Ignet

Gene Information

Gene symbol: TBC1D4

Gene name: TBC1 domain family, member 4

HGNC ID: 19165

Synonyms: KIAA0603, AS160, DKFZp779C0666

Related Genes

#	Gene Symbol	Number of hits
1	ACACA	1 hits
2	AHSG	1 hits
3	AKT1	1 hits
4	AKT1S1	1 hits
5	AKT2	1 hits
6	ATIC	1 hits
7	CAMK2G	1 hits
8	CDC16	1 hits
9	FLNA	1 hits
10	GSK3A	1 hits
11	HRB	1 hits
12	INS	1 hits
13	INSR	1 hits
14	IRS1	1 hits
15	LNPEP	1 hits
16	MAPK1	1 hits
17	MAPK3	1 hits
18	NAMPT	1 hits
19	PDGFA	1 hits
20	PIK3CA	1 hits
21	PRKAA1	1 hits
22	PRKAA2	1 hits
23	PRKCA	1 hits
24	PRKCZ	1 hits
25	RAB10	1 hits
26	RAB14	1 hits
27	RAB33B	1 hits
28	RAB6A	1 hits
29	RAB8A	1 hits
30	RACGAP1	1 hits
31	RASA1	1 hits
32	RPS6KB1	1 hits
33	RUVBL2	1 hits
34	SIRT1	1 hits
35	SLC2A4	1 hits
36	STK11	1 hits
37	TBC1D1	1 hits
38	TSC2	1 hits
39	USP6	1 hits

Related Sentences

#	PMID	Sentence
1	15616009	Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity.
2	15616009	In 3T3-L1 adipocytes, insulin-stimulated GLUT4 translocation requires phosphorylation of the protein designated Akt substrate of 160 kDa (AS160).
3	15616009	Both insulin and contractions activate Akt in skeletal muscle.
4	15616009	Therefore, we assessed the effects in skeletal muscle of each stimulus on phosphorylation of proteins, including AS160, on the Akt phosphomotif.
5	15616009	Isolated rat epitrochlearis muscles were incubated with insulin (for time course and dose response), stimulated to contract, or incubated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) and used to assess the following: serine-phosphorylation of Akt (P-Akt), immunoreactivity with an antibody recognizing the Akt phosphomotif (alpha-phospho-[Ser/Thr] Akt substrate [PAS]), and PAS immunoreactivity of samples immunoprecipitated with anti-AS160.
6	15616009	Wortmannin inhibited insulin (120 nmol/l) and contraction effects on AS160 phosphorylation.
7	15616009	Incubation with AICAR caused increased phosphorylation of AMP-activated protein kinase and AS160 but not Akt.
8	15616009	Our working hypothesis is that phosphorylation of these putative Akt substrates is important for some of the insulin and contraction bioeffects.
9	15616009	Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity.
10	15616009	In 3T3-L1 adipocytes, insulin-stimulated GLUT4 translocation requires phosphorylation of the protein designated Akt substrate of 160 kDa (AS160).
11	15616009	Both insulin and contractions activate Akt in skeletal muscle.
12	15616009	Therefore, we assessed the effects in skeletal muscle of each stimulus on phosphorylation of proteins, including AS160, on the Akt phosphomotif.
13	15616009	Isolated rat epitrochlearis muscles were incubated with insulin (for time course and dose response), stimulated to contract, or incubated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) and used to assess the following: serine-phosphorylation of Akt (P-Akt), immunoreactivity with an antibody recognizing the Akt phosphomotif (alpha-phospho-[Ser/Thr] Akt substrate [PAS]), and PAS immunoreactivity of samples immunoprecipitated with anti-AS160.
14	15616009	Wortmannin inhibited insulin (120 nmol/l) and contraction effects on AS160 phosphorylation.
15	15616009	Incubation with AICAR caused increased phosphorylation of AMP-activated protein kinase and AS160 but not Akt.
16	15616009	Our working hypothesis is that phosphorylation of these putative Akt substrates is important for some of the insulin and contraction bioeffects.
17	15616009	Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity.
18	15616009	In 3T3-L1 adipocytes, insulin-stimulated GLUT4 translocation requires phosphorylation of the protein designated Akt substrate of 160 kDa (AS160).
19	15616009	Both insulin and contractions activate Akt in skeletal muscle.
20	15616009	Therefore, we assessed the effects in skeletal muscle of each stimulus on phosphorylation of proteins, including AS160, on the Akt phosphomotif.
21	15616009	Isolated rat epitrochlearis muscles were incubated with insulin (for time course and dose response), stimulated to contract, or incubated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) and used to assess the following: serine-phosphorylation of Akt (P-Akt), immunoreactivity with an antibody recognizing the Akt phosphomotif (alpha-phospho-[Ser/Thr] Akt substrate [PAS]), and PAS immunoreactivity of samples immunoprecipitated with anti-AS160.
22	15616009	Wortmannin inhibited insulin (120 nmol/l) and contraction effects on AS160 phosphorylation.
23	15616009	Incubation with AICAR caused increased phosphorylation of AMP-activated protein kinase and AS160 but not Akt.
24	15616009	Our working hypothesis is that phosphorylation of these putative Akt substrates is important for some of the insulin and contraction bioeffects.
25	15616009	Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity.
26	15616009	In 3T3-L1 adipocytes, insulin-stimulated GLUT4 translocation requires phosphorylation of the protein designated Akt substrate of 160 kDa (AS160).
27	15616009	Both insulin and contractions activate Akt in skeletal muscle.
28	15616009	Therefore, we assessed the effects in skeletal muscle of each stimulus on phosphorylation of proteins, including AS160, on the Akt phosphomotif.
29	15616009	Isolated rat epitrochlearis muscles were incubated with insulin (for time course and dose response), stimulated to contract, or incubated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) and used to assess the following: serine-phosphorylation of Akt (P-Akt), immunoreactivity with an antibody recognizing the Akt phosphomotif (alpha-phospho-[Ser/Thr] Akt substrate [PAS]), and PAS immunoreactivity of samples immunoprecipitated with anti-AS160.
