Ignet

Gene Information

Gene symbol: GSK3A

Gene name: glycogen synthase kinase 3 alpha

HGNC ID: 4616

Related Genes

#	Gene Symbol	Number of hits
1	AKT1	1 hits
2	APLP2	1 hits
3	AXIN1	1 hits
4	DEAF1	1 hits
5	GCG	1 hits
6	GSK3B	1 hits
7	INS	1 hits
8	IRS1	1 hits
9	MAPKAP1	1 hits
10	MAPT	1 hits
11	PIK3CA	1 hits
12	PPP1CA	1 hits
13	PPP1R3C	1 hits
14	PTK2B	1 hits
15	TBC1D4	1 hits

Related Sentences

#	PMID	Sentence
1	8526919	Insulin decreases the glycogen synthase kinase-3 alpha mRNA levels by altering its stability in streptozotocin-induced diabetic rat liver.
2	8526919	The chronic effect of insulin on the expression of the glycogen synthase kinase-3 alpha gene in streptozotocin-induced diabetic rat liver is examined.
3	8526919	The mRNA levels of glycogen synthase kinase-3 alpha were increased (143% of normal levels) in diabetic livers and these were normalized by insulin supplementation to the diabetic animals.
4	8526919	Neither diabetes nor insulin supplementation to diabetic rats altered the transcription rate of glycogen synthase kinase-3 alpha.
5	8526919	Insulin supplementation to the incubation medium of diabetic hepatocytes decreased the half-life of glycogen synthase kinase-3 alpha mRNA to a level comparable with normal values.
6	8526919	This study suggests that the chronic effect of insulin decreases the levels of glycogen synthase kinase-3 alpha mRNA by altering its stability.
7	8526919	Insulin decreases the glycogen synthase kinase-3 alpha mRNA levels by altering its stability in streptozotocin-induced diabetic rat liver.
8	8526919	The chronic effect of insulin on the expression of the glycogen synthase kinase-3 alpha gene in streptozotocin-induced diabetic rat liver is examined.
9	8526919	The mRNA levels of glycogen synthase kinase-3 alpha were increased (143% of normal levels) in diabetic livers and these were normalized by insulin supplementation to the diabetic animals.
10	8526919	Neither diabetes nor insulin supplementation to diabetic rats altered the transcription rate of glycogen synthase kinase-3 alpha.
11	8526919	Insulin supplementation to the incubation medium of diabetic hepatocytes decreased the half-life of glycogen synthase kinase-3 alpha mRNA to a level comparable with normal values.
12	8526919	This study suggests that the chronic effect of insulin decreases the levels of glycogen synthase kinase-3 alpha mRNA by altering its stability.
13	8526919	Insulin decreases the glycogen synthase kinase-3 alpha mRNA levels by altering its stability in streptozotocin-induced diabetic rat liver.
14	8526919	The chronic effect of insulin on the expression of the glycogen synthase kinase-3 alpha gene in streptozotocin-induced diabetic rat liver is examined.
15	8526919	The mRNA levels of glycogen synthase kinase-3 alpha were increased (143% of normal levels) in diabetic livers and these were normalized by insulin supplementation to the diabetic animals.
16	8526919	Neither diabetes nor insulin supplementation to diabetic rats altered the transcription rate of glycogen synthase kinase-3 alpha.
17	8526919	Insulin supplementation to the incubation medium of diabetic hepatocytes decreased the half-life of glycogen synthase kinase-3 alpha mRNA to a level comparable with normal values.
18	8526919	This study suggests that the chronic effect of insulin decreases the levels of glycogen synthase kinase-3 alpha mRNA by altering its stability.
19	8526919	Insulin decreases the glycogen synthase kinase-3 alpha mRNA levels by altering its stability in streptozotocin-induced diabetic rat liver.
20	8526919	The chronic effect of insulin on the expression of the glycogen synthase kinase-3 alpha gene in streptozotocin-induced diabetic rat liver is examined.
21	8526919	The mRNA levels of glycogen synthase kinase-3 alpha were increased (143% of normal levels) in diabetic livers and these were normalized by insulin supplementation to the diabetic animals.
22	8526919	Neither diabetes nor insulin supplementation to diabetic rats altered the transcription rate of glycogen synthase kinase-3 alpha.
23	8526919	Insulin supplementation to the incubation medium of diabetic hepatocytes decreased the half-life of glycogen synthase kinase-3 alpha mRNA to a level comparable with normal values.
