Ignet

Gene Information

Gene symbol: SOCS1

Gene name: suppressor of cytokine signaling 1

HGNC ID: 19383

Synonyms: SOCS-1, SSI-1, JAB, TIP3, Cish1

Related Genes

#	Gene Symbol	Number of hits
1	AKT1	1 hits
2	BAX	1 hits
3	BCL2	1 hits
4	BCL2L1	1 hits
5	CCL2	1 hits
6	CD8A	1 hits
7	CISH	1 hits
8	CNBP	1 hits
9	FAS	1 hits
10	FUS	1 hits
11	HMOX1	1 hits
12	HSPA1A	1 hits
13	IFNG	1 hits
14	IGF1	1 hits
15	IGF1R	1 hits
16	IL15	1 hits
17	IL1A	1 hits
18	IL1B	1 hits
19	IL1RL1	1 hits
20	INS	1 hits
21	INSR	1 hits
22	IRAK3	1 hits
23	IRS1	1 hits
24	IRS2	1 hits
25	JAK2	1 hits
26	JUN	1 hits
27	LEP	1 hits
28	MAPK14	1 hits
29	MAPK3	1 hits
30	MYD88	1 hits
31	NIT1	1 hits
32	NOS2A	1 hits
33	PIK3CG	1 hits
34	RNF123	1 hits
35	RPS27A	1 hits
36	SHC1	1 hits
37	SIGIRR	1 hits
38	SOCS2	1 hits
39	SOCS3	1 hits
40	SOCS5	1 hits
41	SOCS6	1 hits
42	SOCS7	1 hits
43	SOD2	1 hits
44	SREBF1	1 hits
45	STAT1	1 hits
46	STAT3	1 hits
47	STAT5A	1 hits
48	TNF	1 hits
49	TNFAIP3	1 hits
50	TOLLIP	1 hits

Related Sentences

#	PMID	Sentence
1	11027633	Liver-derived hyperleptinemia in obese rats caused only a 5-7% loss of body weight, compared to a 13% loss in normoleptinemic lean animals; but in actual grams of weight lost there was no significant difference between obese and lean groups, suggesting that a subset of cells remain leptin-sensitive in obesity. mRNA and protein of a putative leptin-resistance factor, suppressor of cytokine signaling (SOCS)-1 or -3, were both increased in white adipose tissues (WAT) of VMH and DIO rats.
2	11027633	Since transgenic overexpression of SOCS-3 in islets reduced the lipopenic effect of leptin by 75%, we conclude that the increased expression of SOCS-1 and -3 in WAT of rats with acquired obesity could have blocked leptin's lipopenic action in the leptin-resistant WAT population.
3	11027633	Liver-derived hyperleptinemia in obese rats caused only a 5-7% loss of body weight, compared to a 13% loss in normoleptinemic lean animals; but in actual grams of weight lost there was no significant difference between obese and lean groups, suggesting that a subset of cells remain leptin-sensitive in obesity. mRNA and protein of a putative leptin-resistance factor, suppressor of cytokine signaling (SOCS)-1 or -3, were both increased in white adipose tissues (WAT) of VMH and DIO rats.
4	11027633	Since transgenic overexpression of SOCS-3 in islets reduced the lipopenic effect of leptin by 75%, we conclude that the increased expression of SOCS-1 and -3 in WAT of rats with acquired obesity could have blocked leptin's lipopenic action in the leptin-resistant WAT population.
5	11342531	Cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, and hormones, such as growth hormone, are known to cause insulin resistance, but the mechanisms by which they inhibit the cellular response to insulin have not been elucidated.
6	11342531	SOCS proteins are therefore attractive candidates as mediators of cytokine-induced insulin resistance.
7	11342531	We have found that SOCS-1 and SOCS-6 interact with the IR when expressed in human hepatoma cells (HepG2) or in rat hepatoma cells overexpressing the human IR.
8	11342531	In SOCS-1-expressing cells, insulin treatment increases the extent of interaction with the IR, whereas in SOCS-6-expressing cells the association with the IR appears to require insulin treatment.
9	11342531	SOCS-1 and SOCS-6 do not inhibit insulin-dependent IR autophosphorylation, but both proteins inhibit insulin-dependent activation of ERK1/2 and protein kinase B in vivo and IR-directed phosphorylation of IRS-1 in vitro.
10	11342531	These results suggest that SOCS proteins may be inhibitors of IR signaling and could mediate cytokine-induced insulin resistance and contribute to the pathogenesis of type II diabetes.
11	11342531	Cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, and hormones, such as growth hormone, are known to cause insulin resistance, but the mechanisms by which they inhibit the cellular response to insulin have not been elucidated.
12	11342531	SOCS proteins are therefore attractive candidates as mediators of cytokine-induced insulin resistance.
13	11342531	We have found that SOCS-1 and SOCS-6 interact with the IR when expressed in human hepatoma cells (HepG2) or in rat hepatoma cells overexpressing the human IR.
14	11342531	In SOCS-1-expressing cells, insulin treatment increases the extent of interaction with the IR, whereas in SOCS-6-expressing cells the association with the IR appears to require insulin treatment.
15	11342531	SOCS-1 and SOCS-6 do not inhibit insulin-dependent IR autophosphorylation, but both proteins inhibit insulin-dependent activation of ERK1/2 and protein kinase B in vivo and IR-directed phosphorylation of IRS-1 in vitro.
16	11342531	These results suggest that SOCS proteins may be inhibitors of IR signaling and could mediate cytokine-induced insulin resistance and contribute to the pathogenesis of type II diabetes.
17	11342531	Cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, and hormones, such as growth hormone, are known to cause insulin resistance, but the mechanisms by which they inhibit the cellular response to insulin have not been elucidated.
18	11342531	SOCS proteins are therefore attractive candidates as mediators of cytokine-induced insulin resistance.
19	11342531	We have found that SOCS-1 and SOCS-6 interact with the IR when expressed in human hepatoma cells (HepG2) or in rat hepatoma cells overexpressing the human IR.
20	11342531	In SOCS-1-expressing cells, insulin treatment increases the extent of interaction with the IR, whereas in SOCS-6-expressing cells the association with the IR appears to require insulin treatment.
21	11342531	SOCS-1 and SOCS-6 do not inhibit insulin-dependent IR autophosphorylation, but both proteins inhibit insulin-dependent activation of ERK1/2 and protein kinase B in vivo and IR-directed phosphorylation of IRS-1 in vitro.
22	11342531	These results suggest that SOCS proteins may be inhibitors of IR signaling and could mediate cytokine-induced insulin resistance and contribute to the pathogenesis of type II diabetes.
23	11342558	SOCS-1 protein prevents Janus Kinase/STAT-dependent inhibition of beta cell insulin gene transcription and secretion in response to interferon-gamma.
24	11342558	Interferon (IFN)-gamma, tumor necrosis factor-alpha and interleukin (IL)-1 beta play important, although not completely defined, roles in these mechanisms.
25	11342558	Here, using the highly differentiated beta Tc-Tet insulin-secreting cell line, we showed that IFN-gamma dose- and time-dependently suppressed insulin synthesis and glucose-stimulated secretion.
26	11342558	As described previously IFN-gamma, in combination with IL-1 beta, also induces inducible NO synthase expression and apoptosis (Dupraz, P., Cottet, S., Hamburger, F., Dolci, W., Felley-Bosco, E., and Thorens, B. (2000) J.
27	11342558	To assess the role of the Janus kinase/signal transducer and activator of transcription (STAT) pathway in IFN-gamma intracellular signaling, we stably overexpressed SOCS-1 (suppressor of cytokine signaling-1) in the beta cell line.
28	11342558	We demonstrated that SOCS-1 suppressed cytokine-induced STAT-1 phosphorylation and increased cellular accumulation.
29	11342558	This was accompanied by a suppression of the effect of IFN-gamma on: (i) reduction in insulin promoter-luciferase reporter gene transcription, (ii) decrease in insulin mRNA and peptide content, and (iii) suppression of glucose-stimulated insulin secretion.
30	11342558	Furthermore, SOCS-1 also suppressed the cellular effects that require the combined presence of IL-1 beta and IFN-gamma: induction of nitric oxide production and apoptosis.
31	11342558	Together our data demonstrate that IFN-gamma is responsible for the cytokine-induced defect in insulin gene expression and secretion and that this effect can be completely blocked by constitutive inhibition of the Janus kinase/STAT pathway.
32	11342558	SOCS-1 protein prevents Janus Kinase/STAT-dependent inhibition of beta cell insulin gene transcription and secretion in response to interferon-gamma.
33	11342558	Interferon (IFN)-gamma, tumor necrosis factor-alpha and interleukin (IL)-1 beta play important, although not completely defined, roles in these mechanisms.
34	11342558	Here, using the highly differentiated beta Tc-Tet insulin-secreting cell line, we showed that IFN-gamma dose- and time-dependently suppressed insulin synthesis and glucose-stimulated secretion.
35	11342558	As described previously IFN-gamma, in combination with IL-1 beta, also induces inducible NO synthase expression and apoptosis (Dupraz, P., Cottet, S., Hamburger, F., Dolci, W., Felley-Bosco, E., and Thorens, B. (2000) J.
36	11342558	To assess the role of the Janus kinase/signal transducer and activator of transcription (STAT) pathway in IFN-gamma intracellular signaling, we stably overexpressed SOCS-1 (suppressor of cytokine signaling-1) in the beta cell line.
37	11342558	We demonstrated that SOCS-1 suppressed cytokine-induced STAT-1 phosphorylation and increased cellular accumulation.
38	11342558	This was accompanied by a suppression of the effect of IFN-gamma on: (i) reduction in insulin promoter-luciferase reporter gene transcription, (ii) decrease in insulin mRNA and peptide content, and (iii) suppression of glucose-stimulated insulin secretion.
39	11342558	Furthermore, SOCS-1 also suppressed the cellular effects that require the combined presence of IL-1 beta and IFN-gamma: induction of nitric oxide production and apoptosis.
40	11342558	Together our data demonstrate that IFN-gamma is responsible for the cytokine-induced defect in insulin gene expression and secretion and that this effect can be completely blocked by constitutive inhibition of the Janus kinase/STAT pathway.
41	11342558	SOCS-1 protein prevents Janus Kinase/STAT-dependent inhibition of beta cell insulin gene transcription and secretion in response to interferon-gamma.
42	11342558	Interferon (IFN)-gamma, tumor necrosis factor-alpha and interleukin (IL)-1 beta play important, although not completely defined, roles in these mechanisms.
43	11342558	Here, using the highly differentiated beta Tc-Tet insulin-secreting cell line, we showed that IFN-gamma dose- and time-dependently suppressed insulin synthesis and glucose-stimulated secretion.
44	11342558	As described previously IFN-gamma, in combination with IL-1 beta, also induces inducible NO synthase expression and apoptosis (Dupraz, P., Cottet, S., Hamburger, F., Dolci, W., Felley-Bosco, E., and Thorens, B. (2000) J.
45	11342558	To assess the role of the Janus kinase/signal transducer and activator of transcription (STAT) pathway in IFN-gamma intracellular signaling, we stably overexpressed SOCS-1 (suppressor of cytokine signaling-1) in the beta cell line.
46	11342558	We demonstrated that SOCS-1 suppressed cytokine-induced STAT-1 phosphorylation and increased cellular accumulation.
47	11342558	This was accompanied by a suppression of the effect of IFN-gamma on: (i) reduction in insulin promoter-luciferase reporter gene transcription, (ii) decrease in insulin mRNA and peptide content, and (iii) suppression of glucose-stimulated insulin secretion.
48	11342558	Furthermore, SOCS-1 also suppressed the cellular effects that require the combined presence of IL-1 beta and IFN-gamma: induction of nitric oxide production and apoptosis.
49	11342558	Together our data demonstrate that IFN-gamma is responsible for the cytokine-induced defect in insulin gene expression and secretion and that this effect can be completely blocked by constitutive inhibition of the Janus kinase/STAT pathway.
50	11342558	SOCS-1 protein prevents Janus Kinase/STAT-dependent inhibition of beta cell insulin gene transcription and secretion in response to interferon-gamma.
51	11342558	Interferon (IFN)-gamma, tumor necrosis factor-alpha and interleukin (IL)-1 beta play important, although not completely defined, roles in these mechanisms.
52	11342558	Here, using the highly differentiated beta Tc-Tet insulin-secreting cell line, we showed that IFN-gamma dose- and time-dependently suppressed insulin synthesis and glucose-stimulated secretion.
53	11342558	As described previously IFN-gamma, in combination with IL-1 beta, also induces inducible NO synthase expression and apoptosis (Dupraz, P., Cottet, S., Hamburger, F., Dolci, W., Felley-Bosco, E., and Thorens, B. (2000) J.
54	11342558	To assess the role of the Janus kinase/signal transducer and activator of transcription (STAT) pathway in IFN-gamma intracellular signaling, we stably overexpressed SOCS-1 (suppressor of cytokine signaling-1) in the beta cell line.
55	11342558	We demonstrated that SOCS-1 suppressed cytokine-induced STAT-1 phosphorylation and increased cellular accumulation.
56	11342558	This was accompanied by a suppression of the effect of IFN-gamma on: (i) reduction in insulin promoter-luciferase reporter gene transcription, (ii) decrease in insulin mRNA and peptide content, and (iii) suppression of glucose-stimulated insulin secretion.
