulted in increased insulin sensitivity and conferred protection from obesity induced by a high-fat diet.
231	16842857	Polymorphisms in the human SHIP2 gene are associated, at least in part, with the insulin resistance of type 2 diabetes.
232	16842857	Importantly, inhibition of endogenous SHIP2 through the liver-specific expression of a dominant-negative SHIP2 improves glucose metabolism and insulin resistance in diabetic db/db mice.
233	16842857	Overexpression of PTEN and SKIP also inhibited insulin-induced phosphorylation of Akt and the uptake of glucose in cultured cells.
234	16842857	Taken together, inhibition of endogenous SHIP2 in the whole body appears to be effective at improving the insulin resistance associated with type 2 diabetes and/or obesity.
235	16842857	Inhibition of PTEN in the tissues specifically targeted, including skeletal muscle and fat, may result in an amelioration of insulin resistance in type 2 diabetes, although caution against the formation of tumors is needed.
236	16931451	PTEN and SHIP2 phosphoinositide phosphatases as negative regulators of insulin signalling.
237	16931451	In particular, the role of PTEN and SHIP2, two phosphoinositide phosphatases recently implicated as negative modulators of insulin signalling, is in focus.
238	16931451	Current knowledge on the role of PTEN and SHIP2 in insulin resistance, type II diabetes and related disorders will also be discussed.
239	16931451	PTEN and SHIP2 phosphoinositide phosphatases as negative regulators of insulin signalling.
240	16931451	In particular, the role of PTEN and SHIP2, two phosphoinositide phosphatases recently implicated as negative modulators of insulin signalling, is in focus.
241	16931451	Current knowledge on the role of PTEN and SHIP2 in insulin resistance, type II diabetes and related disorders will also be discussed.
242	16931451	PTEN and SHIP2 phosphoinositide phosphatases as negative regulators of insulin signalling.
243	16931451	In particular, the role of PTEN and SHIP2, two phosphoinositide phosphatases recently implicated as negative modulators of insulin signalling, is in focus.
244	16931451	Current knowledge on the role of PTEN and SHIP2 in insulin resistance, type II diabetes and related disorders will also be discussed.
245	16973905	APOE4-VLDL inhibits the HDL-activated phosphatidylinositol 3-kinase/Akt Pathway via the phosphoinositol phosphatase SHIP2.
246	16973905	We show that APOE4-VLDL diminishes the phosphorylation of Akt by HDL but does not alter phosphorylation of c-Jun N-terminal kinase, p38, or Src family kinases by HDL.
247	16973905	Furthermore APOE4-VLDL inhibits Akt phosphorylation by reducing the phosphatidylinositol 3-kinase product phosphatidylinositol-(3,4,5)-triphosphate (PI[3,4,5]P3).
248	16973905	Therefore the activation of SHIP2 by APOE4-VLDL, with the subsequent inhibition of the HDL/Akt pathway, is a novel and significant biological mechanism and may be a critical intermediate by which APOE4 increases the risk of atherosclerotic CVD.
249	17596404	Normalization of prandial blood glucose and improvement of glucose tolerance by liver-specific inhibition of SH2 domain containing inositol phosphatase 2 (SHIP2) in diabetic KKAy mice: SHIP2 inhibition causes insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis.
250	17596404	Recent data have established the lipid phosphatase SH2 domain-containing inositol phosphatase 2 (SHIP2) as a critical negative regulator of insulin signal transduction.
251	17596404	Liver-specific expression of a dominant-negative SHIP2 mutant in KKA(y) mice increased basal and insulin-stimulated Akt phosphorylation.
252	17596404	Furthermore, SHIP2 inhibition improved hepatic glycogen metabolism by modulating the phosphorylation states of glycogen phosphorylase and glycogen synthase, which ultimately increased hepatic glycogen content.
253	17596404	Enhanced glucokinase and reduced pyruvate dehydrogenase kinase 4 expression, together with increased plasma triglycerides, indicate improved glycolysis.