30	15616009	Wortmannin inhibited insulin (120 nmol/l) and contraction effects on AS160 phosphorylation.
31	15616009	Incubation with AICAR caused increased phosphorylation of AMP-activated protein kinase and AS160 but not Akt.
32	15616009	Our working hypothesis is that phosphorylation of these putative Akt substrates is important for some of the insulin and contraction bioeffects.
33	15616009	Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity.
34	15616009	In 3T3-L1 adipocytes, insulin-stimulated GLUT4 translocation requires phosphorylation of the protein designated Akt substrate of 160 kDa (AS160).
35	15616009	Both insulin and contractions activate Akt in skeletal muscle.
36	15616009	Therefore, we assessed the effects in skeletal muscle of each stimulus on phosphorylation of proteins, including AS160, on the Akt phosphomotif.
37	15616009	Isolated rat epitrochlearis muscles were incubated with insulin (for time course and dose response), stimulated to contract, or incubated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) and used to assess the following: serine-phosphorylation of Akt (P-Akt), immunoreactivity with an antibody recognizing the Akt phosphomotif (alpha-phospho-[Ser/Thr] Akt substrate [PAS]), and PAS immunoreactivity of samples immunoprecipitated with anti-AS160.
38	15616009	Wortmannin inhibited insulin (120 nmol/l) and contraction effects on AS160 phosphorylation.
39	15616009	Incubation with AICAR caused increased phosphorylation of AMP-activated protein kinase and AS160 but not Akt.
40	15616009	Our working hypothesis is that phosphorylation of these putative Akt substrates is important for some of the insulin and contraction bioeffects.
41	15855334	Insulin increased insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation, IRS-1-associated phosphatidylinositol (PI) 3-kinase activity, and phosphorylation of Akt Ser473 and AS160, a newly described Akt substrate that plays a role in GLUT4 exocytosis, approximately 2.3 fold before treatment.
42	15855334	In conclusion, the insulin-sensitizing effects of rosiglitazone are independent of enhanced signaling of IRS-1/PI 3-kinase/Akt/AS160 in patients with newly diagnosed type 2 diabetes.
43	15919790	Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects.
44	15919790	AS160 is a newly described substrate for the protein kinase Akt that links insulin signaling and GLUT4 trafficking.
45	15919790	In this study, we determined the expression of and in vivo insulin action on AS160 in human skeletal muscle.
46	15919790	We focused on AS160, as this Akt substrate has been linked to glucose transport.
47	15919790	Insulin-stimulated AS160 phosphorylation was reduced 39% (P < 0.05) in type 2 diabetic patients.
48	15919790	Impaired AS160 phosphorylation was related to aberrant Akt signaling; insulin action on Akt Ser(473) phosphorylation was not significantly reduced in type 2 diabetic compared with control subjects, whereas Thr(308) phosphorylation was impaired 51% (P < 0.05).
49	15919790	Moreover, defects in insulin action on AS160 may impair GLUT4 trafficking in type 2 diabetes.
50	15919790	Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects.
51	15919790	AS160 is a newly described substrate for the protein kinase Akt that links insulin signaling and GLUT4 trafficking.
52	15919790	In this study, we determined the expression of and in vivo insulin action on AS160 in human skeletal muscle.
53	15919790	We focused on AS160, as this Akt substrate has been linked to glucose transport.
54	15919790	Insulin-stimulated AS160 phosphorylation was reduced 39% (P < 0.05) in type 2 diabetic patients.
55	15919790	Impaired AS160 phosphorylation was related to aberrant Akt signaling; insulin action on Akt Ser(473) phosphorylation was not significantly reduced in type 2 diabetic compared with control subjects, whereas Thr(308) phosphorylation was impaired 51% (P < 0.05).
56	15919790	Moreover, defects in insulin action on AS160 may impair GLUT4 trafficking in type 2 diabetes.
57	15919790	Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects.
58	15919790	AS160 is a newly described substrate for the protein kinase Akt that links insulin signaling and GLUT4 trafficking.
59	15919790	In this study, we determined the expression of and in vivo insulin action on AS160 in human skeletal muscle.
60	15919790	We focused on AS160, as this Akt substrate has been linked to glucose transport.
61	15919790	Insulin-stimulated AS160 phosphorylation was reduced 39% (P < 0.05) in type 2 diabetic patients.
62	15919790	Impaired AS160 phosphorylation was related to aberrant Akt signaling; insulin action on Akt Ser(473) phosphorylation was not significantly reduced in type 2 diabetic compared with control subjects, whereas Thr(308) phosphorylation was impaired 51% (P < 0.05).
63	15919790	Moreover, defects in insulin action on AS160 may impair GLUT4 trafficking in type 2 diabetes.
64	15919790	Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects.
65	15919790	AS160 is a newly described substrate for the protein kinase Akt that links insulin signaling and GLUT4 trafficking.
66	15919790	In this study, we determined the expression of and in vivo insulin action on AS160 in human skeletal muscle.
67	15919790	We focused on AS160, as this Akt substrate has been linked to glucose transport.
68	15919790	Insulin-stimulated AS160 phosphorylation was reduced 39% (P < 0.05) in type 2 diabetic patients.
69	15919790	Impaired AS160 phosphorylation was related to aberrant Akt signaling; insulin action on Akt Ser(473) phosphorylation was not significantly reduced in type 2 diabetic compared with control subjects, whereas Thr(308) phosphorylation was impaired 51% (P < 0.05).
70	15919790	Moreover, defects in insulin action on AS160 may impair GLUT4 trafficking in type 2 diabetes.
71	15919790	Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects.
72	15919790	AS160 is a newly described substrate for the protein kinase Akt that links insulin signaling and GLUT4 trafficking.
73	15919790	In this study, we determined the expression of and in vivo insulin action on AS160 in human skeletal muscle.
74	15919790	We focused on AS160, as this Akt substrate has been linked to glucose transport.
75	15919790	Insulin-stimulated AS160 phosphorylation was reduced 39% (P < 0.05) in type 2 diabetic patients.
76	15919790	Impaired AS160 phosphorylation was related to aberrant Akt signaling; insulin action on Akt Ser(473) phosphorylation was not significantly reduced in type 2 diabetic compared with control subjects, whereas Thr(308) phosphorylation was impaired 51% (P < 0.05).