57	11342558	Furthermore, SOCS-1 also suppressed the cellular effects that require the combined presence of IL-1 beta and IFN-gamma: induction of nitric oxide production and apoptosis.
58	11342558	Together our data demonstrate that IFN-gamma is responsible for the cytokine-induced defect in insulin gene expression and secretion and that this effect can be completely blocked by constitutive inhibition of the Janus kinase/STAT pathway.
59	11723057	In this study, we have shown that IFN-gamma signaling, measured by signal transducer and activator of transcription-1 (STAT1) activation and the expression of IFN-gamma-responsive genes, is persistent in beta-cells for as long as the cytokine is present.
60	11723057	Because members of the suppressor of cytokine signaling (SOCS) family may regulate the duration of IFN-gamma signaling, their expression was investigated in beta-cells.
61	11723057	We found that cytokine-inducible SH2-containing protein, SOCS-1, and SOCS-2 are expressed in primary islets and NIT-1 insulinoma cells, both at the mRNA and protein levels, after treatment with IFN-gamma and other proinflammatory cytokines.
62	11723057	Transfected SOCS-1 was found to inhibit responses to IFN-gamma in NIT-1 insulinoma cells, including STAT1 activation, class I major histocompatibility complex upregulation, and IFN-gamma-induced cell death, but only when expressed at levels higher than those found in untransfected cells.
63	11723057	Consistent with this, IFN-gamma signaling was not affected in SOCS-1-deficient beta-cells.
64	11723057	Therefore, persistent IFN-gamma signaling in beta-cells is associated with SOCS-1 expression that is not sufficient to terminate signaling.
65	11723057	Because overexpression of SOCS-1 can suppress responses to IFN-gamma, this may be a useful strategy for protecting beta-cells from cytotoxicity mediated by IFN-gamma and possibly other proinflammatory cytokines.
66	11723057	In this study, we have shown that IFN-gamma signaling, measured by signal transducer and activator of transcription-1 (STAT1) activation and the expression of IFN-gamma-responsive genes, is persistent in beta-cells for as long as the cytokine is present.
67	11723057	Because members of the suppressor of cytokine signaling (SOCS) family may regulate the duration of IFN-gamma signaling, their expression was investigated in beta-cells.
68	11723057	We found that cytokine-inducible SH2-containing protein, SOCS-1, and SOCS-2 are expressed in primary islets and NIT-1 insulinoma cells, both at the mRNA and protein levels, after treatment with IFN-gamma and other proinflammatory cytokines.
69	11723057	Transfected SOCS-1 was found to inhibit responses to IFN-gamma in NIT-1 insulinoma cells, including STAT1 activation, class I major histocompatibility complex upregulation, and IFN-gamma-induced cell death, but only when expressed at levels higher than those found in untransfected cells.
70	11723057	Consistent with this, IFN-gamma signaling was not affected in SOCS-1-deficient beta-cells.
71	11723057	Therefore, persistent IFN-gamma signaling in beta-cells is associated with SOCS-1 expression that is not sufficient to terminate signaling.
72	11723057	Because overexpression of SOCS-1 can suppress responses to IFN-gamma, this may be a useful strategy for protecting beta-cells from cytotoxicity mediated by IFN-gamma and possibly other proinflammatory cytokines.
73	11723057	In this study, we have shown that IFN-gamma signaling, measured by signal transducer and activator of transcription-1 (STAT1) activation and the expression of IFN-gamma-responsive genes, is persistent in beta-cells for as long as the cytokine is present.
74	11723057	Because members of the suppressor of cytokine signaling (SOCS) family may regulate the duration of IFN-gamma signaling, their expression was investigated in beta-cells.
75	11723057	We found that cytokine-inducible SH2-containing protein, SOCS-1, and SOCS-2 are expressed in primary islets and NIT-1 insulinoma cells, both at the mRNA and protein levels, after treatment with IFN-gamma and other proinflammatory cytokines.
76	11723057	Transfected SOCS-1 was found to inhibit responses to IFN-gamma in NIT-1 insulinoma cells, including STAT1 activation, class I major histocompatibility complex upregulation, and IFN-gamma-induced cell death, but only when expressed at levels higher than those found in untransfected cells.
77	11723057	Consistent with this, IFN-gamma signaling was not affected in SOCS-1-deficient beta-cells.
78	11723057	Therefore, persistent IFN-gamma signaling in beta-cells is associated with SOCS-1 expression that is not sufficient to terminate signaling.
79	11723057	Because overexpression of SOCS-1 can suppress responses to IFN-gamma, this may be a useful strategy for protecting beta-cells from cytotoxicity mediated by IFN-gamma and possibly other proinflammatory cytokines.
80	11723057	In this study, we have shown that IFN-gamma signaling, measured by signal transducer and activator of transcription-1 (STAT1) activation and the expression of IFN-gamma-responsive genes, is persistent in beta-cells for as long as the cytokine is present.
81	11723057	Because members of the suppressor of cytokine signaling (SOCS) family may regulate the duration of IFN-gamma signaling, their expression was investigated in beta-cells.
82	11723057	We found that cytokine-inducible SH2-containing protein, SOCS-1, and SOCS-2 are expressed in primary islets and NIT-1 insulinoma cells, both at the mRNA and protein levels, after treatment with IFN-gamma and other proinflammatory cytokines.
83	11723057	Transfected SOCS-1 was found to inhibit responses to IFN-gamma in NIT-1 insulinoma cells, including STAT1 activation, class I major histocompatibility complex upregulation, and IFN-gamma-induced cell death, but only when expressed at levels higher than those found in untransfected cells.
84	11723057	Consistent with this, IFN-gamma signaling was not affected in SOCS-1-deficient beta-cells.
85	11723057	Therefore, persistent IFN-gamma signaling in beta-cells is associated with SOCS-1 expression that is not sufficient to terminate signaling.
86	11723057	Because overexpression of SOCS-1 can suppress responses to IFN-gamma, this may be a useful strategy for protecting beta-cells from cytotoxicity mediated by IFN-gamma and possibly other proinflammatory cytokines.
87	11723057	In this study, we have shown that IFN-gamma signaling, measured by signal transducer and activator of transcription-1 (STAT1) activation and the expression of IFN-gamma-responsive genes, is persistent in beta-cells for as long as the cytokine is present.
88	11723057	Because members of the suppressor of cytokine signaling (SOCS) family may regulate the duration of IFN-gamma signaling, their expression was investigated in beta-cells.
89	11723057	We found that cytokine-inducible SH2-containing protein, SOCS-1, and SOCS-2 are expressed in primary islets and NIT-1 insulinoma cells, both at the mRNA and protein levels, after treatment with IFN-gamma and other proinflammatory cytokines.
90	11723057	Transfected SOCS-1 was found to inhibit responses to IFN-gamma in NIT-1 insulinoma cells, including STAT1 activation, class I major histocompatibility complex upregulation, and IFN-gamma-induced cell death, but only when expressed at levels higher than those found in untransfected cells.
91	11723057	Consistent with this, IFN-gamma signaling was not affected in SOCS-1-deficient beta-cells.
92	11723057	Therefore, persistent IFN-gamma signaling in beta-cells is associated with SOCS-1 expression that is not sufficient to terminate signaling.
93	11723057	Because overexpression of SOCS-1 can suppress responses to IFN-gamma, this may be a useful strategy for protecting beta-cells from cytotoxicity mediated by IFN-gamma and possibly other proinflammatory cytokines.
94	11856812	Decreased IR, IRS-1, and IRS-2 tyrosyl phosphorylation in response to insulin was found in skeletal muscle, whereas a chronic activation of the IRS-PI 3-kinase pathway was found in liver.
95	11856812	The induction of the expression of proteins that inhibit IR signaling such as suppressors of cytokine signaling (SOCS)-1 and -6 may also be involved in this alteration.
96	12032139	Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic beta cells to tumor necrosis factor.
97	12032139	By studying the effects of SOCS-1 deficiency, we investigated whether SOCS-1 is involved in preventing cytokine-induced death of pancreatic islet cells, a potential mechanism of insulin deficiency in autoimmune diabetes.
98	12032139	Tumor necrosis factor (TNF) + interferon-gamma (IFNgamma) was more potent at inducing cell death in SOCS-1-/- islets than in wild type.
99	12032139	Interleukin-1 + IFNgamma induced the same level of cell death in SOCS-1-/- and wild-type islets, suggesting that the sensitivity of islets to IFNgamma or interleukin-1-mediated cytotoxicity is not affected by SOCS-1 deficiency.
100	12032139	Additionally, SOCS-1-/- beta cells were responsive to lower concentrations of TNF measured by class I major histocompatibility complex up-regulation.
101	12032139	The TNF + IFNgamma damage of islets was mediated by inducible nitric-oxide synthase (iNOS), and increased iNOS expression and nitric oxide production were found in SOCS-1-/- islets following cytokine treatment.
102	12032139	A further analysis revealed that SOCS-1 deficiency results in augmented TNF signaling via the p38 mitogen-activated protein kinase pathway but not NFkappaB or c-Jun N-terminal kinase pathways.
103	12032139	Increased p38 signaling may be responsible for the increased iNOS expression in SOCS-1-/- islets.
104	12032139	Therefore, these findings provide evidence that physiological levels of SOCS-1 negatively regulate TNF signaling.
105	12032139	Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic beta cells to tumor necrosis factor.
106	12032139	By studying the effects of SOCS-1 deficiency, we investigated whether SOCS-1 is involved in preventing cytokine-induced death of pancreatic islet cells, a potential mechanism of insulin deficiency in autoimmune diabetes.
107	12032139	Tumor necrosis factor (TNF) + interferon-gamma (IFNgamma) was more potent at inducing cell death in SOCS-1-/- islets than in wild type.
108	12032139	Interleukin-1 + IFNgamma induced the same level of cell death in SOCS-1-/- and wild-type islets, suggesting that the sensitivity of islets to IFNgamma or interleukin-1-mediated cytotoxicity is not affected by SOCS-1 deficiency.
109	12032139	Additionally, SOCS-1-/- beta cells were responsive to lower concentrations of TNF measured by class I major histocompatibility complex up-regulation.
110	12032139	The TNF + IFNgamma damage of islets was mediated by inducible nitric-oxide synthase (iNOS), and increased iNOS expression and nitric oxide production were found in SOCS-1-/- islets following cytokine treatment.
111	12032139	A further analysis revealed that SOCS-1 deficiency results in augmented TNF signaling via the p38 mitogen-activated protein kinase pathway but not NFkappaB or c-Jun N-terminal kinase pathways.
112	12032139	Increased p38 signaling may be responsible for the increased iNOS expression in SOCS-1-/- islets.
113	12032139	Therefore, these findings provide evidence that physiological levels of SOCS-1 negatively regulate TNF signaling.
114	12032139	Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic beta cells to tumor necrosis factor.
115	12032139	By studying the effects of SOCS-1 deficiency, we investigated whether SOCS-1 is involved in preventing cytokine-induced death of pancreatic islet cells, a potential mechanism of insulin deficiency in autoimmune diabetes.
116	12032139	Tumor necrosis factor (TNF) + interferon-gamma (IFNgamma) was more potent at inducing cell death in SOCS-1-/- islets than in wild type.
117	12032139	Interleukin-1 + IFNgamma induced the same level of cell death in SOCS-1-/- and wild-type islets, suggesting that the sensitivity of islets to IFNgamma or interleukin-1-mediated cytotoxicity is not affected by SOCS-1 deficiency.
118	12032139	Additionally, SOCS-1-/- beta cells were responsive to lower concentrations of TNF measured by class I major histocompatibility complex up-regulation.
119	12032139	The TNF + IFNgamma damage of islets was mediated by inducible nitric-oxide synthase (iNOS), and increased iNOS expression and nitric oxide production were found in SOCS-1-/- islets following cytokine treatment.
120	12032139	A further analysis revealed that SOCS-1 deficiency results in augmented TNF signaling via the p38 mitogen-activated protein kinase pathway but not NFkappaB or c-Jun N-terminal kinase pathways.
121	12032139	Increased p38 signaling may be responsible for the increased iNOS expression in SOCS-1-/- islets.
122	12032139	Therefore, these findings provide evidence that physiological levels of SOCS-1 negatively regulate TNF signaling.
123	12032139	Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic beta cells to tumor necrosis factor.
124	12032139	By studying the effects of SOCS-1 deficiency, we investigated whether SOCS-1 is involved in preventing cytokine-induced death of pancreatic islet cells, a potential mechanism of insulin deficiency in autoimmune diabetes.
125	12032139	Tumor necrosis factor (TNF) + interferon-gamma (IFNgamma) was more potent at inducing cell death in SOCS-1-/- islets than in wild type.
126	12032139	Interleukin-1 + IFNgamma induced the same level of cell death in SOCS-1-/- and wild-type islets, suggesting that the sensitivity of islets to IFNgamma or interleukin-1-mediated cytotoxicity is not affected by SOCS-1 deficiency.
127	12032139	Additionally, SOCS-1-/- beta cells were responsive to lower concentrations of TNF measured by class I major histocompatibility complex up-regulation.
128	12032139	The TNF + IFNgamma damage of islets was mediated by inducible nitric-oxide synthase (iNOS), and increased iNOS expression and nitric oxide production were found in SOCS-1-/- islets following cytokine treatment.