24	8526919	This study suggests that the chronic effect of insulin decreases the levels of glycogen synthase kinase-3 alpha mRNA by altering its stability.
25	8526919	Insulin decreases the glycogen synthase kinase-3 alpha mRNA levels by altering its stability in streptozotocin-induced diabetic rat liver.
26	8526919	The chronic effect of insulin on the expression of the glycogen synthase kinase-3 alpha gene in streptozotocin-induced diabetic rat liver is examined.
27	8526919	The mRNA levels of glycogen synthase kinase-3 alpha were increased (143% of normal levels) in diabetic livers and these were normalized by insulin supplementation to the diabetic animals.
28	8526919	Neither diabetes nor insulin supplementation to diabetic rats altered the transcription rate of glycogen synthase kinase-3 alpha.
29	8526919	Insulin supplementation to the incubation medium of diabetic hepatocytes decreased the half-life of glycogen synthase kinase-3 alpha mRNA to a level comparable with normal values.
30	8526919	This study suggests that the chronic effect of insulin decreases the levels of glycogen synthase kinase-3 alpha mRNA by altering its stability.
31	8526919	Insulin decreases the glycogen synthase kinase-3 alpha mRNA levels by altering its stability in streptozotocin-induced diabetic rat liver.
32	8526919	The chronic effect of insulin on the expression of the glycogen synthase kinase-3 alpha gene in streptozotocin-induced diabetic rat liver is examined.
33	8526919	The mRNA levels of glycogen synthase kinase-3 alpha were increased (143% of normal levels) in diabetic livers and these were normalized by insulin supplementation to the diabetic animals.
34	8526919	Neither diabetes nor insulin supplementation to diabetic rats altered the transcription rate of glycogen synthase kinase-3 alpha.
35	8526919	Insulin supplementation to the incubation medium of diabetic hepatocytes decreased the half-life of glycogen synthase kinase-3 alpha mRNA to a level comparable with normal values.
36	8526919	This study suggests that the chronic effect of insulin decreases the levels of glycogen synthase kinase-3 alpha mRNA by altering its stability.
37	9267989	Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active dephosphorylated state.
38	9267989	In a search for genetic defects responsible for the decreased insulin stimulated glycogen synthesis seen in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their glucose-tolerant first-degree relatives we have performed mutational analysis of the coding region of the 2 isoforms of GSK-3alpha and GSK-3beta in 72 NIDDM patients and 12 control subjects.
39	9267989	Mapping of the GSK-3alpha to chromosome 19q13.1-13.2 and the GSK-3beta to chromosome 3q13.3-q21 outside known genetic loci linked to NIDDM further makes it unlikely that these genes are involved in the pathogenesis of common forms of NIDDM.
40	9267989	Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active dephosphorylated state.
41	9267989	In a search for genetic defects responsible for the decreased insulin stimulated glycogen synthesis seen in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their glucose-tolerant first-degree relatives we have performed mutational analysis of the coding region of the 2 isoforms of GSK-3alpha and GSK-3beta in 72 NIDDM patients and 12 control subjects.
42	9267989	Mapping of the GSK-3alpha to chromosome 19q13.1-13.2 and the GSK-3beta to chromosome 3q13.3-q21 outside known genetic loci linked to NIDDM further makes it unlikely that these genes are involved in the pathogenesis of common forms of NIDDM.
43	10455163	Part of the mechanism by which insulin stimulates glycogen synthesis may involve phosphorylation and activation of Akt, serine phosphorylation and deactivation of glycogen synthase kinase-3 (GSK-3), leading to dephosphorylation and activation of glycogen synthase.
44	10455163	To study Akt and GSK-3 regulation in muscle, time course experiments on the effects of insulin injection and treadmill running exercise were performed in hindlimb skeletal muscle from male rats.
45	10455163	Insulin stimulation significantly increased Akt phosphorylation and activity, whereas exercise had no effect.
46	10455163	The time course of the insulin-stimulated increase in Akt was closely matched by GSK-3alpha Ser(21) phosphorylation and a 40-60% decrease in GSK-3alpha and GSK-3beta activity.