254	17596404	As a consequence of the insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis, the liver-specific inhibition of SHIP2 improved glucose tolerance and markedly reduced prandial blood glucose levels in KKA(y) mice.
255	17596404	Normalization of prandial blood glucose and improvement of glucose tolerance by liver-specific inhibition of SH2 domain containing inositol phosphatase 2 (SHIP2) in diabetic KKAy mice: SHIP2 inhibition causes insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis.
256	17596404	Recent data have established the lipid phosphatase SH2 domain-containing inositol phosphatase 2 (SHIP2) as a critical negative regulator of insulin signal transduction.
257	17596404	Liver-specific expression of a dominant-negative SHIP2 mutant in KKA(y) mice increased basal and insulin-stimulated Akt phosphorylation.
258	17596404	Furthermore, SHIP2 inhibition improved hepatic glycogen metabolism by modulating the phosphorylation states of glycogen phosphorylase and glycogen synthase, which ultimately increased hepatic glycogen content.
259	17596404	Enhanced glucokinase and reduced pyruvate dehydrogenase kinase 4 expression, together with increased plasma triglycerides, indicate improved glycolysis.
260	17596404	As a consequence of the insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis, the liver-specific inhibition of SHIP2 improved glucose tolerance and markedly reduced prandial blood glucose levels in KKA(y) mice.
261	17596404	Normalization of prandial blood glucose and improvement of glucose tolerance by liver-specific inhibition of SH2 domain containing inositol phosphatase 2 (SHIP2) in diabetic KKAy mice: SHIP2 inhibition causes insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis.
262	17596404	Recent data have established the lipid phosphatase SH2 domain-containing inositol phosphatase 2 (SHIP2) as a critical negative regulator of insulin signal transduction.
263	17596404	Liver-specific expression of a dominant-negative SHIP2 mutant in KKA(y) mice increased basal and insulin-stimulated Akt phosphorylation.
264	17596404	Furthermore, SHIP2 inhibition improved hepatic glycogen metabolism by modulating the phosphorylation states of glycogen phosphorylase and glycogen synthase, which ultimately increased hepatic glycogen content.
265	17596404	Enhanced glucokinase and reduced pyruvate dehydrogenase kinase 4 expression, together with increased plasma triglycerides, indicate improved glycolysis.
266	17596404	As a consequence of the insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis, the liver-specific inhibition of SHIP2 improved glucose tolerance and markedly reduced prandial blood glucose levels in KKA(y) mice.
267	17596404	Normalization of prandial blood glucose and improvement of glucose tolerance by liver-specific inhibition of SH2 domain containing inositol phosphatase 2 (SHIP2) in diabetic KKAy mice: SHIP2 inhibition causes insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis.
268	17596404	Recent data have established the lipid phosphatase SH2 domain-containing inositol phosphatase 2 (SHIP2) as a critical negative regulator of insulin signal transduction.
269	17596404	Liver-specific expression of a dominant-negative SHIP2 mutant in KKA(y) mice increased basal and insulin-stimulated Akt phosphorylation.
270	17596404	Furthermore, SHIP2 inhibition improved hepatic glycogen metabolism by modulating the phosphorylation states of glycogen phosphorylase and glycogen synthase, which ultimately increased hepatic glycogen content.
271	17596404	Enhanced glucokinase and reduced pyruvate dehydrogenase kinase 4 expression, together with increased plasma triglycerides, indicate improved glycolysis.
272	17596404	As a consequence of the insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis, the liver-specific inhibition of SHIP2 improved glucose tolerance and markedly reduced prandial blood glucose levels in KKA(y) mice.
273	17596404	Normalization of prandial blood glucose and improvement of glucose tolerance by liver-specific inhibition of SH2 domain containing inositol phosphatase 2 (SHIP2) in diabetic KKAy mice: SHIP2 inhibition causes insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis.