77	15919790	Moreover, defects in insulin action on AS160 may impair GLUT4 trafficking in type 2 diabetes.
78	15919790	Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects.
79	15919790	AS160 is a newly described substrate for the protein kinase Akt that links insulin signaling and GLUT4 trafficking.
80	15919790	In this study, we determined the expression of and in vivo insulin action on AS160 in human skeletal muscle.
81	15919790	We focused on AS160, as this Akt substrate has been linked to glucose transport.
82	15919790	Insulin-stimulated AS160 phosphorylation was reduced 39% (P < 0.05) in type 2 diabetic patients.
83	15919790	Impaired AS160 phosphorylation was related to aberrant Akt signaling; insulin action on Akt Ser(473) phosphorylation was not significantly reduced in type 2 diabetic compared with control subjects, whereas Thr(308) phosphorylation was impaired 51% (P < 0.05).
84	15919790	Moreover, defects in insulin action on AS160 may impair GLUT4 trafficking in type 2 diabetes.
85	15919790	Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects.
86	15919790	AS160 is a newly described substrate for the protein kinase Akt that links insulin signaling and GLUT4 trafficking.
87	15919790	In this study, we determined the expression of and in vivo insulin action on AS160 in human skeletal muscle.
88	15919790	We focused on AS160, as this Akt substrate has been linked to glucose transport.
89	15919790	Insulin-stimulated AS160 phosphorylation was reduced 39% (P < 0.05) in type 2 diabetic patients.
90	15919790	Impaired AS160 phosphorylation was related to aberrant Akt signaling; insulin action on Akt Ser(473) phosphorylation was not significantly reduced in type 2 diabetic compared with control subjects, whereas Thr(308) phosphorylation was impaired 51% (P < 0.05).
91	15919790	Moreover, defects in insulin action on AS160 may impair GLUT4 trafficking in type 2 diabetes.
92	16154996	Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking.
93	16154996	Insulin stimulates the translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane.
94	16154996	In addition to previously identified components of GLUT4 storage vesicles including the insulin-regulated aminopeptidase insulin-regulated aminopeptidase and the vesicle soluble N-ethylmaleimide factor attachment protein (v-SNARE) VAMP2, we have identified three new Rab proteins, Rab10, Rab11, and Rab14, on GLUT4 vesicles.
95	16154996	We have also found that the putative Rab GTPase-activating protein AS160 (Akt substrate of 160 kDa) is associated with GLUT4 vesicles in the basal state and dissociates in response to insulin.
96	16154996	This association is likely to be mediated by the cytosolic tail of insulin-regulated aminopeptidase, which interacted both in vitro and in vivo with AS160.
97	16154996	Consistent with an inhibitory role of AS160 in the basal state, reduced expression of AS160 in adipocytes using short hairpin RNA increased plasma membrane levels of GLUT4 in an insulin-independent manner.
98	16154996	These findings support an important role for AS160 in the insulin regulated trafficking of GLUT4.
99	16154996	Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking.
100	16154996	Insulin stimulates the translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane.
101	16154996	In addition to previously identified components of GLUT4 storage vesicles including the insulin-regulated aminopeptidase insulin-regulated aminopeptidase and the vesicle soluble N-ethylmaleimide factor attachment protein (v-SNARE) VAMP2, we have identified three new Rab proteins, Rab10, Rab11, and Rab14, on GLUT4 vesicles.
102	16154996	We have also found that the putative Rab GTPase-activating protein AS160 (Akt substrate of 160 kDa) is associated with GLUT4 vesicles in the basal state and dissociates in response to insulin.
103	16154996	This association is likely to be mediated by the cytosolic tail of insulin-regulated aminopeptidase, which interacted both in vitro and in vivo with AS160.
104	16154996	Consistent with an inhibitory role of AS160 in the basal state, reduced expression of AS160 in adipocytes using short hairpin RNA increased plasma membrane levels of GLUT4 in an insulin-independent manner.
105	16154996	These findings support an important role for AS160 in the insulin regulated trafficking of GLUT4.
106	16154996	Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking.
107	16154996	Insulin stimulates the translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane.
108	16154996	In addition to previously identified components of GLUT4 storage vesicles including the insulin-regulated aminopeptidase insulin-regulated aminopeptidase and the vesicle soluble N-ethylmaleimide factor attachment protein (v-SNARE) VAMP2, we have identified three new Rab proteins, Rab10, Rab11, and Rab14, on GLUT4 vesicles.
109	16154996	We have also found that the putative Rab GTPase-activating protein AS160 (Akt substrate of 160 kDa) is associated with GLUT4 vesicles in the basal state and dissociates in response to insulin.
110	16154996	This association is likely to be mediated by the cytosolic tail of insulin-regulated aminopeptidase, which interacted both in vitro and in vivo with AS160.
111	16154996	Consistent with an inhibitory role of AS160 in the basal state, reduced expression of AS160 in adipocytes using short hairpin RNA increased plasma membrane levels of GLUT4 in an insulin-independent manner.
112	16154996	These findings support an important role for AS160 in the insulin regulated trafficking of GLUT4.
113	16154996	Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking.
114	16154996	Insulin stimulates the translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane.
115	16154996	In addition to previously identified components of GLUT4 storage vesicles including the insulin-regulated aminopeptidase insulin-regulated aminopeptidase and the vesicle soluble N-ethylmaleimide factor attachment protein (v-SNARE) VAMP2, we have identified three new Rab proteins, Rab10, Rab11, and Rab14, on GLUT4 vesicles.
116	16154996	We have also found that the putative Rab GTPase-activating protein AS160 (Akt substrate of 160 kDa) is associated with GLUT4 vesicles in the basal state and dissociates in response to insulin.
117	16154996	This association is likely to be mediated by the cytosolic tail of insulin-regulated aminopeptidase, which interacted both in vitro and in vivo with AS160.
118	16154996	Consistent with an inhibitory role of AS160 in the basal state, reduced expression of AS160 in adipocytes using short hairpin RNA increased plasma membrane levels of GLUT4 in an insulin-independent manner.