47	10455163	These data suggest the following: 1) GSK-3 is constitutively active and tyrosine phosphorylated under basal conditions in skeletal muscle, 2) both exercise and insulin are effective regulators of GSK-3 activity in vivo, 3) the insulin-induced deactivation of GSK-3 occurs in response to increased Akt activity and GSK-3 serine phosphorylation, and 4) there is an Akt-independent mechanism for deactivation of GSK-3 in skeletal muscle.
48	10868943	The specific activity of GSK-3alpha did not differ between nondiabetic and diabetic muscle and was decreased similarly after 3-h insulin infusion.
49	11272135	We observed a small but significant increase in GSK3alpha (10-20%) activity in biopsies obtained from vastus lateralis after both low- and high-intensity exercise, whereas GSK3beta activity was unaffected.
50	11272135	Subsequent food intake increased Aktphosphorylation (approximately 2-fold) and deactivated GSK3alpha (approximately 40%), whereas GSK3beta activity was unchanged.
51	11272135	We conclude that GSK3alpha but not GSK3beta may have a role in the regulation of GS activity in response to meal-associated hyperinsulinemia in humans.
52	11272135	We observed a small but significant increase in GSK3alpha (10-20%) activity in biopsies obtained from vastus lateralis after both low- and high-intensity exercise, whereas GSK3beta activity was unaffected.
53	11272135	Subsequent food intake increased Aktphosphorylation (approximately 2-fold) and deactivated GSK3alpha (approximately 40%), whereas GSK3beta activity was unchanged.
54	11272135	We conclude that GSK3alpha but not GSK3beta may have a role in the regulation of GS activity in response to meal-associated hyperinsulinemia in humans.
55	11272135	We observed a small but significant increase in GSK3alpha (10-20%) activity in biopsies obtained from vastus lateralis after both low- and high-intensity exercise, whereas GSK3beta activity was unaffected.
56	11272135	Subsequent food intake increased Aktphosphorylation (approximately 2-fold) and deactivated GSK3alpha (approximately 40%), whereas GSK3beta activity was unchanged.
57	11272135	We conclude that GSK3alpha but not GSK3beta may have a role in the regulation of GS activity in response to meal-associated hyperinsulinemia in humans.
58	11872654	Insulin increased insulin receptor tyrosine kinase (IRTK), insulin receptor substrate 1-associated phosphatidylinositol (PI) 3-kinase activities, and Ser(473) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs.
59	11872654	Furthermore, insulin significantly decreased glycogen synthase kinase-3alpha (GSK-3alpha) activity equally in both legs.
60	11872654	We conclude that 1) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle; 2) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK, PI 3-kinase, PKB/Akt, or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations; and 3) exercise reduces the detrimental effects of caffeine on insulin action in muscle.
61	11872654	Insulin increased insulin receptor tyrosine kinase (IRTK), insulin receptor substrate 1-associated phosphatidylinositol (PI) 3-kinase activities, and Ser(473) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs.
62	11872654	Furthermore, insulin significantly decreased glycogen synthase kinase-3alpha (GSK-3alpha) activity equally in both legs.
63	11872654	We conclude that 1) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle; 2) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK, PI 3-kinase, PKB/Akt, or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations; and 3) exercise reduces the detrimental effects of caffeine on insulin action in muscle.
64	11978789	Glucagon-like peptide-2 receptor activation engages bad and glycogen synthase kinase-3 in a protein kinase A-dependent manner and prevents apoptosis following inhibition of phosphatidylinositol 3-kinase.
65	11978789	We now demonstrate that GLP-2, in a cycloheximide-insensitive manner, enhanced survival in baby hamster kidney cells stably transfected with the rat GLP-2R; reduced mitochondrial cytochrome c efflux; and attenuated the caspase-dependent cleavage of Akt, poly(ADP-ribose) polymerase, and beta-catenin following inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002.
66	11978789	The prosurvival effects of GLP-2 on LY294002-induced cell death were independent of Akt, p90(Rsk), or p70 S6 kinase activation; were mimicked by forskolin; and were abrogated by inhibition of protein kinase A (PKA) activity.
67	11978789	GLP-2 inhibited activation of glycogen synthase kinase-3 (GSK-3) through phosphorylation at Ser(21) in GSK-3alpha and at Ser(9) in GSK-3beta in a PI3K-independent, PKA-dependent manner.
68	11978789	GLP-2 reduced LY294002-induced mitochondrial association of endogenous Bad and Bax and stimulated phosphorylation of a transfected Bad fusion protein at Ser(155) in a PI3K-independent, but H89-sensitive manner, a modification known to suppress Bad pro-apoptotic activity.