274	17596404	Recent data have established the lipid phosphatase SH2 domain-containing inositol phosphatase 2 (SHIP2) as a critical negative regulator of insulin signal transduction.
275	17596404	Liver-specific expression of a dominant-negative SHIP2 mutant in KKA(y) mice increased basal and insulin-stimulated Akt phosphorylation.
276	17596404	Furthermore, SHIP2 inhibition improved hepatic glycogen metabolism by modulating the phosphorylation states of glycogen phosphorylase and glycogen synthase, which ultimately increased hepatic glycogen content.
277	17596404	Enhanced glucokinase and reduced pyruvate dehydrogenase kinase 4 expression, together with increased plasma triglycerides, indicate improved glycolysis.
278	17596404	As a consequence of the insulin-mimetic effects on glycogen metabolism, gluconeogenesis, and glycolysis, the liver-specific inhibition of SHIP2 improved glucose tolerance and markedly reduced prandial blood glucose levels in KKA(y) mice.
279	17827708	Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions.
280	17827708	Activation of PI (phosphatidylinositol) 3-kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis.
281	17827708	The enzyme exists as a heterodimer containing a regulatory subunit and one of two widely-distributed isoforms of the p110 catalytic subunit: p110alpha or p110beta.
282	17827708	Activation of PI 3-kinase and its downstream AKT has been demonstrated to be essential for almost all of the insulin-induced glucose and lipid metabolism such as glucose uptake, glycogen synthesis, suppression of glucose output and triglyceride synthesis as well as insulin-induced mitogenesis.
283	17827708	In the obesity-induced insulin resistant condition, JNK and p70S6K are activated and phosphorylate IRS-proteins, which diminishes the insulin-induced tyrosine phosphorylation of IRS-proteins and thereby impairs the PI 3-kinase/AKT activations.
284	17827708	Thus, the drugs which restore the impaired insulin-induced PI 3-kinase/AKT activation, for example, by suppressing JNK or p70S6K, PTEN or SHIP2, could be novel agents to treat diabetes mellitus.
285	18039790	Impact of transgenic overexpression of SH2-containing inositol 5'-phosphatase 2 on glucose metabolism and insulin signaling in mice.
286	18039790	SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a 5'-lipid phosphatase hydrolyzing the phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P(3) to PI(3,4)P(2) in the regulation of insulin signaling, and is shown to be increased in peripheral tissues of diabetic C57BL/KSJ-db/db mice.
287	18039790	To clarify the impact of SHIP2 in the pathogenesis of insulin resistance with type 2 diabetes, we generated transgenic mice overexpressing SHIP2.
288	18039790	Insulin-induced phosphorylation of Akt was decreased in the SHIP2-overexpressing fat, skeletal muscle, and liver.
289	18039790	In addition, the expression of hepatic mRNAs for glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was increased, that for sterol regulatory element-binding protein 1 was unchanged, and that for glucokinase was decreased.
290	18039790	These results indicate that increased abundance of SHIP2 in vivo contributes, at least in part, to the impairment of glucose metabolism and insulin sensitivity on a normal chow diet, possibly by attenuating peripheral insulin signaling and by altering hepatic gene expression for glucose homeostasis.
291	18039790	Impact of transgenic overexpression of SH2-containing inositol 5'-phosphatase 2 on glucose metabolism and insulin signaling in mice.
292	18039790	SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a 5'-lipid phosphatase hydrolyzing the phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P(3) to PI(3,4)P(2) in the regulation of insulin signaling, and is shown to be increased in peripheral tissues of diabetic C57BL/KSJ-db/db mice.
293	18039790	To clarify the impact of SHIP2 in the pathogenesis of insulin resistance with type 2 diabetes, we generated transgenic mice overexpressing SHIP2.
294	18039790	Insulin-induced phosphorylation of Akt was decreased in the SHIP2-overexpressing fat, skeletal muscle, and liver.