119	16154996	These findings support an important role for AS160 in the insulin regulated trafficking of GLUT4.
120	16154996	Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking.
121	16154996	Insulin stimulates the translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane.
122	16154996	In addition to previously identified components of GLUT4 storage vesicles including the insulin-regulated aminopeptidase insulin-regulated aminopeptidase and the vesicle soluble N-ethylmaleimide factor attachment protein (v-SNARE) VAMP2, we have identified three new Rab proteins, Rab10, Rab11, and Rab14, on GLUT4 vesicles.
123	16154996	We have also found that the putative Rab GTPase-activating protein AS160 (Akt substrate of 160 kDa) is associated with GLUT4 vesicles in the basal state and dissociates in response to insulin.
124	16154996	This association is likely to be mediated by the cytosolic tail of insulin-regulated aminopeptidase, which interacted both in vitro and in vivo with AS160.
125	16154996	Consistent with an inhibitory role of AS160 in the basal state, reduced expression of AS160 in adipocytes using short hairpin RNA increased plasma membrane levels of GLUT4 in an insulin-independent manner.
126	16154996	These findings support an important role for AS160 in the insulin regulated trafficking of GLUT4.
127	16319959	Insulin promotes glucose uptake into muscle and adipose tissues through glucose transporter 4 (GLUT4).
128	16319959	The coordinated action of phosphatidylinositol 3-kinase effectors, protein kinase Akt, atypical protein kinase C (aPKC) and Akt substrate of 160-kDa (AS160), regulates the GLUT4 cycle by affecting its translocation, fusion with the plasma membrane, internalization and sorting.
129	16319959	We review the evidence that supports such cycling, evaluate current models proposing static or dynamic retention, and highlight how distinct steps of GLUT4 transport are regulated by insulin signals.
130	16319959	In particular, fusion seems to be regulated by aPKC (via munc18) and Akt (via syntaxin4-interacting protein (synip)).
131	16319959	AS160 participates in GLUT4 intracellular retention, and possibly fusion, through candidate ras-related GTP-binding protein (Rab)2, Rab8, Rab10 and/or Rab14.
132	16319959	The localization of the insulin-sensitive GLUT4 compartment and the precise target of insulin-derived signals remain open for future investigation.
133	16319959	Insulin promotes glucose uptake into muscle and adipose tissues through glucose transporter 4 (GLUT4).
134	16319959	The coordinated action of phosphatidylinositol 3-kinase effectors, protein kinase Akt, atypical protein kinase C (aPKC) and Akt substrate of 160-kDa (AS160), regulates the GLUT4 cycle by affecting its translocation, fusion with the plasma membrane, internalization and sorting.
135	16319959	We review the evidence that supports such cycling, evaluate current models proposing static or dynamic retention, and highlight how distinct steps of GLUT4 transport are regulated by insulin signals.
136	16319959	In particular, fusion seems to be regulated by aPKC (via munc18) and Akt (via syntaxin4-interacting protein (synip)).
137	16319959	AS160 participates in GLUT4 intracellular retention, and possibly fusion, through candidate ras-related GTP-binding protein (Rab)2, Rab8, Rab10 and/or Rab14.
138	16319959	The localization of the insulin-sensitive GLUT4 compartment and the precise target of insulin-derived signals remain open for future investigation.
139	16644684	Insulin increased phosphorylation of Akt and Akt substrate of 160 kDa (AS160) in a dose-dependent manner, with comparable responses between groups.
140	16644684	Skeletal muscle mRNA expression of peroxisome proliferator-activated receptor (PPAR) gamma coactivator (PGC)-1alpha, PGC-1beta, PPARdelta, nuclear respiratory factor-1, and uncoupling protein-3 was comparable between first-degree relatives and control subjects.
141	16644684	In conclusion, the uncoupling of insulin action on Akt/AS160 signaling and glucose transport implicates defective GLUT4 trafficking as an early event in the pathogenesis of type 2 diabetes.
142	16644684	Insulin increased phosphorylation of Akt and Akt substrate of 160 kDa (AS160) in a dose-dependent manner, with comparable responses between groups.
143	16644684	Skeletal muscle mRNA expression of peroxisome proliferator-activated receptor (PPAR) gamma coactivator (PGC)-1alpha, PGC-1beta, PPARdelta, nuclear respiratory factor-1, and uncoupling protein-3 was comparable between first-degree relatives and control subjects.
144	16644684	In conclusion, the uncoupling of insulin action on Akt/AS160 signaling and glucose transport implicates defective GLUT4 trafficking as an early event in the pathogenesis of type 2 diabetes.
145	16731842	Exercise-induced phosphorylation of the novel Akt substrates AS160 and filamin A in human skeletal muscle.
146	16804075	AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.
147	16804075	AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR).
148	16804075	AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake.
149	16804075	We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle.
150	16804075	In mice deficient in AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle.
151	16804075	AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.
152	16804075	AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR).
153	16804075	AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake.
154	16804075	We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle.
155	16804075	In mice deficient in AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle.
156	16804077	Insulin and contraction increase GLUT4 translocation in skeletal muscle via distinct signaling mechanisms.
157	16804077	Akt substrate of 160 kDa (AS160) mediates insulin-stimulated GLUT4 translocation in L6 myotubes, presumably through activation of Akt.
158	16804077	Using in vivo, in vitro, and in situ methods, insulin, contraction, and the AMP-activated protein kinase (AMPK) activator AICAR all increased AS160 phosphorylation in mouse skeletal muscle.
159	16804077	To determine if AMPK mediates AS160 signaling, we used AMPK alpha2-inactive (alpha2i) transgenic mice.
160	16804077	AICAR-stimulated AS160 phosphorylation was fully inhibited, whereas contraction-stimulated AS160 phosphorylation was partially reduced in the AMPK alpha2i transgenic mice.
161	16804077	Combined AMPK alpha2 and Akt inhibition by wortmannin treatment of AMPK alpha2 transgenic mice did not fully ablate contraction-stimulated AS160 phosphorylation.