69	11978789	These results suggest that GLP-2R signaling enhances cell survival independently of PI3K/Akt by inhibiting the activity of a subset of pro-apoptotic downstream targets of Akt in a PKA-dependent manner.
70	12095990	Fatty acid infusion selectively impairs insulin action on Akt1 and protein kinase C lambda /zeta but not on glycogen synthase kinase-3.
71	12095990	To determine the mechanism(s) for insulin resistance induced by fatty acids, we measured the ability of insulin to activate phosphoinositide 3-kinase (PI3K) and multiple distal pathways in rats.
72	12095990	Insulin stimulated IRS-1-associated PI3K activity in muscle of glycerol-infused rats 2.4-fold but had no effect in lipid-infused rats.
73	12095990	IRS-2- and phosphotyrosine-associated PI3K activity were increased 3.5- and 4.8-fold, respectively, by insulin in glycerol-infused rats but only 1.6- and 2.3-fold in lipid-infused rats.
74	12095990	Insulin increased Akt1 activity 3.9-fold in glycerol-infused rats, and this was impaired 41% in lipid-infused rats.
75	12095990	Insulin action on Akt2 and p70S6K were not impaired, whereas activation of protein kinase C lambda/zeta activity was reduced 47%.
76	12095990	Insulin inhibited glycogen synthase kinase 3alpha (GSK-3alpha) activity by 30% and GSK-3beta activity by approximately 65% and increased protein phosphatase-1 activity by 40-47% in both glycerol- and lipid-infused rats.
77	12095990	Thus, 1) elevation of fatty acids differentially affects insulin action on pathways distal to PI3K, impairing activation of Akt1 and protein kinase C lambda/zeta and 2) insulin action on glycogen synthase can be regulated independent of effects on GSK-3 and protein phosphatase-1 activity in vivo.
78	12111750	Two forms of the enzyme, GSK-3alpha and GSK-3beta, have been previously identified.
79	15178423	Whether physical exercise alters Akt and GSK3 activity in human skeletal muscle is controversial. beta-Catenin, a GSK3 substrate and important Wnt signaling protein that alters gene transcription, has not been investigated in human skeletal muscle.
80	15178423	Increases in Akt activity were accompanied by increases in Akt Thr(308) and Ser(473) phosphorylation, decreased GSK3alpha activity ( approximately 30% at both intensities), and increased phosphorylation of GSK3alpha Ser(21).
81	15178423	Exercise at both intensities also decreased beta-catenin Ser(33/37)Thr(41) phosphorylation (50-60% at both intensities).
82	15178423	These results demonstrate that Akt, GSK3, and beta-catenin signaling are regulated by exercise in human skeletal muscle, and as such identify them as possible molecular mediators of exercise's effect on metabolic and transcriptional processes in skeletal muscle.
83	15194499	In myotubes established from type 2 diabetic and healthy control subjects we determined GS activity ratio, protein expression, and activity of GSK-3alpha and beta under basal and insulin-stimulated conditions when precultured in increasing insulin concentrations.
84	15194499	In myotubes precultured at low insulin concentrations acute insulin stimulation increased GS activity more in control than in diabetic subjects, whereas the corresponding GSK-3alpha but not GSK-3beta activity was significantly reduced by acute insulin treatment in both groups.
85	15194499	However, in myotubes precultured at high insulin concentrations the effect of insulin on GS and GSK-3alpha activity was blunted in both groups.
86	15194499	In conclusion, myotubes with a primary defect in GS activity express insulin responsive GSK-3alpha, suggesting that failure of insulin to decrease GS phosphorylation involves abnormal activity of another kinase or phosphatase.
87	15194499	In myotubes established from type 2 diabetic and healthy control subjects we determined GS activity ratio, protein expression, and activity of GSK-3alpha and beta under basal and insulin-stimulated conditions when precultured in increasing insulin concentrations.
88	15194499	In myotubes precultured at low insulin concentrations acute insulin stimulation increased GS activity more in control than in diabetic subjects, whereas the corresponding GSK-3alpha but not GSK-3beta activity was significantly reduced by acute insulin treatment in both groups.
89	15194499	However, in myotubes precultured at high insulin concentrations the effect of insulin on GS and GSK-3alpha activity was blunted in both groups.