295	18039790	In addition, the expression of hepatic mRNAs for glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was increased, that for sterol regulatory element-binding protein 1 was unchanged, and that for glucokinase was decreased.
296	18039790	These results indicate that increased abundance of SHIP2 in vivo contributes, at least in part, to the impairment of glucose metabolism and insulin sensitivity on a normal chow diet, possibly by attenuating peripheral insulin signaling and by altering hepatic gene expression for glucose homeostasis.
297	18039790	Impact of transgenic overexpression of SH2-containing inositol 5'-phosphatase 2 on glucose metabolism and insulin signaling in mice.
298	18039790	SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a 5'-lipid phosphatase hydrolyzing the phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P(3) to PI(3,4)P(2) in the regulation of insulin signaling, and is shown to be increased in peripheral tissues of diabetic C57BL/KSJ-db/db mice.
299	18039790	To clarify the impact of SHIP2 in the pathogenesis of insulin resistance with type 2 diabetes, we generated transgenic mice overexpressing SHIP2.
300	18039790	Insulin-induced phosphorylation of Akt was decreased in the SHIP2-overexpressing fat, skeletal muscle, and liver.
301	18039790	In addition, the expression of hepatic mRNAs for glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was increased, that for sterol regulatory element-binding protein 1 was unchanged, and that for glucokinase was decreased.
302	18039790	These results indicate that increased abundance of SHIP2 in vivo contributes, at least in part, to the impairment of glucose metabolism and insulin sensitivity on a normal chow diet, possibly by attenuating peripheral insulin signaling and by altering hepatic gene expression for glucose homeostasis.
303	18039790	Impact of transgenic overexpression of SH2-containing inositol 5'-phosphatase 2 on glucose metabolism and insulin signaling in mice.
304	18039790	SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a 5'-lipid phosphatase hydrolyzing the phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P(3) to PI(3,4)P(2) in the regulation of insulin signaling, and is shown to be increased in peripheral tissues of diabetic C57BL/KSJ-db/db mice.
305	18039790	To clarify the impact of SHIP2 in the pathogenesis of insulin resistance with type 2 diabetes, we generated transgenic mice overexpressing SHIP2.
306	18039790	Insulin-induced phosphorylation of Akt was decreased in the SHIP2-overexpressing fat, skeletal muscle, and liver.
307	18039790	In addition, the expression of hepatic mRNAs for glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was increased, that for sterol regulatory element-binding protein 1 was unchanged, and that for glucokinase was decreased.
308	18039790	These results indicate that increased abundance of SHIP2 in vivo contributes, at least in part, to the impairment of glucose metabolism and insulin sensitivity on a normal chow diet, possibly by attenuating peripheral insulin signaling and by altering hepatic gene expression for glucose homeostasis.
309	18061583	Inhibition of SH2-domain containing inositol phosphatase 2 (SHIP2) in insulin producing INS1E cells improves insulin signal transduction and induces proliferation.
310	18061583	Inhibition of the lipid phosphatase SH2-domain containing inositol phosphatase 2 (SHIP2) in L6-C10 muscle cells, in 3T3-L1 adipocytes and in the liver of db/db mice has been shown to ameliorate insulin signal transduction and established SHIP2 as a negative regulator of insulin action.
311	18061583	Here we show that SHIP2 inhibition in INS1E insulinoma cells increased Akt, glycogen synthase kinase 3 and extracellular signal-regulated kinases 1 and 2 phosphorylation.
312	18061583	Inhibition of SH2-domain containing inositol phosphatase 2 (SHIP2) in insulin producing INS1E cells improves insulin signal transduction and induces proliferation.
313	18061583	Inhibition of the lipid phosphatase SH2-domain containing inositol phosphatase 2 (SHIP2) in L6-C10 muscle cells, in 3T3-L1 adipocytes and in the liver of db/db mice has been shown to ameliorate insulin signal transduction and established SHIP2 as a negative regulator of insulin action.