162	16804077	While Akt and AMPK alpha2 activities are essential for AS160 phosphorylation by insulin and AICAR, respectively, neither kinase is indispensable for the entire effects of contraction on AS160 phosphorylation.
163	16804077	Insulin and contraction increase GLUT4 translocation in skeletal muscle via distinct signaling mechanisms.
164	16804077	Akt substrate of 160 kDa (AS160) mediates insulin-stimulated GLUT4 translocation in L6 myotubes, presumably through activation of Akt.
165	16804077	Using in vivo, in vitro, and in situ methods, insulin, contraction, and the AMP-activated protein kinase (AMPK) activator AICAR all increased AS160 phosphorylation in mouse skeletal muscle.
166	16804077	To determine if AMPK mediates AS160 signaling, we used AMPK alpha2-inactive (alpha2i) transgenic mice.
167	16804077	AICAR-stimulated AS160 phosphorylation was fully inhibited, whereas contraction-stimulated AS160 phosphorylation was partially reduced in the AMPK alpha2i transgenic mice.
168	16804077	Combined AMPK alpha2 and Akt inhibition by wortmannin treatment of AMPK alpha2 transgenic mice did not fully ablate contraction-stimulated AS160 phosphorylation.
169	16804077	While Akt and AMPK alpha2 activities are essential for AS160 phosphorylation by insulin and AICAR, respectively, neither kinase is indispensable for the entire effects of contraction on AS160 phosphorylation.
170	16880201	A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160.
171	16880201	Translocation of the insulin-regulated glucose transporter GLUT4 to the cell surface is dependent on the phosphatidylinositol 3-kinase/Akt pathway.
172	16880201	The RabGAP (Rab GTPase-activating protein) AS160 (Akt substrate of 160 kDa) is a direct substrate of Akt and plays an essential role in the regulation of GLUT4 trafficking.
173	16880201	We have used liquid chromatography tandem mass spectrometry to identify several 14-3-3 isoforms as AS160-interacting proteins. 14-3-3 proteins interact with AS160 in an insulin- and Akt-dependent manner via an Akt phosphorylation site, Thr-642.
174	16880201	This correlates with the dominant negative effect of both the AS160(T642A) and the AS160(4P) mutants on insulin-stimulated GLUT4 translocation.
175	16880201	Introduction of a constitutive 14-3-3 binding site into AS160(4P) restored 14-3-3 binding without disrupting AS160-IRAP (insulin-responsive amino peptidase) interaction and reversed the inhibitory effect of AS160(4P) on GLUT4 translocation.
176	16880201	These data show that the insulin-dependent association of 14-3-3 with AS160 plays an important role in GLUT4 trafficking in adipocytes.
177	16880201	A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160.
178	16880201	Translocation of the insulin-regulated glucose transporter GLUT4 to the cell surface is dependent on the phosphatidylinositol 3-kinase/Akt pathway.
179	16880201	The RabGAP (Rab GTPase-activating protein) AS160 (Akt substrate of 160 kDa) is a direct substrate of Akt and plays an essential role in the regulation of GLUT4 trafficking.
180	16880201	We have used liquid chromatography tandem mass spectrometry to identify several 14-3-3 isoforms as AS160-interacting proteins. 14-3-3 proteins interact with AS160 in an insulin- and Akt-dependent manner via an Akt phosphorylation site, Thr-642.
181	16880201	This correlates with the dominant negative effect of both the AS160(T642A) and the AS160(4P) mutants on insulin-stimulated GLUT4 translocation.
182	16880201	Introduction of a constitutive 14-3-3 binding site into AS160(4P) restored 14-3-3 binding without disrupting AS160-IRAP (insulin-responsive amino peptidase) interaction and reversed the inhibitory effect of AS160(4P) on GLUT4 translocation.
183	16880201	These data show that the insulin-dependent association of 14-3-3 with AS160 plays an important role in GLUT4 trafficking in adipocytes.
184	16880201	A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160.
185	16880201	Translocation of the insulin-regulated glucose transporter GLUT4 to the cell surface is dependent on the phosphatidylinositol 3-kinase/Akt pathway.
186	16880201	The RabGAP (Rab GTPase-activating protein) AS160 (Akt substrate of 160 kDa) is a direct substrate of Akt and plays an essential role in the regulation of GLUT4 trafficking.
187	16880201	We have used liquid chromatography tandem mass spectrometry to identify several 14-3-3 isoforms as AS160-interacting proteins. 14-3-3 proteins interact with AS160 in an insulin- and Akt-dependent manner via an Akt phosphorylation site, Thr-642.
188	16880201	This correlates with the dominant negative effect of both the AS160(T642A) and the AS160(4P) mutants on insulin-stimulated GLUT4 translocation.
189	16880201	Introduction of a constitutive 14-3-3 binding site into AS160(4P) restored 14-3-3 binding without disrupting AS160-IRAP (insulin-responsive amino peptidase) interaction and reversed the inhibitory effect of AS160(4P) on GLUT4 translocation.
190	16880201	These data show that the insulin-dependent association of 14-3-3 with AS160 plays an important role in GLUT4 trafficking in adipocytes.
191	16880201	A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160.
192	16880201	Translocation of the insulin-regulated glucose transporter GLUT4 to the cell surface is dependent on the phosphatidylinositol 3-kinase/Akt pathway.
193	16880201	The RabGAP (Rab GTPase-activating protein) AS160 (Akt substrate of 160 kDa) is a direct substrate of Akt and plays an essential role in the regulation of GLUT4 trafficking.
194	16880201	We have used liquid chromatography tandem mass spectrometry to identify several 14-3-3 isoforms as AS160-interacting proteins. 14-3-3 proteins interact with AS160 in an insulin- and Akt-dependent manner via an Akt phosphorylation site, Thr-642.
195	16880201	This correlates with the dominant negative effect of both the AS160(T642A) and the AS160(4P) mutants on insulin-stimulated GLUT4 translocation.
196	16880201	Introduction of a constitutive 14-3-3 binding site into AS160(4P) restored 14-3-3 binding without disrupting AS160-IRAP (insulin-responsive amino peptidase) interaction and reversed the inhibitory effect of AS160(4P) on GLUT4 translocation.