90	15194499	In conclusion, myotubes with a primary defect in GS activity express insulin responsive GSK-3alpha, suggesting that failure of insulin to decrease GS phosphorylation involves abnormal activity of another kinase or phosphatase.
91	15194499	In myotubes established from type 2 diabetic and healthy control subjects we determined GS activity ratio, protein expression, and activity of GSK-3alpha and beta under basal and insulin-stimulated conditions when precultured in increasing insulin concentrations.
92	15194499	In myotubes precultured at low insulin concentrations acute insulin stimulation increased GS activity more in control than in diabetic subjects, whereas the corresponding GSK-3alpha but not GSK-3beta activity was significantly reduced by acute insulin treatment in both groups.
93	15194499	However, in myotubes precultured at high insulin concentrations the effect of insulin on GS and GSK-3alpha activity was blunted in both groups.
94	15194499	In conclusion, myotubes with a primary defect in GS activity express insulin responsive GSK-3alpha, suggesting that failure of insulin to decrease GS phosphorylation involves abnormal activity of another kinase or phosphatase.
95	15194499	In myotubes established from type 2 diabetic and healthy control subjects we determined GS activity ratio, protein expression, and activity of GSK-3alpha and beta under basal and insulin-stimulated conditions when precultured in increasing insulin concentrations.
96	15194499	In myotubes precultured at low insulin concentrations acute insulin stimulation increased GS activity more in control than in diabetic subjects, whereas the corresponding GSK-3alpha but not GSK-3beta activity was significantly reduced by acute insulin treatment in both groups.
97	15194499	However, in myotubes precultured at high insulin concentrations the effect of insulin on GS and GSK-3alpha activity was blunted in both groups.
98	15194499	In conclusion, myotubes with a primary defect in GS activity express insulin responsive GSK-3alpha, suggesting that failure of insulin to decrease GS phosphorylation involves abnormal activity of another kinase or phosphatase.
99	15559249	Three closely related forms of glycogen synthase kinase 3 (GSK-3alpha, GSK-3beta and GSK-3beta2) have a major role in Wnt and Hedgehog signaling pathways and regulate the cell-division cycle, stem-cell renewal and differentiation, apoptosis, circadian rhythm, transcription and insulin action.
100	15559249	GSK-3, as part of a multi-protein complex that contains proteins such as axin, presenilin and beta-catenin, contains many additional target sites for specific modulation of its activity.
101	15671078	Type I soleus and type IIb epitrochlearis muscles from female obese Zucker rats were incubated in the absence or presence of a selective, small organic GSK3 inhibitor (1 microM CT118637, Ki < 10 nM for GSK3alpha and GSK3beta).
102	15671078	Maximal insulin stimulation (5 mU/ml) of glucose transport activity, glycogen synthase activity, and selected insulin-signaling factors [tyrosine phosphorylation of insulin receptor (IR) and IRS-1, IRS-1 associated with p85 subunit of phosphatidylinositol 3-kinase, and serine phosphorylation of Akt and GSK3] were assessed.
103	15671078	However, in obese soleus, GSK3 inhibition enhanced (all P < 0.05) insulin-stimulated IRS-1 tyrosine phosphorylation (45%), IRS-1-associated p85 (72%), Akt1/2 serine phosphorylation (30%), and GSK3beta serine phosphorylation (39%).
104	16176184	Insulin inhibits GSK3 by promoting phosphorylation of a serine residue (Ser-21 in GSK3alpha, Ser-9 in GSK3beta), thereby relieving GSK3 inhibition of glycogen synthesis in muscle.
105	16176184	GSK3 inhibition in liver reduces expression of the gluconeogenic genes PEPCK (phosphoenolpyruvate carboxykinase), G6Pase (glucose-6-phosphatase), as well as IGFBP1 (insulin-like growth factor binding protein-1).
106	16176184	Interestingly, insulin injection of wild-type mice, which activates PKB (protein kinase B) and inhibits GSK3 to a greater degree than feeding (50% versus 25%), does not repress these genes.
107	16412093	Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway.
108	16412093	The insulin-resistant brain state is related to late-onset sporadic Alzheimer's disease, and alterations in the insulin receptor (IR) and its downstream phosphatidylinositol-3 kinase signalling pathway have been found in human brain.