314	18061583	Here we show that SHIP2 inhibition in INS1E insulinoma cells increased Akt, glycogen synthase kinase 3 and extracellular signal-regulated kinases 1 and 2 phosphorylation.
315	18061583	Inhibition of SH2-domain containing inositol phosphatase 2 (SHIP2) in insulin producing INS1E cells improves insulin signal transduction and induces proliferation.
316	18061583	Inhibition of the lipid phosphatase SH2-domain containing inositol phosphatase 2 (SHIP2) in L6-C10 muscle cells, in 3T3-L1 adipocytes and in the liver of db/db mice has been shown to ameliorate insulin signal transduction and established SHIP2 as a negative regulator of insulin action.
317	18061583	Here we show that SHIP2 inhibition in INS1E insulinoma cells increased Akt, glycogen synthase kinase 3 and extracellular signal-regulated kinases 1 and 2 phosphorylation.
318	19272022	Growth factor or insulin stimulation induces a canonical cascade resulting in the transient phosphorylation of PtdIns(4,5)P(2) by PI3K (phosphoinositide 3-kinase) to form PtdIns(3,4,5)P(3), which is rapidly dephosphorylated either by PTEN (phosphatase and tensin homologue deleted on chromosome 10) back to PtdIns(4,5)P(2), or by the 5-ptases (inositol polyphosphate 5-phosphatases), generating PtdIns(3,4)P(2).
319	19272022	Futhermore, the 5-ptases SHIP [SH2 (Src homology 2)-domain-containing inositol phosphatase] 2, SKIP (skeletal muscle- and kidney-enriched inositol phosphatase) and 72-5ptase (72 kDa 5-ptase)/Type IV/Inpp5e (inositol polyphosphate 5-phosphatase E) are implicated in negatively regulating insulin signalling and glucose homoeostasis in specific tissues.
320	19272022	SHIP2 polymorphisms are associated with a predisposition to insulin resistance.
321	19272022	In addition, 5-ptases such as SHIP1, SHIP2 and 72-5ptase/Type IV/Inpp5e regulate macrophage phagocytosis, and SHIP1 also controls haemopoietic cell proliferation.
322	19272022	Growth factor or insulin stimulation induces a canonical cascade resulting in the transient phosphorylation of PtdIns(4,5)P(2) by PI3K (phosphoinositide 3-kinase) to form PtdIns(3,4,5)P(3), which is rapidly dephosphorylated either by PTEN (phosphatase and tensin homologue deleted on chromosome 10) back to PtdIns(4,5)P(2), or by the 5-ptases (inositol polyphosphate 5-phosphatases), generating PtdIns(3,4)P(2).
323	19272022	Futhermore, the 5-ptases SHIP [SH2 (Src homology 2)-domain-containing inositol phosphatase] 2, SKIP (skeletal muscle- and kidney-enriched inositol phosphatase) and 72-5ptase (72 kDa 5-ptase)/Type IV/Inpp5e (inositol polyphosphate 5-phosphatase E) are implicated in negatively regulating insulin signalling and glucose homoeostasis in specific tissues.
324	19272022	SHIP2 polymorphisms are associated with a predisposition to insulin resistance.
325	19272022	In addition, 5-ptases such as SHIP1, SHIP2 and 72-5ptase/Type IV/Inpp5e regulate macrophage phagocytosis, and SHIP1 also controls haemopoietic cell proliferation.
326	19518129	SH2 domain-containing 5-inositol phosphatase (SHIP2) is implicated in the development of type 2 diabetes and cancer.
327	19518129	Using IP4 as a substrate, we show here that tyrosines 986, 987, and 1135 are critical for EGF-induced stimulation of SHIP2 activity.
328	19518129	SH2 domain-containing 5-inositol phosphatase (SHIP2) is implicated in the development of type 2 diabetes and cancer.