129	12032139	A further analysis revealed that SOCS-1 deficiency results in augmented TNF signaling via the p38 mitogen-activated protein kinase pathway but not NFkappaB or c-Jun N-terminal kinase pathways.
130	12032139	Increased p38 signaling may be responsible for the increased iNOS expression in SOCS-1-/- islets.
131	12032139	Therefore, these findings provide evidence that physiological levels of SOCS-1 negatively regulate TNF signaling.
132	12032139	Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic beta cells to tumor necrosis factor.
133	12032139	By studying the effects of SOCS-1 deficiency, we investigated whether SOCS-1 is involved in preventing cytokine-induced death of pancreatic islet cells, a potential mechanism of insulin deficiency in autoimmune diabetes.
134	12032139	Tumor necrosis factor (TNF) + interferon-gamma (IFNgamma) was more potent at inducing cell death in SOCS-1-/- islets than in wild type.
135	12032139	Interleukin-1 + IFNgamma induced the same level of cell death in SOCS-1-/- and wild-type islets, suggesting that the sensitivity of islets to IFNgamma or interleukin-1-mediated cytotoxicity is not affected by SOCS-1 deficiency.
136	12032139	Additionally, SOCS-1-/- beta cells were responsive to lower concentrations of TNF measured by class I major histocompatibility complex up-regulation.
137	12032139	The TNF + IFNgamma damage of islets was mediated by inducible nitric-oxide synthase (iNOS), and increased iNOS expression and nitric oxide production were found in SOCS-1-/- islets following cytokine treatment.
138	12032139	A further analysis revealed that SOCS-1 deficiency results in augmented TNF signaling via the p38 mitogen-activated protein kinase pathway but not NFkappaB or c-Jun N-terminal kinase pathways.
139	12032139	Increased p38 signaling may be responsible for the increased iNOS expression in SOCS-1-/- islets.
140	12032139	Therefore, these findings provide evidence that physiological levels of SOCS-1 negatively regulate TNF signaling.
141	12032139	Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic beta cells to tumor necrosis factor.
142	12032139	By studying the effects of SOCS-1 deficiency, we investigated whether SOCS-1 is involved in preventing cytokine-induced death of pancreatic islet cells, a potential mechanism of insulin deficiency in autoimmune diabetes.
143	12032139	Tumor necrosis factor (TNF) + interferon-gamma (IFNgamma) was more potent at inducing cell death in SOCS-1-/- islets than in wild type.
144	12032139	Interleukin-1 + IFNgamma induced the same level of cell death in SOCS-1-/- and wild-type islets, suggesting that the sensitivity of islets to IFNgamma or interleukin-1-mediated cytotoxicity is not affected by SOCS-1 deficiency.
145	12032139	Additionally, SOCS-1-/- beta cells were responsive to lower concentrations of TNF measured by class I major histocompatibility complex up-regulation.
146	12032139	The TNF + IFNgamma damage of islets was mediated by inducible nitric-oxide synthase (iNOS), and increased iNOS expression and nitric oxide production were found in SOCS-1-/- islets following cytokine treatment.
147	12032139	A further analysis revealed that SOCS-1 deficiency results in augmented TNF signaling via the p38 mitogen-activated protein kinase pathway but not NFkappaB or c-Jun N-terminal kinase pathways.
148	12032139	Increased p38 signaling may be responsible for the increased iNOS expression in SOCS-1-/- islets.
149	12032139	Therefore, these findings provide evidence that physiological levels of SOCS-1 negatively regulate TNF signaling.
150	12032139	Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic beta cells to tumor necrosis factor.
151	12032139	By studying the effects of SOCS-1 deficiency, we investigated whether SOCS-1 is involved in preventing cytokine-induced death of pancreatic islet cells, a potential mechanism of insulin deficiency in autoimmune diabetes.
152	12032139	Tumor necrosis factor (TNF) + interferon-gamma (IFNgamma) was more potent at inducing cell death in SOCS-1-/- islets than in wild type.
153	12032139	Interleukin-1 + IFNgamma induced the same level of cell death in SOCS-1-/- and wild-type islets, suggesting that the sensitivity of islets to IFNgamma or interleukin-1-mediated cytotoxicity is not affected by SOCS-1 deficiency.
154	12032139	Additionally, SOCS-1-/- beta cells were responsive to lower concentrations of TNF measured by class I major histocompatibility complex up-regulation.
155	12032139	The TNF + IFNgamma damage of islets was mediated by inducible nitric-oxide synthase (iNOS), and increased iNOS expression and nitric oxide production were found in SOCS-1-/- islets following cytokine treatment.
156	12032139	A further analysis revealed that SOCS-1 deficiency results in augmented TNF signaling via the p38 mitogen-activated protein kinase pathway but not NFkappaB or c-Jun N-terminal kinase pathways.
157	12032139	Increased p38 signaling may be responsible for the increased iNOS expression in SOCS-1-/- islets.
158	12032139	Therefore, these findings provide evidence that physiological levels of SOCS-1 negatively regulate TNF signaling.
159	12032139	Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic beta cells to tumor necrosis factor.
160	12032139	By studying the effects of SOCS-1 deficiency, we investigated whether SOCS-1 is involved in preventing cytokine-induced death of pancreatic islet cells, a potential mechanism of insulin deficiency in autoimmune diabetes.
161	12032139	Tumor necrosis factor (TNF) + interferon-gamma (IFNgamma) was more potent at inducing cell death in SOCS-1-/- islets than in wild type.
162	12032139	Interleukin-1 + IFNgamma induced the same level of cell death in SOCS-1-/- and wild-type islets, suggesting that the sensitivity of islets to IFNgamma or interleukin-1-mediated cytotoxicity is not affected by SOCS-1 deficiency.
163	12032139	Additionally, SOCS-1-/- beta cells were responsive to lower concentrations of TNF measured by class I major histocompatibility complex up-regulation.
164	12032139	The TNF + IFNgamma damage of islets was mediated by inducible nitric-oxide synthase (iNOS), and increased iNOS expression and nitric oxide production were found in SOCS-1-/- islets following cytokine treatment.
165	12032139	A further analysis revealed that SOCS-1 deficiency results in augmented TNF signaling via the p38 mitogen-activated protein kinase pathway but not NFkappaB or c-Jun N-terminal kinase pathways.
166	12032139	Increased p38 signaling may be responsible for the increased iNOS expression in SOCS-1-/- islets.
167	12032139	Therefore, these findings provide evidence that physiological levels of SOCS-1 negatively regulate TNF signaling.
168	12032139	Suppressor of cytokine signaling-1 regulates the sensitivity of pancreatic beta cells to tumor necrosis factor.
169	12032139	By studying the effects of SOCS-1 deficiency, we investigated whether SOCS-1 is involved in preventing cytokine-induced death of pancreatic islet cells, a potential mechanism of insulin deficiency in autoimmune diabetes.
170	12032139	Tumor necrosis factor (TNF) + interferon-gamma (IFNgamma) was more potent at inducing cell death in SOCS-1-/- islets than in wild type.
171	12032139	Interleukin-1 + IFNgamma induced the same level of cell death in SOCS-1-/- and wild-type islets, suggesting that the sensitivity of islets to IFNgamma or interleukin-1-mediated cytotoxicity is not affected by SOCS-1 deficiency.
172	12032139	Additionally, SOCS-1-/- beta cells were responsive to lower concentrations of TNF measured by class I major histocompatibility complex up-regulation.
173	12032139	The TNF + IFNgamma damage of islets was mediated by inducible nitric-oxide synthase (iNOS), and increased iNOS expression and nitric oxide production were found in SOCS-1-/- islets following cytokine treatment.
174	12032139	A further analysis revealed that SOCS-1 deficiency results in augmented TNF signaling via the p38 mitogen-activated protein kinase pathway but not NFkappaB or c-Jun N-terminal kinase pathways.
175	12032139	Increased p38 signaling may be responsible for the increased iNOS expression in SOCS-1-/- islets.
176	12032139	Therefore, these findings provide evidence that physiological levels of SOCS-1 negatively regulate TNF signaling.
177	12228220	SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2.
178	12228220	We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation.
179	12228220	SOCS1 or SOCS3 bound both recombinant and endogenous IRS1 and IRS2 and promoted their ubiquitination and subsequent degradation in multiple cell types.
180	12228220	Mutations in the conserved SOCS box of SOCS1 abrogated its interaction with the elongin BC ubiquitin-ligase complex without affecting its binding to IRS1 or IRS2.
181	12228220	The SOCS1 mutants also failed to promote the ubiquitination and degradation of either IRS1 or IRS2.
182	12228220	Adenoviral-mediated expression of SOCS1 in mouse liver dramatically reduced hepatic IRS1 and IRS2 protein levels and caused glucose intolerance; by contrast, expression of the SOCS1 mutants had no effect.
183	12228220	Thus, SOCS-mediated degradation of IRS proteins, presumably via the elongin BC ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin resistance, providing a target for therapy.
184	12228220	SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2.
185	12228220	We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation.
186	12228220	SOCS1 or SOCS3 bound both recombinant and endogenous IRS1 and IRS2 and promoted their ubiquitination and subsequent degradation in multiple cell types.
187	12228220	Mutations in the conserved SOCS box of SOCS1 abrogated its interaction with the elongin BC ubiquitin-ligase complex without affecting its binding to IRS1 or IRS2.
188	12228220	The SOCS1 mutants also failed to promote the ubiquitination and degradation of either IRS1 or IRS2.
189	12228220	Adenoviral-mediated expression of SOCS1 in mouse liver dramatically reduced hepatic IRS1 and IRS2 protein levels and caused glucose intolerance; by contrast, expression of the SOCS1 mutants had no effect.
190	12228220	Thus, SOCS-mediated degradation of IRS proteins, presumably via the elongin BC ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin resistance, providing a target for therapy.
191	12228220	SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2.
192	12228220	We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation.
193	12228220	SOCS1 or SOCS3 bound both recombinant and endogenous IRS1 and IRS2 and promoted their ubiquitination and subsequent degradation in multiple cell types.
194	12228220	Mutations in the conserved SOCS box of SOCS1 abrogated its interaction with the elongin BC ubiquitin-ligase complex without affecting its binding to IRS1 or IRS2.
195	12228220	The SOCS1 mutants also failed to promote the ubiquitination and degradation of either IRS1 or IRS2.
196	12228220	Adenoviral-mediated expression of SOCS1 in mouse liver dramatically reduced hepatic IRS1 and IRS2 protein levels and caused glucose intolerance; by contrast, expression of the SOCS1 mutants had no effect.
197	12228220	Thus, SOCS-mediated degradation of IRS proteins, presumably via the elongin BC ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin resistance, providing a target for therapy.
198	12228220	SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2.
199	12228220	We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation.
200	12228220	SOCS1 or SOCS3 bound both recombinant and endogenous IRS1 and IRS2 and promoted their ubiquitination and subsequent degradation in multiple cell types.
201	12228220	Mutations in the conserved SOCS box of SOCS1 abrogated its interaction with the elongin BC ubiquitin-ligase complex without affecting its binding to IRS1 or IRS2.
202	12228220	The SOCS1 mutants also failed to promote the ubiquitination and degradation of either IRS1 or IRS2.
203	12228220	Adenoviral-mediated expression of SOCS1 in mouse liver dramatically reduced hepatic IRS1 and IRS2 protein levels and caused glucose intolerance; by contrast, expression of the SOCS1 mutants had no effect.
204	12228220	Thus, SOCS-mediated degradation of IRS proteins, presumably via the elongin BC ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin resistance, providing a target for therapy.
205	12228220	SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2.
206	12228220	We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation.
207	12228220	SOCS1 or SOCS3 bound both recombinant and endogenous IRS1 and IRS2 and promoted their ubiquitination and subsequent degradation in multiple cell types.
208	12228220	Mutations in the conserved SOCS box of SOCS1 abrogated its interaction with the elongin BC ubiquitin-ligase complex without affecting its binding to IRS1 or IRS2.
209	12228220	The SOCS1 mutants also failed to promote the ubiquitination and degradation of either IRS1 or IRS2.
210	12228220	Adenoviral-mediated expression of SOCS1 in mouse liver dramatically reduced hepatic IRS1 and IRS2 protein levels and caused glucose intolerance; by contrast, expression of the SOCS1 mutants had no effect.
211	12228220	Thus, SOCS-mediated degradation of IRS proteins, presumably via the elongin BC ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin resistance, providing a target for therapy.
212	12228220	SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2.
213	12228220	We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation.
214	12228220	SOCS1 or SOCS3 bound both recombinant and endogenous IRS1 and IRS2 and promoted their ubiquitination and subsequent degradation in multiple cell types.
215	12228220	Mutations in the conserved SOCS box of SOCS1 abrogated its interaction with the elongin BC ubiquitin-ligase complex without affecting its binding to IRS1 or IRS2.
216	12228220	The SOCS1 mutants also failed to promote the ubiquitination and degradation of either IRS1 or IRS2.
217	12228220	Adenoviral-mediated expression of SOCS1 in mouse liver dramatically reduced hepatic IRS1 and IRS2 protein levels and caused glucose intolerance; by contrast, expression of the SOCS1 mutants had no effect.
218	12228220	Thus, SOCS-mediated degradation of IRS proteins, presumably via the elongin BC ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin resistance, providing a target for therapy.