109	16412093	In this study, western blot analysis performed 1 month after i.c.v. injection of STZ showed an increase of 63% in the level of phosphorylated glycogen synthase kinase-3alpha/beta (pGSK-3alpha/beta) protein in the rat hippocampus, whereas the levels of the unphosphorylated form (GSK-3alpha/beta) and protein kinase B (Akt/PKB) remained unchanged.
110	16757548	GSK-3alpha and GSK-3beta expression decreased in adipocytes (P < 0.05), whereas GSK-3alpha protein expression increased in skeletal muscle (P < 0.05).
111	16803855	In addition, lack of Akt2 did not result in alterations in basal Akt Thr(308) or basal and contraction-stimulated glycogen synthase kinase-3beta (GSK-3beta) Ser(9) phosphorylation, glycogen synthase phosphorylation, or glycogen synthase activity.
112	16803855	In contrast, in situ contraction failed to elicit normal increases in Akt T-loop Thr(308) phosphorylation and GSK-3alpha Ser(21) phosphorylation in tibialis anterior muscles from Akt2-deficient animals.
113	16803855	Our data establish a key role for Akt2 in the regulation of GSK-3alpha Ser(21) phosphorylation with contraction and add genetic evidence to support the separation of the intracellular pathways regulated by insulin and exercise that converge on glucose uptake and glycogen synthesis in skeletal muscle.
114	16803855	In addition, lack of Akt2 did not result in alterations in basal Akt Thr(308) or basal and contraction-stimulated glycogen synthase kinase-3beta (GSK-3beta) Ser(9) phosphorylation, glycogen synthase phosphorylation, or glycogen synthase activity.
115	16803855	In contrast, in situ contraction failed to elicit normal increases in Akt T-loop Thr(308) phosphorylation and GSK-3alpha Ser(21) phosphorylation in tibialis anterior muscles from Akt2-deficient animals.
116	16803855	Our data establish a key role for Akt2 in the regulation of GSK-3alpha Ser(21) phosphorylation with contraction and add genetic evidence to support the separation of the intracellular pathways regulated by insulin and exercise that converge on glucose uptake and glycogen synthesis in skeletal muscle.
117	16823721	We have recently shown that 12(S)-hydroxyeicosatetraenoic acid plays a role in the organization of actin microfilaments in rat cardiomyocytes, and that inhibition of 12-lipoxygenase abrogates insulin-stimulated GLUT4 translocation in these cells.
118	16823721	Insulin-regulated serine phosphorylation of Akt and GSK3alpha and GSK3beta was unaltered in heart and skeletal muscle of knockout mice, suggesting unaltered insulin signaling.
119	16823721	Fractionation of hind limb muscles showed that insulin had induced a prominent translocation of GLUT4 to skeletal muscle plasma membranes in control mice.
120	16823721	However, perturbation of GLUT4 translocation in skeletal muscle of knockout mice may indicate latent insulin resistance, and supports our hypothesis that eicosanoids are involved in insulin-mediated regulation of muscle glucose transport.
121	16839840	Insulin-stimulated insulin receptor substrate-2-associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise.
122	16839840	In mouse skeletal muscle, prior exercise enhances insulin-stimulated insulin receptor substrate-2 (IRS-2) signaling (Diabetes 2002;51:479-83), but it is unknown if this also occurs in humans.
123	16839840	Insulin increased (P < .05) Akt Ser473 and GSK-3alpha/beta Ser21/Ser9 phosphorylation in both trials, with the response tending to be higher in the exercise trial.
124	16839840	In conclusion, in the immediate period after an acute bout of exercise, insulin-stimulated IRS-2 signaling is enhanced in human skeletal muscle.
125	16945017	A cellular assay for measuring the inhibition of glycogen synthase kinase-3 via the accumulation of beta-catenin in Chinese hamster ovary clone K1 cells.
126	16945017	Glycogen synthase kinase-3 (GSK3) is a serine-threonine protein kinase that exists as two isozymes, GSK3alpha and GSK3beta.
127	16945017	We describe the development of a cell-based assay designed to measure the activity of GSK3 by directly measuring the accumulation of beta-catenin in Chinese hamster ovary clone K1 (CHOK1) cells.
128	16945017	Beta-catenin levels were assessed using an antibody-based staining protocol with a luminometric readout.
129	17010615	Glycogen synthase kinase-3alpha (GSK-3alpha) was recently found to be an attractive target for the treatment of Alzheimer's disease due to its dual action in the formation of both amyloid plaques and neurofibrillary tangles.