329	19518129	Using IP4 as a substrate, we show here that tyrosines 986, 987, and 1135 are critical for EGF-induced stimulation of SHIP2 activity.
330	20829391	The inositol phosphatase SHIP2 negatively regulates insulin/IGF-I actions implicated in neuroprotection and memory function in mouse brain.
331	20829391	In the present study, we found that SH2-containing inositol 5'-phosphatase 2 (SHIP2), a negative regulator of phosphatidylinositol 3,4,5-trisphosphate-mediated signals, is widely expressed in adult mouse brain.
332	20829391	When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons.
333	20829391	To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt.
334	20829391	Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice.
335	20829391	These results suggest that SHIP2 is a potent negative regulator of insulin/IGF-I actions in the brain, and excess amounts of SHIP2 may be related, at least in part, to brain dysfunction in insulin resistance with type 2 diabetes.
336	20829391	The inositol phosphatase SHIP2 negatively regulates insulin/IGF-I actions implicated in neuroprotection and memory function in mouse brain.
337	20829391	In the present study, we found that SH2-containing inositol 5'-phosphatase 2 (SHIP2), a negative regulator of phosphatidylinositol 3,4,5-trisphosphate-mediated signals, is widely expressed in adult mouse brain.
338	20829391	When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons.
339	20829391	To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt.
340	20829391	Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice.
341	20829391	These results suggest that SHIP2 is a potent negative regulator of insulin/IGF-I actions in the brain, and excess amounts of SHIP2 may be related, at least in part, to brain dysfunction in insulin resistance with type 2 diabetes.
342	20829391	The inositol phosphatase SHIP2 negatively regulates insulin/IGF-I actions implicated in neuroprotection and memory function in mouse brain.
343	20829391	In the present study, we found that SH2-containing inositol 5'-phosphatase 2 (SHIP2), a negative regulator of phosphatidylinositol 3,4,5-trisphosphate-mediated signals, is widely expressed in adult mouse brain.
344	20829391	When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons.
345	20829391	To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt.
346	20829391	Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice.
347	20829391	These results suggest that SHIP2 is a potent negative regulator of insulin/IGF-I actions in the brain, and excess amounts of SHIP2 may be related, at least in part, to brain dysfunction in insulin resistance with type 2 diabetes.
348	20829391	The inositol phosphatase SHIP2 negatively regulates insulin/IGF-I actions implicated in neuroprotection and memory function in mouse brain.
349	20829391	In the present study, we found that SH2-containing inositol 5'-phosphatase 2 (SHIP2), a negative regulator of phosphatidylinositol 3,4,5-trisphosphate-mediated signals, is widely expressed in adult mouse brain.
350	20829391	When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons.
351	20829391	To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt.
352	20829391	Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice.
353	20829391	These results suggest that SHIP2 is a potent negative regulator of insulin/IGF-I actions in the brain, and excess amounts of SHIP2 may be related, at least in part, to brain dysfunction in insulin resistance with type 2 diabetes.
354	20829391	The inositol phosphatase SHIP2 negatively regulates insulin/IGF-I actions implicated in neuroprotection and memory function in mouse brain.
355	20829391	In the present study, we found that SH2-containing inositol 5'-phosphatase 2 (SHIP2), a negative regulator of phosphatidylinositol 3,4,5-trisphosphate-mediated signals, is widely expressed in adult mouse brain.
356	20829391	When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons.
357	20829391	To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt.
358	20829391	Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice.
359	20829391	These results suggest that SHIP2 is a potent negative regulator of insulin/IGF-I actions in the brain, and excess amounts of SHIP2 may be related, at least in part, to brain dysfunction in insulin resistance with type 2 diabetes.
360	20829391	The inositol phosphatase SHIP2 negatively regulates insulin/IGF-I actions implicated in neuroprotection and memory function in mouse brain.