219	12847226	Thyrotropin-mediated repression of class II trans-activator expression in thyroid cells: involvement of STAT3 and suppressor of cytokine signaling.
220	12847226	Thyrotropin (TSH) represses IFN-gamma-induced CIITA expression by inhibiting type IV CIITA promoter activity through the suppression of STAT1 activation and IFN regulatory factor 1 induction.
221	12847226	This study found that TSH induces transcriptional activation of the STAT3 gene through the phosphorylation of STAT3 and CREB activation.
222	12847226	TSH induces SOCS-1 and SOCS-3, and TSH-mediated SOCS-3 induction was dependent on STAT3.
223	12847226	The cell line stably expressing the wild-type STAT3 showed a higher CIITA induction in response to IFN-gamma and also exhibited TSH repression of the IFN-gamma-mediated induction of CIITA.
224	12847226	However, TSH repression of the IFN-gamma-induced CIITA expression was not observed in FRTL-5 thyroid cells, which stably expresses the dominant negative forms of STAT3, STAT3-Y705F, and STAT3-S727A.
225	12882919	We demonstrated that mice harboring beta-cells that do not respond to IFN because of the expression of the suppressor of cytokine signaling-1 (SOCS-1) succumb to an acute form of type 1 diabetes after infection with CVB3.
226	14578288	We demonstrated that NOD mice harboring beta-cells expressing the suppressor of cytokine signaling-1 (SOCS-1), an inhibitor of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling, have a markedly reduced incidence of diabetes.
227	14578288	Disease protection correlates with suppression of cytokine-induced STAT-1 phosphorylation in SOCS-1-expressing beta-cells and with a reduced sensitivity of these cells to destruction by diabetogenic cells in vivo.
228	14578288	We demonstrated that NOD mice harboring beta-cells expressing the suppressor of cytokine signaling-1 (SOCS-1), an inhibitor of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling, have a markedly reduced incidence of diabetes.
229	14578288	Disease protection correlates with suppression of cytokine-induced STAT-1 phosphorylation in SOCS-1-expressing beta-cells and with a reduced sensitivity of these cells to destruction by diabetogenic cells in vivo.
230	15100317	Suppressor of cytokine signaling-1 overexpression protects pancreatic beta cells from CD8+ T cell-mediated autoimmune destruction.
231	15100317	SOCS-1 appeared to protect at least in part by inhibiting TNF- and IFN-gamma-induced Fas expression on beta cells.
232	15100317	Fas expression was up-regulated on beta cells in vivo in prediabetic NOD8.3 mice, and this was inhibited by SOCS-1.
233	15100317	Additionally, IFN-gamma-induced class I MHC up-regulation and TNF- and IFN-gamma-induced IL-15 expression by beta cells were inhibited by SOCS-1, which correlated with suppressed 8.3 T cell proliferation in vitro.
234	15100317	Our findings suggest that increasing SOCS-1 expression may be useful as a strategy to block CD8(+) T cell-mediated type 1 diabetes as well as to more generally prevent cytokine-dependent tissue destruction in inflammatory diseases.
235	15100317	Suppressor of cytokine signaling-1 overexpression protects pancreatic beta cells from CD8+ T cell-mediated autoimmune destruction.
236	15100317	SOCS-1 appeared to protect at least in part by inhibiting TNF- and IFN-gamma-induced Fas expression on beta cells.
237	15100317	Fas expression was up-regulated on beta cells in vivo in prediabetic NOD8.3 mice, and this was inhibited by SOCS-1.
238	15100317	Additionally, IFN-gamma-induced class I MHC up-regulation and TNF- and IFN-gamma-induced IL-15 expression by beta cells were inhibited by SOCS-1, which correlated with suppressed 8.3 T cell proliferation in vitro.
239	15100317	Our findings suggest that increasing SOCS-1 expression may be useful as a strategy to block CD8(+) T cell-mediated type 1 diabetes as well as to more generally prevent cytokine-dependent tissue destruction in inflammatory diseases.
240	15100317	Suppressor of cytokine signaling-1 overexpression protects pancreatic beta cells from CD8+ T cell-mediated autoimmune destruction.
241	15100317	SOCS-1 appeared to protect at least in part by inhibiting TNF- and IFN-gamma-induced Fas expression on beta cells.
242	15100317	Fas expression was up-regulated on beta cells in vivo in prediabetic NOD8.3 mice, and this was inhibited by SOCS-1.
243	15100317	Additionally, IFN-gamma-induced class I MHC up-regulation and TNF- and IFN-gamma-induced IL-15 expression by beta cells were inhibited by SOCS-1, which correlated with suppressed 8.3 T cell proliferation in vitro.
244	15100317	Our findings suggest that increasing SOCS-1 expression may be useful as a strategy to block CD8(+) T cell-mediated type 1 diabetes as well as to more generally prevent cytokine-dependent tissue destruction in inflammatory diseases.
245	15100317	Suppressor of cytokine signaling-1 overexpression protects pancreatic beta cells from CD8+ T cell-mediated autoimmune destruction.
246	15100317	SOCS-1 appeared to protect at least in part by inhibiting TNF- and IFN-gamma-induced Fas expression on beta cells.
247	15100317	Fas expression was up-regulated on beta cells in vivo in prediabetic NOD8.3 mice, and this was inhibited by SOCS-1.
248	15100317	Additionally, IFN-gamma-induced class I MHC up-regulation and TNF- and IFN-gamma-induced IL-15 expression by beta cells were inhibited by SOCS-1, which correlated with suppressed 8.3 T cell proliferation in vitro.
249	15100317	Our findings suggest that increasing SOCS-1 expression may be useful as a strategy to block CD8(+) T cell-mediated type 1 diabetes as well as to more generally prevent cytokine-dependent tissue destruction in inflammatory diseases.
250	15100317	Suppressor of cytokine signaling-1 overexpression protects pancreatic beta cells from CD8+ T cell-mediated autoimmune destruction.
251	15100317	SOCS-1 appeared to protect at least in part by inhibiting TNF- and IFN-gamma-induced Fas expression on beta cells.
252	15100317	Fas expression was up-regulated on beta cells in vivo in prediabetic NOD8.3 mice, and this was inhibited by SOCS-1.
253	15100317	Additionally, IFN-gamma-induced class I MHC up-regulation and TNF- and IFN-gamma-induced IL-15 expression by beta cells were inhibited by SOCS-1, which correlated with suppressed 8.3 T cell proliferation in vitro.
254	15100317	Our findings suggest that increasing SOCS-1 expression may be useful as a strategy to block CD8(+) T cell-mediated type 1 diabetes as well as to more generally prevent cytokine-dependent tissue destruction in inflammatory diseases.
255	15169905	Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms.
256	15169905	Here we show that in both obesity and lipopolysaccharide (LPS)-induced endotoxemia there is an increase in suppressor of cytokine signaling (SOCS) proteins, SOCS-1 and SOCS-3, in liver, muscle, and, to a lesser extent, fat.
257	15169905	Direct overexpression of SOCS-3 in liver by adenoviral-mediated gene transfer markedly decreases tyrosine phosphorylation of both IRS-1 and IRS-2, while SOCS-1 overexpression preferentially inhibits IRS-2 phosphorylation.
258	15169905	Neither affects IR phosphorylation, although both SOCS-1 and SOCS-3 bind to the insulin receptor in vivo in an insulin-dependent fashion.
259	15169905	Experiments with cultured cells expressing mutant insulin receptors reveal that SOCS-3 binds to Tyr960 of IR, a key residue for the recognition of IRS-1 and IRS-2, whereas SOCS-1 binds to the domain in the catalytic loop essential for IRS-2 recognition in vitro.
260	15169905	Moreover, overexpression of either SOCS-1 or SOCS-3 attenuates insulin-induced glycogen synthesis in L6 myotubes and activation of glucose uptake in 3T3L1 adipocytes.
261	15169905	By contrast, a reduction of SOCS-1 or SOCS-3 by antisense treatment partially restores tumor necrosis factor alpha-induced downregulation of tyrosine phosphorylation of IRS proteins in 3T3L1 adipocytes.
262	15169905	These data indicate that SOCS-1 and SOCS-3 act as negative regulators in insulin signaling and serve as one of the missing links between insulin resistance and cytokine signaling.
263	15169905	Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms.
264	15169905	Here we show that in both obesity and lipopolysaccharide (LPS)-induced endotoxemia there is an increase in suppressor of cytokine signaling (SOCS) proteins, SOCS-1 and SOCS-3, in liver, muscle, and, to a lesser extent, fat.
265	15169905	Direct overexpression of SOCS-3 in liver by adenoviral-mediated gene transfer markedly decreases tyrosine phosphorylation of both IRS-1 and IRS-2, while SOCS-1 overexpression preferentially inhibits IRS-2 phosphorylation.
266	15169905	Neither affects IR phosphorylation, although both SOCS-1 and SOCS-3 bind to the insulin receptor in vivo in an insulin-dependent fashion.
267	15169905	Experiments with cultured cells expressing mutant insulin receptors reveal that SOCS-3 binds to Tyr960 of IR, a key residue for the recognition of IRS-1 and IRS-2, whereas SOCS-1 binds to the domain in the catalytic loop essential for IRS-2 recognition in vitro.
268	15169905	Moreover, overexpression of either SOCS-1 or SOCS-3 attenuates insulin-induced glycogen synthesis in L6 myotubes and activation of glucose uptake in 3T3L1 adipocytes.
269	15169905	By contrast, a reduction of SOCS-1 or SOCS-3 by antisense treatment partially restores tumor necrosis factor alpha-induced downregulation of tyrosine phosphorylation of IRS proteins in 3T3L1 adipocytes.
270	15169905	These data indicate that SOCS-1 and SOCS-3 act as negative regulators in insulin signaling and serve as one of the missing links between insulin resistance and cytokine signaling.
271	15169905	Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms.
272	15169905	Here we show that in both obesity and lipopolysaccharide (LPS)-induced endotoxemia there is an increase in suppressor of cytokine signaling (SOCS) proteins, SOCS-1 and SOCS-3, in liver, muscle, and, to a lesser extent, fat.
273	15169905	Direct overexpression of SOCS-3 in liver by adenoviral-mediated gene transfer markedly decreases tyrosine phosphorylation of both IRS-1 and IRS-2, while SOCS-1 overexpression preferentially inhibits IRS-2 phosphorylation.
274	15169905	Neither affects IR phosphorylation, although both SOCS-1 and SOCS-3 bind to the insulin receptor in vivo in an insulin-dependent fashion.
275	15169905	Experiments with cultured cells expressing mutant insulin receptors reveal that SOCS-3 binds to Tyr960 of IR, a key residue for the recognition of IRS-1 and IRS-2, whereas SOCS-1 binds to the domain in the catalytic loop essential for IRS-2 recognition in vitro.
276	15169905	Moreover, overexpression of either SOCS-1 or SOCS-3 attenuates insulin-induced glycogen synthesis in L6 myotubes and activation of glucose uptake in 3T3L1 adipocytes.
277	15169905	By contrast, a reduction of SOCS-1 or SOCS-3 by antisense treatment partially restores tumor necrosis factor alpha-induced downregulation of tyrosine phosphorylation of IRS proteins in 3T3L1 adipocytes.
278	15169905	These data indicate that SOCS-1 and SOCS-3 act as negative regulators in insulin signaling and serve as one of the missing links between insulin resistance and cytokine signaling.
279	15169905	Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms.
280	15169905	Here we show that in both obesity and lipopolysaccharide (LPS)-induced endotoxemia there is an increase in suppressor of cytokine signaling (SOCS) proteins, SOCS-1 and SOCS-3, in liver, muscle, and, to a lesser extent, fat.
281	15169905	Direct overexpression of SOCS-3 in liver by adenoviral-mediated gene transfer markedly decreases tyrosine phosphorylation of both IRS-1 and IRS-2, while SOCS-1 overexpression preferentially inhibits IRS-2 phosphorylation.
282	15169905	Neither affects IR phosphorylation, although both SOCS-1 and SOCS-3 bind to the insulin receptor in vivo in an insulin-dependent fashion.
283	15169905	Experiments with cultured cells expressing mutant insulin receptors reveal that SOCS-3 binds to Tyr960 of IR, a key residue for the recognition of IRS-1 and IRS-2, whereas SOCS-1 binds to the domain in the catalytic loop essential for IRS-2 recognition in vitro.
284	15169905	Moreover, overexpression of either SOCS-1 or SOCS-3 attenuates insulin-induced glycogen synthesis in L6 myotubes and activation of glucose uptake in 3T3L1 adipocytes.
285	15169905	By contrast, a reduction of SOCS-1 or SOCS-3 by antisense treatment partially restores tumor necrosis factor alpha-induced downregulation of tyrosine phosphorylation of IRS proteins in 3T3L1 adipocytes.
286	15169905	These data indicate that SOCS-1 and SOCS-3 act as negative regulators in insulin signaling and serve as one of the missing links between insulin resistance and cytokine signaling.
287	15169905	Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms.
288	15169905	Here we show that in both obesity and lipopolysaccharide (LPS)-induced endotoxemia there is an increase in suppressor of cytokine signaling (SOCS) proteins, SOCS-1 and SOCS-3, in liver, muscle, and, to a lesser extent, fat.
289	15169905	Direct overexpression of SOCS-3 in liver by adenoviral-mediated gene transfer markedly decreases tyrosine phosphorylation of both IRS-1 and IRS-2, while SOCS-1 overexpression preferentially inhibits IRS-2 phosphorylation.