130	17100578	In mammals, GSK-3 is encoded by two genes, termed GSK-3alpha and GSK-3beta, that yield related but distinct protein-serine kinases.
131	17363741	Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity.
132	17363741	Elevated plasma levels of IL-6 are observed in insulin-resistant states.
133	17363741	Thus, IL-6 has also been suggested to promote insulin-mediated glucose utilization.
134	17363741	A 30-min pre-exposure to IL-6 did not affect insulin-stimulated glucose transport.
135	17363741	IL-6 increased phosphorylation of STAT3 (signal transducer and activator of transcription 3; P < 0.05), AMP-activated protein kinase (P = 0.063), and p38 mitogen-activated protein kinase (P < 0.05) and reduced phosphorylation of S6 ribosomal protein (P < 0.05).
136	17363741	In contrast, phosphorylation of protein kinase B/Akt, AS160 (Akt substrate of 160 kDa), and GSK3alpha/beta (glycogen synthase kinase 3alpha/beta) as well as insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity remained unaltered.
137	17363741	Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure.
138	17570255	Therefore, we assessed the functionality of proximal and distal insulin signaling elements in isolated type I (slow-twitch oxidative) soleus muscles of ZDF rats after in vitro exposure to a selective GSK-3 inhibitor (1 micromol/L CT98014, K(i) <10 nmol/L for GSK-3alpha and GSK-3beta).
139	17570255	Maximally insulin-stimulated (5 mU/mL) GSK-3beta serine phosphorylation was significantly less (35%, P < .05) in soleus muscle of ZDF rats compared with insulin-sensitive lean Zucker rats, indicating GSK-3 overactivity.
140	17570255	GSK-3 inhibition led to significant enhancement (28%) of insulin-stimulated glucose transport activity that was associated with significant up-regulation of tyrosine phosphorylation of IR (52%) and IRS-1 (50%), and with enhanced Akt Ser473 phosphorylation (48%) and GSK-3beta Ser9 phosphorylation (36%).
141	17570255	Moreover, the selective GSK-3 inhibitor induced a significant reduction in the phosphorylation of IRS-1 Ser307 (26%) and c-jun N-terminal kinases 1 and 2 (31%), a mediator of IRS-1 Ser307 phosphorylation.
142	17570255	These results indicate that selective inhibition of GSK-3 activity in type I skeletal muscle from overtly diabetic ZDF rats enhances IRS-1-dependent insulin signaling, possibly by a decrease in c-jun N-terminal kinase activation and a diminution of the deleterious effects of IRS-1 Ser307 phosphorylation.
143	18805403	Although glucose uptake in neuronal tissues is primarily non-insulin dependent, proteins involved in insulin signaling, such as insulin receptor substrate 2 (IRS2) and glucose transporter 4 (GLUT4), are present in the basal ganglia.
144	18805403	Increased IRS2 serine phosphorylation, a marker of insulin resistance, was observed in the DA-depleted striatum.
145	18805403	Decreased phosphorylation of AKT and expression of the kinase glycogen synthase kinase-3 alpha (GSK3-alpha) was also measured in the striatum of severely DA-depleted animals.
146	18830417	The hypertrophic myopathy was caused by cardiomyocyte hyperproliferation without hypertrophy and was associated with increased expression and nuclear localization of three regulators of proliferation - GATA4, cyclin D1, and c-Myc.
147	18830417	These studies, which we believe are the first in mammals to examine the role of GSK-3alpha and GSK-3beta in the heart using loss-of-function approaches, implicate GSK-3beta as a central regulator of embryonic cardiomyocyte proliferation and differentiation, as well as of outflow tract development.
148	18839067	Comparison of the active site residues of GSK-3alpha and GSK-3beta isoforms shows that all the key amino acids involved in polar interactions with the maleimides for the beta isoform are the same in the alpha isoform, except that Asp133 in the beta isoform is replaced by Glu196 in the alpha isoform.
149	19099246	There are two homologous forms of glycogen synthase kinase (GSK)-3, GSK-3alpha and GSK-3beta, which play overlapping roles in the regulation of Wnt, Hedgehog, and insulin pathways, as well as the activation of nuclear factor (NF)-kappaB-mediated gene transcription.
150	20080974	Glycogen synthase kinase-3 (GSK-3) isoforms, GSK-3alpha and GSK-3beta, are serine/threonine kinases involved in numerous cellular processes and diverse diseases, including Alzheimer disease, cancer, and diabetes.