197	16880201	These data show that the insulin-dependent association of 14-3-3 with AS160 plays an important role in GLUT4 trafficking in adipocytes.
198	16880201	A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160.
199	16880201	Translocation of the insulin-regulated glucose transporter GLUT4 to the cell surface is dependent on the phosphatidylinositol 3-kinase/Akt pathway.
200	16880201	The RabGAP (Rab GTPase-activating protein) AS160 (Akt substrate of 160 kDa) is a direct substrate of Akt and plays an essential role in the regulation of GLUT4 trafficking.
201	16880201	We have used liquid chromatography tandem mass spectrometry to identify several 14-3-3 isoforms as AS160-interacting proteins. 14-3-3 proteins interact with AS160 in an insulin- and Akt-dependent manner via an Akt phosphorylation site, Thr-642.
202	16880201	This correlates with the dominant negative effect of both the AS160(T642A) and the AS160(4P) mutants on insulin-stimulated GLUT4 translocation.
203	16880201	Introduction of a constitutive 14-3-3 binding site into AS160(4P) restored 14-3-3 binding without disrupting AS160-IRAP (insulin-responsive amino peptidase) interaction and reversed the inhibitory effect of AS160(4P) on GLUT4 translocation.
204	16880201	These data show that the insulin-dependent association of 14-3-3 with AS160 plays an important role in GLUT4 trafficking in adipocytes.
205	16880201	A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160.
206	16880201	Translocation of the insulin-regulated glucose transporter GLUT4 to the cell surface is dependent on the phosphatidylinositol 3-kinase/Akt pathway.
207	16880201	The RabGAP (Rab GTPase-activating protein) AS160 (Akt substrate of 160 kDa) is a direct substrate of Akt and plays an essential role in the regulation of GLUT4 trafficking.
208	16880201	We have used liquid chromatography tandem mass spectrometry to identify several 14-3-3 isoforms as AS160-interacting proteins. 14-3-3 proteins interact with AS160 in an insulin- and Akt-dependent manner via an Akt phosphorylation site, Thr-642.
209	16880201	This correlates with the dominant negative effect of both the AS160(T642A) and the AS160(4P) mutants on insulin-stimulated GLUT4 translocation.
210	16880201	Introduction of a constitutive 14-3-3 binding site into AS160(4P) restored 14-3-3 binding without disrupting AS160-IRAP (insulin-responsive amino peptidase) interaction and reversed the inhibitory effect of AS160(4P) on GLUT4 translocation.
211	16880201	These data show that the insulin-dependent association of 14-3-3 with AS160 plays an important role in GLUT4 trafficking in adipocytes.
212	16935857	AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle.
213	16935857	Insulin and contraction are potent stimulators of GLUT4 translocation and increase skeletal muscle glucose uptake.
214	16935857	We recently identified the Rab GTPase-activating protein (GAP) AS160 as a putative point of convergence linking distinct upstream signaling cascades induced by insulin and contraction in mouse skeletal muscle.
215	16935857	Here, we studied the functional implications of these AS160 signaling events by using an in vivo electroporation technique to overexpress wild type and three AS160 mutants in mouse tibialis anterior muscles: 1) AS160 mutated to prevent phosphorylation on four regulatory phospho-Akt-substrate sites (4P); 2) AS160 mutated to abolish Rab GTPase activity (R/K); and 3) double mutant AS160 containing both 4P and R/K mutations (2M).
216	16935857	To determine the effects of AS160 on insulin- and contraction-stimulated glucose uptake in transfected muscles, we measured [3H]2-deoxyglucose uptake in vivo following intravenous glucose administration and in situ muscle contraction, respectively.
217	16935857	Insulin-stimulated glucose uptake was significantly inhibited in muscles overexpressing 4P mutant AS160.
218	16935857	However, this inhibition was completely prevented by concomitant disruption of AS160 Rab GAP activity.
219	16935857	In contrast, overexpressing mutant AS160 lacking Rab GAP activity resulted in increases in both sham and contraction-stimulated muscles.
220	16935857	These data suggest that AS160 regulates both insulin- and contraction-stimulated glucose metabolism in mouse skeletal muscle in vivo and that the effects of mutant AS160 on the actions of insulin and contraction are not identical.
221	16935857	AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle.
222	16935857	Insulin and contraction are potent stimulators of GLUT4 translocation and increase skeletal muscle glucose uptake.
223	16935857	We recently identified the Rab GTPase-activating protein (GAP) AS160 as a putative point of convergence linking distinct upstream signaling cascades induced by insulin and contraction in mouse skeletal muscle.
224	16935857	Here, we studied the functional implications of these AS160 signaling events by using an in vivo electroporation technique to overexpress wild type and three AS160 mutants in mouse tibialis anterior muscles: 1) AS160 mutated to prevent phosphorylation on four regulatory phospho-Akt-substrate sites (4P); 2) AS160 mutated to abolish Rab GTPase activity (R/K); and 3) double mutant AS160 containing both 4P and R/K mutations (2M).
225	16935857	To determine the effects of AS160 on insulin- and contraction-stimulated glucose uptake in transfected muscles, we measured [3H]2-deoxyglucose uptake in vivo following intravenous glucose administration and in situ muscle contraction, respectively.
226	16935857	Insulin-stimulated glucose uptake was significantly inhibited in muscles overexpressing 4P mutant AS160.
227	16935857	However, this inhibition was completely prevented by concomitant disruption of AS160 Rab GAP activity.
228	16935857	In contrast, overexpressing mutant AS160 lacking Rab GAP activity resulted in increases in both sham and contraction-stimulated muscles.
229	16935857	These data suggest that AS160 regulates both insulin- and contraction-stimulated glucose metabolism in mouse skeletal muscle in vivo and that the effects of mutant AS160 on the actions of insulin and contraction are not identical.
230	16935857	AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle.
231	16935857	Insulin and contraction are potent stimulators of GLUT4 translocation and increase skeletal muscle glucose uptake.
232	16935857	We recently identified the Rab GTPase-activating protein (GAP) AS160 as a putative point of convergence linking distinct upstream signaling cascades induced by insulin and contraction in mouse skeletal muscle.