290	15169905	Neither affects IR phosphorylation, although both SOCS-1 and SOCS-3 bind to the insulin receptor in vivo in an insulin-dependent fashion.
291	15169905	Experiments with cultured cells expressing mutant insulin receptors reveal that SOCS-3 binds to Tyr960 of IR, a key residue for the recognition of IRS-1 and IRS-2, whereas SOCS-1 binds to the domain in the catalytic loop essential for IRS-2 recognition in vitro.
292	15169905	Moreover, overexpression of either SOCS-1 or SOCS-3 attenuates insulin-induced glycogen synthesis in L6 myotubes and activation of glucose uptake in 3T3L1 adipocytes.
293	15169905	By contrast, a reduction of SOCS-1 or SOCS-3 by antisense treatment partially restores tumor necrosis factor alpha-induced downregulation of tyrosine phosphorylation of IRS proteins in 3T3L1 adipocytes.
294	15169905	These data indicate that SOCS-1 and SOCS-3 act as negative regulators in insulin signaling and serve as one of the missing links between insulin resistance and cytokine signaling.
295	15169905	Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms.
296	15169905	Here we show that in both obesity and lipopolysaccharide (LPS)-induced endotoxemia there is an increase in suppressor of cytokine signaling (SOCS) proteins, SOCS-1 and SOCS-3, in liver, muscle, and, to a lesser extent, fat.
297	15169905	Direct overexpression of SOCS-3 in liver by adenoviral-mediated gene transfer markedly decreases tyrosine phosphorylation of both IRS-1 and IRS-2, while SOCS-1 overexpression preferentially inhibits IRS-2 phosphorylation.
298	15169905	Neither affects IR phosphorylation, although both SOCS-1 and SOCS-3 bind to the insulin receptor in vivo in an insulin-dependent fashion.
299	15169905	Experiments with cultured cells expressing mutant insulin receptors reveal that SOCS-3 binds to Tyr960 of IR, a key residue for the recognition of IRS-1 and IRS-2, whereas SOCS-1 binds to the domain in the catalytic loop essential for IRS-2 recognition in vitro.
300	15169905	Moreover, overexpression of either SOCS-1 or SOCS-3 attenuates insulin-induced glycogen synthesis in L6 myotubes and activation of glucose uptake in 3T3L1 adipocytes.
301	15169905	By contrast, a reduction of SOCS-1 or SOCS-3 by antisense treatment partially restores tumor necrosis factor alpha-induced downregulation of tyrosine phosphorylation of IRS proteins in 3T3L1 adipocytes.
302	15169905	These data indicate that SOCS-1 and SOCS-3 act as negative regulators in insulin signaling and serve as one of the missing links between insulin resistance and cytokine signaling.
303	15169905	Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms.
304	15169905	Here we show that in both obesity and lipopolysaccharide (LPS)-induced endotoxemia there is an increase in suppressor of cytokine signaling (SOCS) proteins, SOCS-1 and SOCS-3, in liver, muscle, and, to a lesser extent, fat.
305	15169905	Direct overexpression of SOCS-3 in liver by adenoviral-mediated gene transfer markedly decreases tyrosine phosphorylation of both IRS-1 and IRS-2, while SOCS-1 overexpression preferentially inhibits IRS-2 phosphorylation.
306	15169905	Neither affects IR phosphorylation, although both SOCS-1 and SOCS-3 bind to the insulin receptor in vivo in an insulin-dependent fashion.
307	15169905	Experiments with cultured cells expressing mutant insulin receptors reveal that SOCS-3 binds to Tyr960 of IR, a key residue for the recognition of IRS-1 and IRS-2, whereas SOCS-1 binds to the domain in the catalytic loop essential for IRS-2 recognition in vitro.
308	15169905	Moreover, overexpression of either SOCS-1 or SOCS-3 attenuates insulin-induced glycogen synthesis in L6 myotubes and activation of glucose uptake in 3T3L1 adipocytes.
309	15169905	By contrast, a reduction of SOCS-1 or SOCS-3 by antisense treatment partially restores tumor necrosis factor alpha-induced downregulation of tyrosine phosphorylation of IRS proteins in 3T3L1 adipocytes.
310	15169905	These data indicate that SOCS-1 and SOCS-3 act as negative regulators in insulin signaling and serve as one of the missing links between insulin resistance and cytokine signaling.
311	15169905	Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms.
312	15169905	Here we show that in both obesity and lipopolysaccharide (LPS)-induced endotoxemia there is an increase in suppressor of cytokine signaling (SOCS) proteins, SOCS-1 and SOCS-3, in liver, muscle, and, to a lesser extent, fat.
313	15169905	Direct overexpression of SOCS-3 in liver by adenoviral-mediated gene transfer markedly decreases tyrosine phosphorylation of both IRS-1 and IRS-2, while SOCS-1 overexpression preferentially inhibits IRS-2 phosphorylation.
314	15169905	Neither affects IR phosphorylation, although both SOCS-1 and SOCS-3 bind to the insulin receptor in vivo in an insulin-dependent fashion.
315	15169905	Experiments with cultured cells expressing mutant insulin receptors reveal that SOCS-3 binds to Tyr960 of IR, a key residue for the recognition of IRS-1 and IRS-2, whereas SOCS-1 binds to the domain in the catalytic loop essential for IRS-2 recognition in vitro.
316	15169905	Moreover, overexpression of either SOCS-1 or SOCS-3 attenuates insulin-induced glycogen synthesis in L6 myotubes and activation of glucose uptake in 3T3L1 adipocytes.
317	15169905	By contrast, a reduction of SOCS-1 or SOCS-3 by antisense treatment partially restores tumor necrosis factor alpha-induced downregulation of tyrosine phosphorylation of IRS proteins in 3T3L1 adipocytes.
318	15169905	These data indicate that SOCS-1 and SOCS-3 act as negative regulators in insulin signaling and serve as one of the missing links between insulin resistance and cytokine signaling.
319	15240880	Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c.
320	15240880	Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia.
321	15240880	In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity.
322	15240880	Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling.
323	15240880	Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c.
324	15240880	Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia.
325	15240880	In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity.
326	15240880	Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling.
327	15913829	Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c.
328	15913829	Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia.
329	15913829	In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity.
330	15913829	Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling.
331	15913829	Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c.
332	15913829	Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia.
333	15913829	In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity.
334	15913829	Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling.
335	15983045	Socs1 deficiency enhances hepatic insulin signaling.
336	15983045	In hyperinsulinemic clamp studies, however, Socs1-/- Ifng-/- mice had enhanced hepatic insulin sensitivity demonstrated by greater suppression of endogenous glucose production compared with controls with no difference in glucose disposal.
337	15983045	Socs1-/- Ifng-/- mice had elevated liver insulin receptor substrate 2 expression (IRS-2) and IRS-2 tyrosine phosphorylation.
338	15983045	Hepatic insulin sensitivity and IRS-2 levels play central roles in the pathogenesis of type 2 diabetes.
339	15983045	Socs1 deficiency increases IRS-2 expression and enhances hepatic insulin sensitivity in vivo indicating that inhibition of SOCS1 may be a logical strategy in type 2 diabetes.
340	15983045	Socs1 deficiency enhances hepatic insulin signaling.
341	15983045	In hyperinsulinemic clamp studies, however, Socs1-/- Ifng-/- mice had enhanced hepatic insulin sensitivity demonstrated by greater suppression of endogenous glucose production compared with controls with no difference in glucose disposal.
342	15983045	Socs1-/- Ifng-/- mice had elevated liver insulin receptor substrate 2 expression (IRS-2) and IRS-2 tyrosine phosphorylation.
343	15983045	Hepatic insulin sensitivity and IRS-2 levels play central roles in the pathogenesis of type 2 diabetes.
344	15983045	Socs1 deficiency increases IRS-2 expression and enhances hepatic insulin sensitivity in vivo indicating that inhibition of SOCS1 may be a logical strategy in type 2 diabetes.
345	15983045	Socs1 deficiency enhances hepatic insulin signaling.
346	15983045	In hyperinsulinemic clamp studies, however, Socs1-/- Ifng-/- mice had enhanced hepatic insulin sensitivity demonstrated by greater suppression of endogenous glucose production compared with controls with no difference in glucose disposal.
347	15983045	Socs1-/- Ifng-/- mice had elevated liver insulin receptor substrate 2 expression (IRS-2) and IRS-2 tyrosine phosphorylation.
348	15983045	Hepatic insulin sensitivity and IRS-2 levels play central roles in the pathogenesis of type 2 diabetes.
349	15983045	Socs1 deficiency increases IRS-2 expression and enhances hepatic insulin sensitivity in vivo indicating that inhibition of SOCS1 may be a logical strategy in type 2 diabetes.
350	15983045	Socs1 deficiency enhances hepatic insulin signaling.
351	15983045	In hyperinsulinemic clamp studies, however, Socs1-/- Ifng-/- mice had enhanced hepatic insulin sensitivity demonstrated by greater suppression of endogenous glucose production compared with controls with no difference in glucose disposal.
352	15983045	Socs1-/- Ifng-/- mice had elevated liver insulin receptor substrate 2 expression (IRS-2) and IRS-2 tyrosine phosphorylation.
353	15983045	Hepatic insulin sensitivity and IRS-2 levels play central roles in the pathogenesis of type 2 diabetes.
354	15983045	Socs1 deficiency increases IRS-2 expression and enhances hepatic insulin sensitivity in vivo indicating that inhibition of SOCS1 may be a logical strategy in type 2 diabetes.
355	16226915	Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome.
356	16226915	In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins.
357	16226915	Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1.
358	16226915	Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1.
359	16226915	Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3.
360	16226915	This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins.
361	16226915	Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins.
362	16226915	These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver.
363	16226915	Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling.
364	16226915	Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome.
365	16226915	In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins.
366	16226915	Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1.
367	16226915	Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1.
368	16226915	Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3.
369	16226915	This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins.
370	16226915	Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins.
371	16226915	These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver.
372	16226915	Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling.
373	16226915	Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome.
374	16226915	In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins.
375	16226915	Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1.
376	16226915	Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1.
377	16226915	Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3.
378	16226915	This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins.
379	16226915	Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins.
380	16226915	These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver.
381	16226915	Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling.
382	16226915	Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome.
383	16226915	In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins.
384	16226915	Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1.
385	16226915	Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1.
386	16226915	Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3.
387	16226915	This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins.
388	16226915	Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins.
389	16226915	These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver.
390	16226915	Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling.
391	16226915	Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome.
392	16226915	In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins.
393	16226915	Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1.
394	16226915	Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1.
395	16226915	Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3.
396	16226915	This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins.
397	16226915	Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins.
398	16226915	These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver.
399	16226915	Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling.
400	16426235	We first searched for polymorphisms in SOCS-1, SOCS-3 and SOCS-5 genes, and examined the association of the polymorphisms with type 1 diabetes (T1D).
401	16574667	Perforin and Fas induced by IFNgamma and TNFalpha mediate beta cell death by OT-I CTL.
402	16574667	It was also prevented by pre-incubation with anti-tumor necrosis factor-alpha (anti-TNFalpha) antibody or by blocking IFNgamma responsiveness through expressing a dominant negative IFNgamma receptor.
403	16574667	Perforin-deficient CTL produced IFNgamma and TNFalpha that was shown to directly induce islet Fas expression during the assays.
404	16574667	This suggests that Fas-deficiency, SOCS-1 overexpression and blockade of IFNgamma and TNFalpha all protect beta cells from residual cytotoxicity of perforin-deficient CTL by blocking Fas upregulation.
405	16574667	However, in the absence of perforin, the Fas/FasL pathway provides an alternative mechanism dependent on islet cell Fas upregulation by cytokines IFNgamma and TNFalpha.
406	16757551	Expression of the following signal proteins were assayed by Western blotting: STAT5/p-STAT5, MAPK, and Akt/PKB.
407	16757551	STAT5 DNA binding activity was assessed with EMSA, and the expression of IGF-I and SOCS mRNA was measured by real-time RT-PCR.
408	16757551	GH-induced STAT5 DNA binding and expression of IGF-I mRNA were detected in fat, whereas expression of SOCS-1 and -3 tended to increase after GH in muscle and fat, respectively.
409	16757551	We conclude that 1) STAT5 is acutely activated in human muscle and fat after a GH bolus, but additional downstream GH signaling was significant only in fat; 2) the direct GH effects in muscle need further characterization; and 3) this human in vivo model may be used to study the mechanisms subserving the actions of GH on substrate metabolism and insulin sensitivity in muscle and fat.
410	16936188	We have examined the contribution of perforin and Fas ligand to beta-cell destruction using islet-specific CD8(+) T-cells from T-cell receptor transgenic NOD8.3 mice.
411	16936188	Therefore, NOD8.3 T-cells use both perforin and Fas pathways to kill beta-cells and the surprising blockade of NOD8.3 T-cell-mediated beta-cell death by SOCS-1 overexpression may be due in part to reduced target cell recognition.
412	17010638	Attenuation of leptin and insulin signaling by SOCS proteins.
413	17010638	Leptin and insulin are key hormones involved in the regulation of energy balance and glucose homeostasis.
414	17010638	Specific members of the suppressor of cytokine signaling (SOCS) family of proteins are now thought to have a role in the development of leptin and insulin resistance owing to their ability to inhibit leptin and insulin signaling pathways.