151	20080974	Here, we describe a structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells.
152	20080974	We examined the effect of these mutations on GSK-3 activity toward Tau, activity in Wnt signaling, interaction with Axin, and GSK-3alpha/beta Tyr(279/216) phosphorylation.
153	20080974	Glycogen synthase kinase-3 (GSK-3) isoforms, GSK-3alpha and GSK-3beta, are serine/threonine kinases involved in numerous cellular processes and diverse diseases, including Alzheimer disease, cancer, and diabetes.
154	20080974	Here, we describe a structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells.
155	20080974	We examined the effect of these mutations on GSK-3 activity toward Tau, activity in Wnt signaling, interaction with Axin, and GSK-3alpha/beta Tyr(279/216) phosphorylation.
156	20080974	Glycogen synthase kinase-3 (GSK-3) isoforms, GSK-3alpha and GSK-3beta, are serine/threonine kinases involved in numerous cellular processes and diverse diseases, including Alzheimer disease, cancer, and diabetes.
157	20080974	Here, we describe a structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells.
158	20080974	We examined the effect of these mutations on GSK-3 activity toward Tau, activity in Wnt signaling, interaction with Axin, and GSK-3alpha/beta Tyr(279/216) phosphorylation.
159	20110613	In contrast, sporadic AD has been proposed to start with an insulin-resistant brain state (IRBS).We investigated the effect of IRBS induced by intracerebroventricularly (icv) administered streptozotocin (STZ) on behavior, glycogen synthase kinase-3 (GSK) alpha/beta content, and the formation of AD-like morphological hallmarks Abeta and tau protein in AbetaPP Tg2576 mice.
160	20110613	Soluble and aggregated Abeta40/42 fragments, total and phosphorylated tau protein, and GSK-3alpha/beta were determined by ELISA.
161	20110613	In Tg mice, STZ treatment increased mortality, reduced spatial cognition, and increased cerebral aggregated Abeta fragments, total tau protein, and congophilic amyloid deposits.
162	20368287	Interactome mapping of the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway identifies deformed epidermal autoregulatory factor-1 as a new glycogen synthase kinase-3 interactor.
163	20368287	In particular, we identified the deformed epidermal autoregulatory factor-1 (DEAF1) transcription factor as an interactor and in vitro substrate of GSK3A and GSK3B.
164	20368287	Moreover, GSK3 inhibitors increased DEAF1 transcriptional activity on the 5-HT1A serotonin receptor promoter.
165	20383279	Angiotensin II inhibits insulin-stimulated GLUT4 translocation and Akt activation through tyrosine nitration-dependent mechanisms.
166	20383279	Angiotensin II (Ang II) plays a major role in the pathogenesis of insulin resistance and diabetes by inhibiting insulin's metabolic and potentiating its trophic effects.
167	20383279	We found Ang II to block insulin-dependent GLUT4 translocation in L6 myotubes in an NO- and O(2)(*-)-dependent fashion suggesting the involvement of peroxynitrite.
168	20383279	This hypothesis was confirmed by the ability of Ang II to induce tyrosine nitration of the MAP kinases ERK1/2 and of protein kinase B/Akt (Akt).
169	20383279	Tyrosine nitration of ERK1/2 was required for their phosphorylation on Thr and Tyr and their subsequent activation, whereas it completely inhibited Akt phosphorylation on Ser(473) and Thr(308) as well as its activity.
170	20383279	The inhibitory effect of nitration on Akt activity was confirmed by the ability of SIN-1 to completely block GSK3alpha phosphorylation in vitro.
171	20383279	Inhibition of nitric oxide synthase and NAD(P)Hoxidase and scavenging of free radicals with myricetin restored insulin-stimulated Akt phosphorylation and GLUT4 translocation in the presence of Ang II.
172	20383279	Similar restoration was obtained by inhibiting the ERK activating kinase MEK, indicating that these kinases regulate Akt activation.
173	20383279	Taken together, our data show that Ang II inhibits insulin-mediated GLUT4 translocation in this skeletal muscle model through at least two pathways: first through the transient activation of ERK1/2 which inhibit IRS-1/2 and second through a direct inhibitory nitration of Akt.
174	20383279	They underline the role of protein nitration as a major mechanism in the regulation of Ang II and insulin signaling pathways and more particularly as a key regulator of protein kinase activity.