233	16935857	Here, we studied the functional implications of these AS160 signaling events by using an in vivo electroporation technique to overexpress wild type and three AS160 mutants in mouse tibialis anterior muscles: 1) AS160 mutated to prevent phosphorylation on four regulatory phospho-Akt-substrate sites (4P); 2) AS160 mutated to abolish Rab GTPase activity (R/K); and 3) double mutant AS160 containing both 4P and R/K mutations (2M).
234	16935857	To determine the effects of AS160 on insulin- and contraction-stimulated glucose uptake in transfected muscles, we measured [3H]2-deoxyglucose uptake in vivo following intravenous glucose administration and in situ muscle contraction, respectively.
235	16935857	Insulin-stimulated glucose uptake was significantly inhibited in muscles overexpressing 4P mutant AS160.
236	16935857	However, this inhibition was completely prevented by concomitant disruption of AS160 Rab GAP activity.
237	16935857	In contrast, overexpressing mutant AS160 lacking Rab GAP activity resulted in increases in both sham and contraction-stimulated muscles.
238	16935857	These data suggest that AS160 regulates both insulin- and contraction-stimulated glucose metabolism in mouse skeletal muscle in vivo and that the effects of mutant AS160 on the actions of insulin and contraction are not identical.
239	16935857	AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle.
240	16935857	Insulin and contraction are potent stimulators of GLUT4 translocation and increase skeletal muscle glucose uptake.
241	16935857	We recently identified the Rab GTPase-activating protein (GAP) AS160 as a putative point of convergence linking distinct upstream signaling cascades induced by insulin and contraction in mouse skeletal muscle.
242	16935857	Here, we studied the functional implications of these AS160 signaling events by using an in vivo electroporation technique to overexpress wild type and three AS160 mutants in mouse tibialis anterior muscles: 1) AS160 mutated to prevent phosphorylation on four regulatory phospho-Akt-substrate sites (4P); 2) AS160 mutated to abolish Rab GTPase activity (R/K); and 3) double mutant AS160 containing both 4P and R/K mutations (2M).
243	16935857	To determine the effects of AS160 on insulin- and contraction-stimulated glucose uptake in transfected muscles, we measured [3H]2-deoxyglucose uptake in vivo following intravenous glucose administration and in situ muscle contraction, respectively.
244	16935857	Insulin-stimulated glucose uptake was significantly inhibited in muscles overexpressing 4P mutant AS160.
245	16935857	However, this inhibition was completely prevented by concomitant disruption of AS160 Rab GAP activity.
246	16935857	In contrast, overexpressing mutant AS160 lacking Rab GAP activity resulted in increases in both sham and contraction-stimulated muscles.
247	16935857	These data suggest that AS160 regulates both insulin- and contraction-stimulated glucose metabolism in mouse skeletal muscle in vivo and that the effects of mutant AS160 on the actions of insulin and contraction are not identical.
248	16935857	AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle.
249	16935857	Insulin and contraction are potent stimulators of GLUT4 translocation and increase skeletal muscle glucose uptake.
250	16935857	We recently identified the Rab GTPase-activating protein (GAP) AS160 as a putative point of convergence linking distinct upstream signaling cascades induced by insulin and contraction in mouse skeletal muscle.
251	16935857	Here, we studied the functional implications of these AS160 signaling events by using an in vivo electroporation technique to overexpress wild type and three AS160 mutants in mouse tibialis anterior muscles: 1) AS160 mutated to prevent phosphorylation on four regulatory phospho-Akt-substrate sites (4P); 2) AS160 mutated to abolish Rab GTPase activity (R/K); and 3) double mutant AS160 containing both 4P and R/K mutations (2M).
252	16935857	To determine the effects of AS160 on insulin- and contraction-stimulated glucose uptake in transfected muscles, we measured [3H]2-deoxyglucose uptake in vivo following intravenous glucose administration and in situ muscle contraction, respectively.
253	16935857	Insulin-stimulated glucose uptake was significantly inhibited in muscles overexpressing 4P mutant AS160.
254	16935857	However, this inhibition was completely prevented by concomitant disruption of AS160 Rab GAP activity.
255	16935857	In contrast, overexpressing mutant AS160 lacking Rab GAP activity resulted in increases in both sham and contraction-stimulated muscles.
256	16935857	These data suggest that AS160 regulates both insulin- and contraction-stimulated glucose metabolism in mouse skeletal muscle in vivo and that the effects of mutant AS160 on the actions of insulin and contraction are not identical.
257	16935857	AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle.
258	16935857	Insulin and contraction are potent stimulators of GLUT4 translocation and increase skeletal muscle glucose uptake.
259	16935857	We recently identified the Rab GTPase-activating protein (GAP) AS160 as a putative point of convergence linking distinct upstream signaling cascades induced by insulin and contraction in mouse skeletal muscle.
260	16935857	Here, we studied the functional implications of these AS160 signaling events by using an in vivo electroporation technique to overexpress wild type and three AS160 mutants in mouse tibialis anterior muscles: 1) AS160 mutated to prevent phosphorylation on four regulatory phospho-Akt-substrate sites (4P); 2) AS160 mutated to abolish Rab GTPase activity (R/K); and 3) double mutant AS160 containing both 4P and R/K mutations (2M).
261	16935857	To determine the effects of AS160 on insulin- and contraction-stimulated glucose uptake in transfected muscles, we measured [3H]2-deoxyglucose uptake in vivo following intravenous glucose administration and in situ muscle contraction, respectively.
262	16935857	Insulin-stimulated glucose uptake was significantly inhibited in muscles overexpressing 4P mutant AS160.
263	16935857	However, this inhibition was completely prevented by concomitant disruption of AS160 Rab GAP activity.
264	16935857	In contrast, overexpressing mutant AS160 lacking Rab GAP activity resulted in increases in both sham and contraction-stimulated muscles.
265	16935857	These data suggest that AS160 regulates both insulin- and contraction-stimulated glucose metabolism in mouse skeletal muscle in vivo and that the effects of mutant AS160 on the actions of insulin and contraction are not identical.
266	16935857	AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle.
267	16935857	Insulin and contraction are potent stimulators of GLUT4 translocation and increase skeletal muscle glucose uptake.