415	17010638	In the case of leptin, current evidence suggests that SOCS3 appears to be of particular importance in the development of leptin resistance, whereas the ability to diminish insulin action has been described for several SOCS proteins (SOCS1, SOCS3, SOCS6 and SOCS7).
416	17045460	SOCS-1 protects from virally-induced CD8 T cell mediated type 1 diabetes.
417	17045460	CTL-mediated beta-cell killing can occur via perforin-mediated lysis, Fas-Fas-L interaction, and the secretion of TNF-alpha or IFN-gamma.
418	17045460	Suppressor of cytokine signaling-1 (SOCS-1) represses several crucial cytokine signaling pathways simultaneously, among them IFN-gamma and IL-1-beta.
419	17045460	We therefore evaluated the protective capacity of islet cell SOCS-1 expression in the CD8(+) mediated RIP-LCMV diabetes model.
420	17045460	Not only absence of MHC-I and Fas upregulation, but also resistance to cytokine-induced killing of beta-cells and a complete lack of CXCL-10 (IP10) production in islets led to a lack of islet infiltration and impaired activation of autoaggressive CD4(+) and CD8(+) T-cells in these mice.
421	17045460	SOCS-1 protects from virally-induced CD8 T cell mediated type 1 diabetes.
422	17045460	CTL-mediated beta-cell killing can occur via perforin-mediated lysis, Fas-Fas-L interaction, and the secretion of TNF-alpha or IFN-gamma.
423	17045460	Suppressor of cytokine signaling-1 (SOCS-1) represses several crucial cytokine signaling pathways simultaneously, among them IFN-gamma and IL-1-beta.
424	17045460	We therefore evaluated the protective capacity of islet cell SOCS-1 expression in the CD8(+) mediated RIP-LCMV diabetes model.
425	17045460	Not only absence of MHC-I and Fas upregulation, but also resistance to cytokine-induced killing of beta-cells and a complete lack of CXCL-10 (IP10) production in islets led to a lack of islet infiltration and impaired activation of autoaggressive CD4(+) and CD8(+) T-cells in these mice.
426	17045460	SOCS-1 protects from virally-induced CD8 T cell mediated type 1 diabetes.
427	17045460	CTL-mediated beta-cell killing can occur via perforin-mediated lysis, Fas-Fas-L interaction, and the secretion of TNF-alpha or IFN-gamma.
428	17045460	Suppressor of cytokine signaling-1 (SOCS-1) represses several crucial cytokine signaling pathways simultaneously, among them IFN-gamma and IL-1-beta.
429	17045460	We therefore evaluated the protective capacity of islet cell SOCS-1 expression in the CD8(+) mediated RIP-LCMV diabetes model.
430	17045460	Not only absence of MHC-I and Fas upregulation, but also resistance to cytokine-induced killing of beta-cells and a complete lack of CXCL-10 (IP10) production in islets led to a lack of islet infiltration and impaired activation of autoaggressive CD4(+) and CD8(+) T-cells in these mice.
431	18171427	SOCS proteins causing trouble in insulin action.
432	18171427	SOCS-1 and SOCS-3 have been extensively studied both in vitro and in vivo in the context of insulin action.
433	18171427	It has been shown that these two SOCS members are able to inhibit the insulin signalling pathway by three different mechanisms: (1) inhibition of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins because of competition at the docking site on the insulin receptor (IR), (2) induction of the proteasomal degradation of the IRS and (3) inhibition of the IR kinase.
434	18171427	A significant correlation between SOCS-3 expression and insulin resistance has been demonstrated in vivo.
435	18171427	Interestingly, the level of SOCS-3 expression is strikingly enhanced in insulin-sensitive tissues from both patients and animal models with type 2 diabetes and insulin resistance.
436	18171427	While it remains to be established whether the increased expression of SOCS is a cause or a consequence of insulin resistance, a large body of observations supports a role for SOCS proteins in the disease process found in states with insulin resistance.
437	18171911	HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus.
438	18171911	Oligonucleotide gene array analyses revealed upregulation of suppressor of cytokine signaling-1 (SOCS-1) expression in insulin-sensitive tissues of IDV rats.
439	18171911	SOCS-1 is a known inducer of insulin resistance and diabetes, and immunoblotting analyses revealed increases in SOCS-1 protein expression in adipose, skeletal muscle, and liver tissues of IDV-administered ZDF rats.
440	18171911	This was associated with increases in the upstream regulator TNF-alpha and downstream effector sterol regulatory element-binding protein-1 and a decrease in IRS-2.
441	18171911	HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus.
442	18171911	Oligonucleotide gene array analyses revealed upregulation of suppressor of cytokine signaling-1 (SOCS-1) expression in insulin-sensitive tissues of IDV rats.
443	18171911	SOCS-1 is a known inducer of insulin resistance and diabetes, and immunoblotting analyses revealed increases in SOCS-1 protein expression in adipose, skeletal muscle, and liver tissues of IDV-administered ZDF rats.
444	18171911	This was associated with increases in the upstream regulator TNF-alpha and downstream effector sterol regulatory element-binding protein-1 and a decrease in IRS-2.
445	18171911	HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus.
446	18171911	Oligonucleotide gene array analyses revealed upregulation of suppressor of cytokine signaling-1 (SOCS-1) expression in insulin-sensitive tissues of IDV rats.
447	18171911	SOCS-1 is a known inducer of insulin resistance and diabetes, and immunoblotting analyses revealed increases in SOCS-1 protein expression in adipose, skeletal muscle, and liver tissues of IDV-administered ZDF rats.
448	18171911	This was associated with increases in the upstream regulator TNF-alpha and downstream effector sterol regulatory element-binding protein-1 and a decrease in IRS-2.
449	18585970	Recent research revealed several molecules, including tumor necrosis factor alpha, suppressor of cytokine signaling 1 and 3 proteins, insulin-receptor substrates 1 and 2, and other adipocytokines, potentially are involved in the development of insulin resistance in patients with chronic hepatitis C.
450	18929539	SOCS-1 deficiency does not prevent diet-induced insulin resistance.
451	18929539	Obesity is associated with inflammation and increased expression of suppressor of cytokine signaling (SOCS) proteins, which inhibit cytokine and insulin signaling.
452	18929539	Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance.
453	18929539	Using SOCS-1 knockout mice, we investigated the contribution of SOCS-1 in the development of insulin resistance induced by a high-fat diet (HFD).
454	18929539	This was accompanied by increased mRNA expression of leptin and the macrophage marker CD68 in white adipose tissue and of SREBP1c and FAS in liver.
455	18929539	HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests.
456	18929539	Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency alone is not able to prevent insulin resistance induced by a diet rich in fat.
457	18929539	SOCS-1 deficiency does not prevent diet-induced insulin resistance.
458	18929539	Obesity is associated with inflammation and increased expression of suppressor of cytokine signaling (SOCS) proteins, which inhibit cytokine and insulin signaling.
459	18929539	Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance.
460	18929539	Using SOCS-1 knockout mice, we investigated the contribution of SOCS-1 in the development of insulin resistance induced by a high-fat diet (HFD).
461	18929539	This was accompanied by increased mRNA expression of leptin and the macrophage marker CD68 in white adipose tissue and of SREBP1c and FAS in liver.
462	18929539	HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests.
463	18929539	Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency alone is not able to prevent insulin resistance induced by a diet rich in fat.
464	18929539	SOCS-1 deficiency does not prevent diet-induced insulin resistance.
465	18929539	Obesity is associated with inflammation and increased expression of suppressor of cytokine signaling (SOCS) proteins, which inhibit cytokine and insulin signaling.
466	18929539	Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance.
467	18929539	Using SOCS-1 knockout mice, we investigated the contribution of SOCS-1 in the development of insulin resistance induced by a high-fat diet (HFD).
468	18929539	This was accompanied by increased mRNA expression of leptin and the macrophage marker CD68 in white adipose tissue and of SREBP1c and FAS in liver.
469	18929539	HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests.
470	18929539	Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency alone is not able to prevent insulin resistance induced by a diet rich in fat.
471	18929539	SOCS-1 deficiency does not prevent diet-induced insulin resistance.
472	18929539	Obesity is associated with inflammation and increased expression of suppressor of cytokine signaling (SOCS) proteins, which inhibit cytokine and insulin signaling.
473	18929539	Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance.
474	18929539	Using SOCS-1 knockout mice, we investigated the contribution of SOCS-1 in the development of insulin resistance induced by a high-fat diet (HFD).
475	18929539	This was accompanied by increased mRNA expression of leptin and the macrophage marker CD68 in white adipose tissue and of SREBP1c and FAS in liver.
476	18929539	HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests.
477	18929539	Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency alone is not able to prevent insulin resistance induced by a diet rich in fat.
478	19008912	Insulin regulates SOCS2 expression and the mitogenic effect of IGF-1 in mesangial cells.
479	19008912	Using DNA microarray analysis of glomerular RNA from control and diabetic rats we found that the expression levels of insulin-like growth factor 1 receptor (IGF-1R) were increased while those of suppressor of cytokine signaling 2 (SOCS2) and STAT5 were decreased.
480	19008912	Overexpression of SOCS2 in rat mesangial cells inhibited IGF-1-induced activation of extracellular signal-regulated kinase, which subsequently reduced type IV collagen and DNA synthesis, an effect due to interaction of SOCS2 with IGF-1R.
481	19008912	Inhibition of SOCS2 overexpression by small interfering RNA suppressed IGF-1R-mediated actions by preventing phosphorylation of tyrosine 317 in the p66Shc adaptor protein; however, overexpression of either SOCS1 or SOCS3 did not affect IGF-1R signaling.
482	19008912	Insulin directly increased STAT5 and SOCS2 expression in mesangial cells.
483	19008912	This study shows that insulin can inhibit the mitogenic action of IGF-1 in mesangial cells by regulating STAT5/SOCS2 expression.
484	19008912	Insulin deficiency may contribute to the mesangial expansion found in diabetes through reduced STAT5/SOCS2 expression.
485	19177839	We studied the expression of a set of selected genes involved in apoptosis (Bcl2, Bclx(L), Bax, Bad, Bid, and CHOP), cytokine defense, (SOCS-1 and SOCS-3), or free radical protection (Hmox1, Cu/Zn-SOD, Mn-SOD, and Hsp70).
486	19177839	The expression of proapoptotic genes Bid and CHOP, as well as protective genes Bclx(L), Socs1, Socs3, Hmox1, and MnSod, was maximally increased 1 day after transplantation, and in most cases it remained increased 7 days later, indicating the presence of a protective response against cell damage.
487	19177839	In contrast, the expression of Bcl2, Bax, Bad, Cu/ZnSod, and Hsp70 genes did not change.
488	19177839	We studied the expression of a set of selected genes involved in apoptosis (Bcl2, Bclx(L), Bax, Bad, Bid, and CHOP), cytokine defense, (SOCS-1 and SOCS-3), or free radical protection (Hmox1, Cu/Zn-SOD, Mn-SOD, and Hsp70).
489	19177839	The expression of proapoptotic genes Bid and CHOP, as well as protective genes Bclx(L), Socs1, Socs3, Hmox1, and MnSod, was maximally increased 1 day after transplantation, and in most cases it remained increased 7 days later, indicating the presence of a protective response against cell damage.
490	19177839	In contrast, the expression of Bcl2, Bax, Bad, Cu/ZnSod, and Hsp70 genes did not change.
491	19414010	JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway.
492	19414010	The molecular mechanism by which JANEX-1 inhibits iNOS expression was mediated through suppression of the nuclear factor kappaB (NF-kappaB) and JAK/signal transducer and activator of transcription (STAT) pathways.
493	19414010	Islets treated with the cytokines downregulated the protein levels of suppressor of cytokine signaling (SOCS)-1 and SOCS-3, but pretreatment with JANEX-1 attenuated these decreases.
494	19414010	These results demonstrate that JANEX-1 protects beta-cells from cytokine toxicity through suppression of the NF-kappaB and JAK/STAT pathways and upregulation of SOCS proteins, suggesting that JANEX-1 may be used to preserve functional beta-cell mass.
495	19587264	The translocation and localization of glucose transporter 4 (GLUT4) to the adipocyte plasma membrane were impaired in TH mice compared to control C57BL6/J (B6) mice.
496	19587264	These defects were associated with decreased GLUT4 protein, reduced phosphatidylinositol 3-kinase activity, and alterations in the phosphorylation status of insulin receptor substrate 1 (IRS1).
497	19587264	Activation of c-Jun N-terminal kinase 1/2, which can phosphorylate IRS1 on Ser307, was significantly higher in TH mice compared with B6 controls.
498	19587264	Immunoprecipitation with anti-ubiquitin and western blot analysis of IRS1 protein revealed increased total IRS1 ubiquitination in adipose tissue of TH mice.
499	19587264	Suppressor of cytokine signaling 1, known to promote IRS1 ubiquitination and subsequent degradation, was found at significantly higher levels in TH mice compared with B6.
500	19587264	Our findings suggest that increased IRS1 degradation and subsequent impaired GLUT4 mobilization play a role in the reduced glucose uptake in insulin resistant TH mice.
501	19763396	Pancreatic beta cell damage caused by proinflammatory cytokines interleukin-1beta (IL-1beta), interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha) is a key event in the pathogenesis of type 1 diabetes.