361	20829391	In the present study, we found that SH2-containing inositol 5'-phosphatase 2 (SHIP2), a negative regulator of phosphatidylinositol 3,4,5-trisphosphate-mediated signals, is widely expressed in adult mouse brain.
362	20829391	When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons.
363	20829391	To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt.
364	20829391	Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice.
365	20829391	These results suggest that SHIP2 is a potent negative regulator of insulin/IGF-I actions in the brain, and excess amounts of SHIP2 may be related, at least in part, to brain dysfunction in insulin resistance with type 2 diabetes.
366	22328908	SRC homology 2 (SH2)-containing inositol 5'-phosphatase protein (SHIP2) is a potential target for type 2 diabetes.
367	22328908	The insulin-induced SHIP2 interaction with Shc is very important for the membrane localization and functioning of SHIP2.
368	22328908	There is a bidentate relationship between the two proteins where two domains each from SHIP2 and Shc are involved in mutual binding.
369	22328908	However in the present study, the SHIP2-SH2 domain binding with the phosphorylated tyrosine 317 on the collagen-homology (CH) domain of Shc, has been studied due to the indispensability of this interaction in SHIP2 localization.
370	22328908	SRC homology 2 (SH2)-containing inositol 5'-phosphatase protein (SHIP2) is a potential target for type 2 diabetes.
371	22328908	The insulin-induced SHIP2 interaction with Shc is very important for the membrane localization and functioning of SHIP2.
372	22328908	There is a bidentate relationship between the two proteins where two domains each from SHIP2 and Shc are involved in mutual binding.
373	22328908	However in the present study, the SHIP2-SH2 domain binding with the phosphorylated tyrosine 317 on the collagen-homology (CH) domain of Shc, has been studied due to the indispensability of this interaction in SHIP2 localization.
374	22328908	SRC homology 2 (SH2)-containing inositol 5'-phosphatase protein (SHIP2) is a potential target for type 2 diabetes.
375	22328908	The insulin-induced SHIP2 interaction with Shc is very important for the membrane localization and functioning of SHIP2.
376	22328908	There is a bidentate relationship between the two proteins where two domains each from SHIP2 and Shc are involved in mutual binding.
377	22328908	However in the present study, the SHIP2-SH2 domain binding with the phosphorylated tyrosine 317 on the collagen-homology (CH) domain of Shc, has been studied due to the indispensability of this interaction in SHIP2 localization.
378	22328908	SRC homology 2 (SH2)-containing inositol 5'-phosphatase protein (SHIP2) is a potential target for type 2 diabetes.
379	22328908	The insulin-induced SHIP2 interaction with Shc is very important for the membrane localization and functioning of SHIP2.
380	22328908	There is a bidentate relationship between the two proteins where two domains each from SHIP2 and Shc are involved in mutual binding.
381	22328908	However in the present study, the SHIP2-SH2 domain binding with the phosphorylated tyrosine 317 on the collagen-homology (CH) domain of Shc, has been studied due to the indispensability of this interaction in SHIP2 localization.
382	22533436	An association between metabolic syndrome and specific single-nucleotide polymorphisms (SNPs) in the gene INPPL1, encoding for SHIP2, a SH2 domain-containing inositol 5-phosphatase involved in insulin signaling, has been described.
383	22641604	Phosphoinositide (PI) phosphatases such as the SH2 domain-containing inositol 5-phosphatases 1/2 (SHIP1 and 2) are important signalling enzymes in human physiopathology.
384	22641604	Since a subunit of the Ser/Thr phosphatase PP2A has been shown to interact with SHIP2, a putative mechanism for reversing SHIP2 Ser/Thr phosphorylation can be anticipated.
385	22641604	This mechanism may be more broadly involved in regulating PI signalling in the case of synaptojanin1 or the phosphatase, tensin homolog, deleted on chromosome TEN.