502	19763396	The suppressor of cytokine signaling-1 (SOCS-1) blocks IFNgamma-induced signaling and prevents diabetes in the non-obese diabetic mouse.
503	19763396	We demonstrate that SOCS-1 does not prevent increase in NO production and decrease in glucose-stimulated insulin secretion in the presence of IL-1beta, IFNgamma, TNFalpha.
504	19763396	Our data suggest that SOCS-1 overexpression may not be sufficient in preventing all the biological activities of IFNgamma in beta cells.
505	19763396	In summary, we show that interference with IFNgamma signal transduction pathways by SOCS-1 inhibits cytokine-stimulated pancreatic beta cell death.
506	19763396	Pancreatic beta cell damage caused by proinflammatory cytokines interleukin-1beta (IL-1beta), interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha) is a key event in the pathogenesis of type 1 diabetes.
507	19763396	The suppressor of cytokine signaling-1 (SOCS-1) blocks IFNgamma-induced signaling and prevents diabetes in the non-obese diabetic mouse.
508	19763396	We demonstrate that SOCS-1 does not prevent increase in NO production and decrease in glucose-stimulated insulin secretion in the presence of IL-1beta, IFNgamma, TNFalpha.
509	19763396	Our data suggest that SOCS-1 overexpression may not be sufficient in preventing all the biological activities of IFNgamma in beta cells.
510	19763396	In summary, we show that interference with IFNgamma signal transduction pathways by SOCS-1 inhibits cytokine-stimulated pancreatic beta cell death.
511	19763396	Pancreatic beta cell damage caused by proinflammatory cytokines interleukin-1beta (IL-1beta), interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha) is a key event in the pathogenesis of type 1 diabetes.
512	19763396	The suppressor of cytokine signaling-1 (SOCS-1) blocks IFNgamma-induced signaling and prevents diabetes in the non-obese diabetic mouse.
513	19763396	We demonstrate that SOCS-1 does not prevent increase in NO production and decrease in glucose-stimulated insulin secretion in the presence of IL-1beta, IFNgamma, TNFalpha.
514	19763396	Our data suggest that SOCS-1 overexpression may not be sufficient in preventing all the biological activities of IFNgamma in beta cells.
515	19763396	In summary, we show that interference with IFNgamma signal transduction pathways by SOCS-1 inhibits cytokine-stimulated pancreatic beta cell death.
516	19763396	Pancreatic beta cell damage caused by proinflammatory cytokines interleukin-1beta (IL-1beta), interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha) is a key event in the pathogenesis of type 1 diabetes.
517	19763396	The suppressor of cytokine signaling-1 (SOCS-1) blocks IFNgamma-induced signaling and prevents diabetes in the non-obese diabetic mouse.
518	19763396	We demonstrate that SOCS-1 does not prevent increase in NO production and decrease in glucose-stimulated insulin secretion in the presence of IL-1beta, IFNgamma, TNFalpha.
519	19763396	Our data suggest that SOCS-1 overexpression may not be sufficient in preventing all the biological activities of IFNgamma in beta cells.
520	19763396	In summary, we show that interference with IFNgamma signal transduction pathways by SOCS-1 inhibits cytokine-stimulated pancreatic beta cell death.
521	20067833	High glucose induces suppression of insulin signalling and apoptosis via upregulation of endogenous IL-1beta and suppressor of cytokine signalling-1 in mouse pancreatic beta cells.
522	20067833	Suppressors of cytokine signalling (SOCS) were induced by several cytokines and inhibit insulin-initiated signal transduction.
523	20067833	The aim of this study was to investigate whether high glucose can influence endogenous interleukin-1beta (IL-1beta) and SOCS expression thus affecting insulin signalling and survival in insulin-producing mouse pancreatic beta cells (betaTC-6).
524	20067833	Results showed that prolonged exposure of betaTC-6 cells to increased glucose concentrations resulted in significant inhibition of insulin-induced tyrosine phosphorylation of the insulin receptor (IR), and insulin receptor substrate-2 (IRS-2) as well as PI3-kinase activation.
525	20067833	Glucose-induced attenuation of IRS-2/Akt-mediated signalling was associated with increased IL-1beta expression.
526	20067833	Enhanced endogenous IL-1beta specifically induced mRNA and protein expression of SOCS-1 in betaTC-6 cells.
527	20067833	Inhibition of SOCS-1 expression by SOCS-1-specific small interfering RNA restored IRS-2/PI3K-mediated Akt phosphorylation suppressed by high glucose.
528	20067833	These results indicated that glucose-induced endogenous IL-1beta expression increased betaTC-6 cells apoptosis by inhibiting, at least in part, IRS-2/Akt-mediated signalling through SOCS-1 upregulation.
529	20067833	High glucose induces suppression of insulin signalling and apoptosis via upregulation of endogenous IL-1beta and suppressor of cytokine signalling-1 in mouse pancreatic beta cells.
530	20067833	Suppressors of cytokine signalling (SOCS) were induced by several cytokines and inhibit insulin-initiated signal transduction.
531	20067833	The aim of this study was to investigate whether high glucose can influence endogenous interleukin-1beta (IL-1beta) and SOCS expression thus affecting insulin signalling and survival in insulin-producing mouse pancreatic beta cells (betaTC-6).
532	20067833	Results showed that prolonged exposure of betaTC-6 cells to increased glucose concentrations resulted in significant inhibition of insulin-induced tyrosine phosphorylation of the insulin receptor (IR), and insulin receptor substrate-2 (IRS-2) as well as PI3-kinase activation.
533	20067833	Glucose-induced attenuation of IRS-2/Akt-mediated signalling was associated with increased IL-1beta expression.
534	20067833	Enhanced endogenous IL-1beta specifically induced mRNA and protein expression of SOCS-1 in betaTC-6 cells.
535	20067833	Inhibition of SOCS-1 expression by SOCS-1-specific small interfering RNA restored IRS-2/PI3K-mediated Akt phosphorylation suppressed by high glucose.
536	20067833	These results indicated that glucose-induced endogenous IL-1beta expression increased betaTC-6 cells apoptosis by inhibiting, at least in part, IRS-2/Akt-mediated signalling through SOCS-1 upregulation.
537	20067833	High glucose induces suppression of insulin signalling and apoptosis via upregulation of endogenous IL-1beta and suppressor of cytokine signalling-1 in mouse pancreatic beta cells.
538	20067833	Suppressors of cytokine signalling (SOCS) were induced by several cytokines and inhibit insulin-initiated signal transduction.
539	20067833	The aim of this study was to investigate whether high glucose can influence endogenous interleukin-1beta (IL-1beta) and SOCS expression thus affecting insulin signalling and survival in insulin-producing mouse pancreatic beta cells (betaTC-6).
540	20067833	Results showed that prolonged exposure of betaTC-6 cells to increased glucose concentrations resulted in significant inhibition of insulin-induced tyrosine phosphorylation of the insulin receptor (IR), and insulin receptor substrate-2 (IRS-2) as well as PI3-kinase activation.
541	20067833	Glucose-induced attenuation of IRS-2/Akt-mediated signalling was associated with increased IL-1beta expression.
542	20067833	Enhanced endogenous IL-1beta specifically induced mRNA and protein expression of SOCS-1 in betaTC-6 cells.
543	20067833	Inhibition of SOCS-1 expression by SOCS-1-specific small interfering RNA restored IRS-2/PI3K-mediated Akt phosphorylation suppressed by high glucose.
544	20067833	These results indicated that glucose-induced endogenous IL-1beta expression increased betaTC-6 cells apoptosis by inhibiting, at least in part, IRS-2/Akt-mediated signalling through SOCS-1 upregulation.
545	20299783	Suppressor of cytokine signaling-1 ameliorates expression of MCP-1 in diabetic nephropathy.
546	20437361	In particular, cardiac genes that modulate the oxidative stress response or the stress induced by pro-inflammatory cytokines (p66Shc, SOCS-1, SOCS-3) were analyzed.
547	20519645	Regulation of cytokine-driven functional differentiation of CD8 T cells by suppressor of cytokine signaling 1 controls autoimmunity and preserves their proliferative capacity toward foreign antigens.
548	20519645	We have previously shown that naive CD8 T cells exposed to IL-7 or IL-15 in the presence of IL-21 undergo Ag-independent proliferation with concomitant increase in TCR sensitivity.
549	20519645	In this study, we examined whether CD8 T cells that accumulate in suppressor of cytokine signaling 1 (SOCS1)-deficient mice because of increased IL-15 signaling in vivo would respond to an autoantigen expressed at a very low level using a mouse model of autoimmune diabetes.
550	20519645	In this model, P14 TCR transgenic CD8 T cells (P14 cells) adoptively transferred to rat insulin promoter-glycoprotein (RIP-GP) mice, which express the cognate Ag in the islets, do not induce diabetes unless the donor cells are stimulated by exogenous Ag.
551	20519645	Surprisingly, SOCS1-deficient P14 cells, which expanded robustly following IL-15 stimulation, proliferated poorly in response to Ag and failed to cause diabetes in RIP-GP mice.
552	20519645	SOCS1-deficient CD8 T cells expressing a polyclonal TCR repertoire also showed defective expansion following in vivo Ag stimulation.
553	20519645	Notwithstanding the Ag-specific proliferation defect, SOCS1-null P14 cells produced IFN-gamma and displayed potent cytolytic activity upon Ag stimulation, suggesting that SOCS1-null CD8 T cells underwent cytokine-driven functional differentiation that selectively compromised their proliferative response to Ag but not to cytokines.
554	20519645	These findings suggest that by attenuating cytokine-driven proliferation and functional differentiation, SOCS1 not only controls the pathogenicity of autoreactive cells but also preserves the ability of CD8 T cells to proliferate in response to Ags.
555	20519645	Regulation of cytokine-driven functional differentiation of CD8 T cells by suppressor of cytokine signaling 1 controls autoimmunity and preserves their proliferative capacity toward foreign antigens.
556	20519645	We have previously shown that naive CD8 T cells exposed to IL-7 or IL-15 in the presence of IL-21 undergo Ag-independent proliferation with concomitant increase in TCR sensitivity.
557	20519645	In this study, we examined whether CD8 T cells that accumulate in suppressor of cytokine signaling 1 (SOCS1)-deficient mice because of increased IL-15 signaling in vivo would respond to an autoantigen expressed at a very low level using a mouse model of autoimmune diabetes.
558	20519645	In this model, P14 TCR transgenic CD8 T cells (P14 cells) adoptively transferred to rat insulin promoter-glycoprotein (RIP-GP) mice, which express the cognate Ag in the islets, do not induce diabetes unless the donor cells are stimulated by exogenous Ag.
559	20519645	Surprisingly, SOCS1-deficient P14 cells, which expanded robustly following IL-15 stimulation, proliferated poorly in response to Ag and failed to cause diabetes in RIP-GP mice.
560	20519645	SOCS1-deficient CD8 T cells expressing a polyclonal TCR repertoire also showed defective expansion following in vivo Ag stimulation.
561	20519645	Notwithstanding the Ag-specific proliferation defect, SOCS1-null P14 cells produced IFN-gamma and displayed potent cytolytic activity upon Ag stimulation, suggesting that SOCS1-null CD8 T cells underwent cytokine-driven functional differentiation that selectively compromised their proliferative response to Ag but not to cytokines.
562	20519645	These findings suggest that by attenuating cytokine-driven proliferation and functional differentiation, SOCS1 not only controls the pathogenicity of autoreactive cells but also preserves the ability of CD8 T cells to proliferate in response to Ags.
563	20519645	Regulation of cytokine-driven functional differentiation of CD8 T cells by suppressor of cytokine signaling 1 controls autoimmunity and preserves their proliferative capacity toward foreign antigens.
564	20519645	We have previously shown that naive CD8 T cells exposed to IL-7 or IL-15 in the presence of IL-21 undergo Ag-independent proliferation with concomitant increase in TCR sensitivity.
565	20519645	In this study, we examined whether CD8 T cells that accumulate in suppressor of cytokine signaling 1 (SOCS1)-deficient mice because of increased IL-15 signaling in vivo would respond to an autoantigen expressed at a very low level using a mouse model of autoimmune diabetes.
566	20519645	In this model, P14 TCR transgenic CD8 T cells (P14 cells) adoptively transferred to rat insulin promoter-glycoprotein (RIP-GP) mice, which express the cognate Ag in the islets, do not induce diabetes unless the donor cells are stimulated by exogenous Ag.
567	20519645	Surprisingly, SOCS1-deficient P14 cells, which expanded robustly following IL-15 stimulation, proliferated poorly in response to Ag and failed to cause diabetes in RIP-GP mice.
568	20519645	SOCS1-deficient CD8 T cells expressing a polyclonal TCR repertoire also showed defective expansion following in vivo Ag stimulation.
569	20519645	Notwithstanding the Ag-specific proliferation defect, SOCS1-null P14 cells produced IFN-gamma and displayed potent cytolytic activity upon Ag stimulation, suggesting that SOCS1-null CD8 T cells underwent cytokine-driven functional differentiation that selectively compromised their proliferative response to Ag but not to cytokines.
570	20519645	These findings suggest that by attenuating cytokine-driven proliferation and functional differentiation, SOCS1 not only controls the pathogenicity of autoreactive cells but also preserves the ability of CD8 T cells to proliferate in response to Ags.