386	22641604	Phosphoinositide (PI) phosphatases such as the SH2 domain-containing inositol 5-phosphatases 1/2 (SHIP1 and 2) are important signalling enzymes in human physiopathology.
387	22641604	Since a subunit of the Ser/Thr phosphatase PP2A has been shown to interact with SHIP2, a putative mechanism for reversing SHIP2 Ser/Thr phosphorylation can be anticipated.
388	22641604	This mechanism may be more broadly involved in regulating PI signalling in the case of synaptojanin1 or the phosphatase, tensin homolog, deleted on chromosome TEN.
389	23086422	The phosphoinositide phosphatases regulate PI3K/Akt signalling, insulin signalling, endocytosis, vesicle trafficking, cell migration, proliferation and apoptosis.
390	23086422	Genetic mutations in the 5-phosphatase INPP5E are causative of the ciliopathy syndromes Joubert and MORM, and mutations in the 5-phosphatase OCRL result in Lowe's syndrome and Dent 2 disease.
391	23086422	Additionally, polymorphisms in the 5-phosphatase SHIP2 confer diabetes susceptibility in specific populations, whereas reduced protein expression of SHIP1 is reported in several human leukaemias.
392	23086422	Mutations in one SAC phosphatase, SAC3/FIG4, results in the degenerative neuropathy, Charcot-Marie-Tooth disease.
393	23434638	Rational design and synthesis of 4-substituted 2-pyridin-2-ylamides with inhibitory effects on SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2).
394	23434638	Novel 4-substituted 2-pyridin-2-ylamides were developed using in-silico ligand-based drug design (LBDD) in an attempt to identify inhibitors of SH2-containing 5'-inositol phosphatase 2 (SHIP2), which is implicated in insulin-resistant type 2 diabetes.
395	23434638	CPDA was found to enhance in vitro insulin signaling through the Akt pathway more efficiently than the previously reported SHIP2 inhibitor AS1949490, and ameliorated abnormal glucose metabolism in diabetic (db/db) mice.
396	23434638	Rational design and synthesis of 4-substituted 2-pyridin-2-ylamides with inhibitory effects on SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2).
397	23434638	Novel 4-substituted 2-pyridin-2-ylamides were developed using in-silico ligand-based drug design (LBDD) in an attempt to identify inhibitors of SH2-containing 5'-inositol phosphatase 2 (SHIP2), which is implicated in insulin-resistant type 2 diabetes.
398	23434638	CPDA was found to enhance in vitro insulin signaling through the Akt pathway more efficiently than the previously reported SHIP2 inhibitor AS1949490, and ameliorated abnormal glucose metabolism in diabetic (db/db) mice.
399	23434638	Rational design and synthesis of 4-substituted 2-pyridin-2-ylamides with inhibitory effects on SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2).
400	23434638	Novel 4-substituted 2-pyridin-2-ylamides were developed using in-silico ligand-based drug design (LBDD) in an attempt to identify inhibitors of SH2-containing 5'-inositol phosphatase 2 (SHIP2), which is implicated in insulin-resistant type 2 diabetes.
401	23434638	CPDA was found to enhance in vitro insulin signaling through the Akt pathway more efficiently than the previously reported SHIP2 inhibitor AS1949490, and ameliorated abnormal glucose metabolism in diabetic (db/db) mice.
402	23762820	These proteins interfere with different steps in insulin-signaling: ENPP1/PC-1 and the phosphatases PTP1B and PTPRF/LAR inhibit the insulin receptor activation; INPPL1/SHIP-2 hydrolyzes PI3-kinase products, hampering the phosphoinositide-mediated downstream signaling; and TRIB3 binds the serine-threonine kinase Akt, reducing its phosphorylation levels.
403	23762820	While several variants have been described over the years for all these genes, solid evidence of an association with type 2 diabetes and related diseases seems to exist only for rs1044498 of the ENPP1 gene and for rs2295490 of the TRIB3 gene.