571	20519645	Regulation of cytokine-driven functional differentiation of CD8 T cells by suppressor of cytokine signaling 1 controls autoimmunity and preserves their proliferative capacity toward foreign antigens.
572	20519645	We have previously shown that naive CD8 T cells exposed to IL-7 or IL-15 in the presence of IL-21 undergo Ag-independent proliferation with concomitant increase in TCR sensitivity.
573	20519645	In this study, we examined whether CD8 T cells that accumulate in suppressor of cytokine signaling 1 (SOCS1)-deficient mice because of increased IL-15 signaling in vivo would respond to an autoantigen expressed at a very low level using a mouse model of autoimmune diabetes.
574	20519645	In this model, P14 TCR transgenic CD8 T cells (P14 cells) adoptively transferred to rat insulin promoter-glycoprotein (RIP-GP) mice, which express the cognate Ag in the islets, do not induce diabetes unless the donor cells are stimulated by exogenous Ag.
575	20519645	Surprisingly, SOCS1-deficient P14 cells, which expanded robustly following IL-15 stimulation, proliferated poorly in response to Ag and failed to cause diabetes in RIP-GP mice.
576	20519645	SOCS1-deficient CD8 T cells expressing a polyclonal TCR repertoire also showed defective expansion following in vivo Ag stimulation.
577	20519645	Notwithstanding the Ag-specific proliferation defect, SOCS1-null P14 cells produced IFN-gamma and displayed potent cytolytic activity upon Ag stimulation, suggesting that SOCS1-null CD8 T cells underwent cytokine-driven functional differentiation that selectively compromised their proliferative response to Ag but not to cytokines.
578	20519645	These findings suggest that by attenuating cytokine-driven proliferation and functional differentiation, SOCS1 not only controls the pathogenicity of autoreactive cells but also preserves the ability of CD8 T cells to proliferate in response to Ags.
579	20519645	Regulation of cytokine-driven functional differentiation of CD8 T cells by suppressor of cytokine signaling 1 controls autoimmunity and preserves their proliferative capacity toward foreign antigens.
580	20519645	We have previously shown that naive CD8 T cells exposed to IL-7 or IL-15 in the presence of IL-21 undergo Ag-independent proliferation with concomitant increase in TCR sensitivity.
581	20519645	In this study, we examined whether CD8 T cells that accumulate in suppressor of cytokine signaling 1 (SOCS1)-deficient mice because of increased IL-15 signaling in vivo would respond to an autoantigen expressed at a very low level using a mouse model of autoimmune diabetes.
582	20519645	In this model, P14 TCR transgenic CD8 T cells (P14 cells) adoptively transferred to rat insulin promoter-glycoprotein (RIP-GP) mice, which express the cognate Ag in the islets, do not induce diabetes unless the donor cells are stimulated by exogenous Ag.
583	20519645	Surprisingly, SOCS1-deficient P14 cells, which expanded robustly following IL-15 stimulation, proliferated poorly in response to Ag and failed to cause diabetes in RIP-GP mice.
584	20519645	SOCS1-deficient CD8 T cells expressing a polyclonal TCR repertoire also showed defective expansion following in vivo Ag stimulation.
585	20519645	Notwithstanding the Ag-specific proliferation defect, SOCS1-null P14 cells produced IFN-gamma and displayed potent cytolytic activity upon Ag stimulation, suggesting that SOCS1-null CD8 T cells underwent cytokine-driven functional differentiation that selectively compromised their proliferative response to Ag but not to cytokines.
586	20519645	These findings suggest that by attenuating cytokine-driven proliferation and functional differentiation, SOCS1 not only controls the pathogenicity of autoreactive cells but also preserves the ability of CD8 T cells to proliferate in response to Ags.
587	20519645	Regulation of cytokine-driven functional differentiation of CD8 T cells by suppressor of cytokine signaling 1 controls autoimmunity and preserves their proliferative capacity toward foreign antigens.
588	20519645	We have previously shown that naive CD8 T cells exposed to IL-7 or IL-15 in the presence of IL-21 undergo Ag-independent proliferation with concomitant increase in TCR sensitivity.
589	20519645	In this study, we examined whether CD8 T cells that accumulate in suppressor of cytokine signaling 1 (SOCS1)-deficient mice because of increased IL-15 signaling in vivo would respond to an autoantigen expressed at a very low level using a mouse model of autoimmune diabetes.
590	20519645	In this model, P14 TCR transgenic CD8 T cells (P14 cells) adoptively transferred to rat insulin promoter-glycoprotein (RIP-GP) mice, which express the cognate Ag in the islets, do not induce diabetes unless the donor cells are stimulated by exogenous Ag.
591	20519645	Surprisingly, SOCS1-deficient P14 cells, which expanded robustly following IL-15 stimulation, proliferated poorly in response to Ag and failed to cause diabetes in RIP-GP mice.
592	20519645	SOCS1-deficient CD8 T cells expressing a polyclonal TCR repertoire also showed defective expansion following in vivo Ag stimulation.
593	20519645	Notwithstanding the Ag-specific proliferation defect, SOCS1-null P14 cells produced IFN-gamma and displayed potent cytolytic activity upon Ag stimulation, suggesting that SOCS1-null CD8 T cells underwent cytokine-driven functional differentiation that selectively compromised their proliferative response to Ag but not to cytokines.
594	20519645	These findings suggest that by attenuating cytokine-driven proliferation and functional differentiation, SOCS1 not only controls the pathogenicity of autoreactive cells but also preserves the ability of CD8 T cells to proliferate in response to Ags.
595	21099320	No non-redundant function of suppressor of cytokine signaling 2 in insulin producing β-cells.
596	21099320	The members of the Suppressor of Cytokine Signaling (SOCS) protein family mainly modulate the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway.
597	21099320	SOCS-1 and SOCS-3 have already been shown to influence growth and apoptosis of pancreatic beta cells.
598	21099320	We found that SOCS-2-/- mice have normal islet insulin secretion and unchanged glucose and insulin tolerance compared to wildtype controls.
599	21099320	Interleukin-1β mediated cell death in vitro was unchanged after SOCS-2 knockdown.
600	21099320	In summary, SOCS-2-/- knockout mice have a normal function of insulin-producing pancreatic β-cells, a fully adapted beta cell mass and a normal morphology of the endocrine islets.
601	22522613	Amyloid-β induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway.
602	22522613	Aβ can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor.
603	22522613	Knockdown of SOCS-1 alleviates Aβ-induced impairment of insulin signaling.
604	22522613	Moreover, JAK2/STAT3 is activated by Aβ, and inhibition of JAK2/STAT3 signaling attenuates Aβ-induced upregulation of SOCS-1 and insulin resistance in hepatocytes.
605	22522613	Our results demonstrate that Aβ induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM.
606	22522613	Amyloid-β induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway.
607	22522613	Aβ can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor.
608	22522613	Knockdown of SOCS-1 alleviates Aβ-induced impairment of insulin signaling.
609	22522613	Moreover, JAK2/STAT3 is activated by Aβ, and inhibition of JAK2/STAT3 signaling attenuates Aβ-induced upregulation of SOCS-1 and insulin resistance in hepatocytes.
610	22522613	Our results demonstrate that Aβ induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM.
611	22522613	Amyloid-β induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway.
612	22522613	Aβ can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor.
613	22522613	Knockdown of SOCS-1 alleviates Aβ-induced impairment of insulin signaling.
614	22522613	Moreover, JAK2/STAT3 is activated by Aβ, and inhibition of JAK2/STAT3 signaling attenuates Aβ-induced upregulation of SOCS-1 and insulin resistance in hepatocytes.
615	22522613	Our results demonstrate that Aβ induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM.
616	22522613	Amyloid-β induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway.
617	22522613	Aβ can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor.
618	22522613	Knockdown of SOCS-1 alleviates Aβ-induced impairment of insulin signaling.
619	22522613	Moreover, JAK2/STAT3 is activated by Aβ, and inhibition of JAK2/STAT3 signaling attenuates Aβ-induced upregulation of SOCS-1 and insulin resistance in hepatocytes.
620	22522613	Our results demonstrate that Aβ induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM.
621	22522613	Amyloid-β induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway.
622	22522613	Aβ can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor.
623	22522613	Knockdown of SOCS-1 alleviates Aβ-induced impairment of insulin signaling.
624	22522613	Moreover, JAK2/STAT3 is activated by Aβ, and inhibition of JAK2/STAT3 signaling attenuates Aβ-induced upregulation of SOCS-1 and insulin resistance in hepatocytes.
625	22522613	Our results demonstrate that Aβ induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM.
626	23024779	Alveolar macrophages (AMs) were cultured in vitro for analysis of IκB and p65 subunit of NFκB phosphorylation and MyD88 and SOCS-1 mRNA.
627	23024779	Moreover, in AMs from diabetic rats the expression of MyD88 mRNA was lower and that of SOCS-1 mRNA was increased compared with AMs from non-diabetic rats.
628	23024779	These results show that ALI secondary to sepsis is milder in diabetic rats and this correlates with impaired activation of NFκB, increased SOCS-1 and decreased MyD88 mRNA.
629	23024779	Alveolar macrophages (AMs) were cultured in vitro for analysis of IκB and p65 subunit of NFκB phosphorylation and MyD88 and SOCS-1 mRNA.
630	23024779	Moreover, in AMs from diabetic rats the expression of MyD88 mRNA was lower and that of SOCS-1 mRNA was increased compared with AMs from non-diabetic rats.
631	23024779	These results show that ALI secondary to sepsis is milder in diabetic rats and this correlates with impaired activation of NFκB, increased SOCS-1 and decreased MyD88 mRNA.
632	23024779	Alveolar macrophages (AMs) were cultured in vitro for analysis of IκB and p65 subunit of NFκB phosphorylation and MyD88 and SOCS-1 mRNA.
633	23024779	Moreover, in AMs from diabetic rats the expression of MyD88 mRNA was lower and that of SOCS-1 mRNA was increased compared with AMs from non-diabetic rats.
634	23024779	These results show that ALI secondary to sepsis is milder in diabetic rats and this correlates with impaired activation of NFκB, increased SOCS-1 and decreased MyD88 mRNA.
635	23149823	These were accompanied by overexpression of negative regulators of NFκB, TLR, and other proinflammatory pathways, e.g., A20, SOCS1, IRAK-M, IκBα, Triad3A, Tollip, SIGIRR, and ST2L.
636	23149823	Anti-inflammatory and immunomodulatory molecules, e.g., IL-10, IL-4, and TSLP that favor TH2 responses were strongly induced.
637	23223021	Amyloid-β induces hepatic insulin resistance in vivo via JAK2.
638	23223021	Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway.
639	23223021	Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin tolerance and hepatic insulin resistance.
640	23223021	Injection of Aβ42 activates hepatic JAK2/STAT3/SOCS-1 signaling, and neutralization of Aβ in APPswe/PSEN1dE9 mice inhibits liver JAK2/STAT3/SOCS-1 signaling.
641	23223021	Furthermore, knockdown of hepatic JAK2 by tail vein injection of adenovirus inhibits JAK2/STAT3/SOCS-1 signaling and improves glucose/insulin tolerance and hepatic insulin sensitivity in APPswe/PSEN1dE9 mice.
642	23223021	Our results demonstrate that Aβ induces hepatic insulin resistance in vivo via JAK2, suggesting that inhibition of Aβ signaling is a new strategy toward resolving insulin resistance and T2DM.
643	23223021	Amyloid-β induces hepatic insulin resistance in vivo via JAK2.
644	23223021	Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway.
645	23223021	Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin tolerance and hepatic insulin resistance.
646	23223021	Injection of Aβ42 activates hepatic JAK2/STAT3/SOCS-1 signaling, and neutralization of Aβ in APPswe/PSEN1dE9 mice inhibits liver JAK2/STAT3/SOCS-1 signaling.
647	23223021	Furthermore, knockdown of hepatic JAK2 by tail vein injection of adenovirus inhibits JAK2/STAT3/SOCS-1 signaling and improves glucose/insulin tolerance and hepatic insulin sensitivity in APPswe/PSEN1dE9 mice.
648	23223021	Our results demonstrate that Aβ induces hepatic insulin resistance in vivo via JAK2, suggesting that inhibition of Aβ signaling is a new strategy toward resolving insulin resistance and T2DM.
649	23223021	Amyloid-β induces hepatic insulin resistance in vivo via JAK2.
650	23223021	Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway.
651	23223021	Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin tolerance and hepatic insulin resistance.
652	23223021	Injection of Aβ42 activates hepatic JAK2/STAT3/SOCS-1 signaling, and neutralization of Aβ in APPswe/PSEN1dE9 mice inhibits liver JAK2/STAT3/SOCS-1 signaling.
653	23223021	Furthermore, knockdown of hepatic JAK2 by tail vein injection of adenovirus inhibits JAK2/STAT3/SOCS-1 signaling and improves glucose/insulin tolerance and hepatic insulin sensitivity in APPswe/PSEN1dE9 mice.
654	23223021	Our results demonstrate that Aβ induces hepatic insulin resistance in vivo via JAK2, suggesting that inhibition of Aβ signaling is a new strategy toward resolving insulin resistance and T2DM.
655	24002896	Furthermore, histological analysis indicated that the infected grafts with overexpression of SOCS1 showed strong insulin secretion function and decreased apoptosis in the early post-transplant period.