268	16935857	We recently identified the Rab GTPase-activating protein (GAP) AS160 as a putative point of convergence linking distinct upstream signaling cascades induced by insulin and contraction in mouse skeletal muscle.
269	16935857	Here, we studied the functional implications of these AS160 signaling events by using an in vivo electroporation technique to overexpress wild type and three AS160 mutants in mouse tibialis anterior muscles: 1) AS160 mutated to prevent phosphorylation on four regulatory phospho-Akt-substrate sites (4P); 2) AS160 mutated to abolish Rab GTPase activity (R/K); and 3) double mutant AS160 containing both 4P and R/K mutations (2M).
270	16935857	To determine the effects of AS160 on insulin- and contraction-stimulated glucose uptake in transfected muscles, we measured [3H]2-deoxyglucose uptake in vivo following intravenous glucose administration and in situ muscle contraction, respectively.
271	16935857	Insulin-stimulated glucose uptake was significantly inhibited in muscles overexpressing 4P mutant AS160.
272	16935857	However, this inhibition was completely prevented by concomitant disruption of AS160 Rab GAP activity.
273	16935857	In contrast, overexpressing mutant AS160 lacking Rab GAP activity resulted in increases in both sham and contraction-stimulated muscles.
274	16935857	These data suggest that AS160 regulates both insulin- and contraction-stimulated glucose metabolism in mouse skeletal muscle in vivo and that the effects of mutant AS160 on the actions of insulin and contraction are not identical.
275	16935857	AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle.
276	16935857	Insulin and contraction are potent stimulators of GLUT4 translocation and increase skeletal muscle glucose uptake.
277	16935857	We recently identified the Rab GTPase-activating protein (GAP) AS160 as a putative point of convergence linking distinct upstream signaling cascades induced by insulin and contraction in mouse skeletal muscle.
278	16935857	Here, we studied the functional implications of these AS160 signaling events by using an in vivo electroporation technique to overexpress wild type and three AS160 mutants in mouse tibialis anterior muscles: 1) AS160 mutated to prevent phosphorylation on four regulatory phospho-Akt-substrate sites (4P); 2) AS160 mutated to abolish Rab GTPase activity (R/K); and 3) double mutant AS160 containing both 4P and R/K mutations (2M).
279	16935857	To determine the effects of AS160 on insulin- and contraction-stimulated glucose uptake in transfected muscles, we measured [3H]2-deoxyglucose uptake in vivo following intravenous glucose administration and in situ muscle contraction, respectively.
280	16935857	Insulin-stimulated glucose uptake was significantly inhibited in muscles overexpressing 4P mutant AS160.
281	16935857	However, this inhibition was completely prevented by concomitant disruption of AS160 Rab GAP activity.
282	16935857	In contrast, overexpressing mutant AS160 lacking Rab GAP activity resulted in increases in both sham and contraction-stimulated muscles.
283	16935857	These data suggest that AS160 regulates both insulin- and contraction-stimulated glucose metabolism in mouse skeletal muscle in vivo and that the effects of mutant AS160 on the actions of insulin and contraction are not identical.
284	17259386	The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic.
285	17259386	Insulin-dependent phosphorylation of Akt target AS160 is required for GLUT4 translocation.
286	17259386	Insulin and platelet-derived growth factor (PDGF) (Akt activators) or activation of conventional/novel (c/n) protein kinase C (PKC) and 5' AMP-activated protein kinase (AMPK) all promote a rise in membrane GLUT4 in skeletal muscle and cultured cells.
287	17259386	Here we explore the hypothesis that AS160 is a molecular link among diverse signaling cascades converging on GLUT4 translocation.
288	17259386	PDGF and insulin increased AS160 phosphorylation in CHO-IR cells.
289	17259386	Stimuli that activate c/n PKC or AMPK also elevated AS160 phosphorylation.
290	17259386	We therefore examined if these signaling pathways engage AS160 to regulate GLUT4 traffic in muscle cells.
291	17259386	Nonphosphorylatable AS160 (4P-AS160) virtually abolished the net surface GLUT4myc gains elicited by insulin, PDGF, K(+) depolarization, or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside but partly, yet significantly, inhibited the effects of 4-phorbol-12-myristate-13-acetate.
292	17259386	RK-AS160 (GTPase-activating protein [GAP] inactive) or 4PRK-AS160 (GAP inactive, nonphosphorylatable) had no effect on surface GLUT4myc elicited by all stimuli.
293	17259386	Collectively, these results indicate that activation of Akt, c/n PKC, or alpha2-AMPK intersect at AS160 to regulate GLUT4 traffic, as well as highlight the potential of AS160 as a therapy target to increase muscle glucose uptake.
294	17259386	The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic.
295	17259386	Insulin-dependent phosphorylation of Akt target AS160 is required for GLUT4 translocation.
296	17259386	Insulin and platelet-derived growth factor (PDGF) (Akt activators) or activation of conventional/novel (c/n) protein kinase C (PKC) and 5' AMP-activated protein kinase (AMPK) all promote a rise in membrane GLUT4 in skeletal muscle and cultured cells.
297	17259386	Here we explore the hypothesis that AS160 is a molecular link among diverse signaling cascades converging on GLUT4 translocation.
298	17259386	PDGF and insulin increased AS160 phosphorylation in CHO-IR cells.
299	17259386	Stimuli that activate c/n PKC or AMPK also elevated AS160 phosphorylation.
300	17259386	We therefore examined if these signaling pathways engage AS160 to regulate GLUT4 traffic in muscle cells.
301	17259386	Nonphosphorylatable AS160 (4P-AS160) virtually abolished the net surface GLUT4myc gains elicited by insulin, PDGF, K(+) depolarization, or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside but partly, yet significantly, inhibited the effects of 4-phorbol-12-myristate-13-acetate.
302	17259386	RK-AS160 (GTPase-activating protein [GAP] inactive) or 4PRK-AS160 (GAP inactive, nonphosphorylatable) had no effect on surface GLUT4myc elicited by all stimuli.
303	17259386	Collectively, these results indicate that activation of Akt, c/n PKC, or alpha2-AMPK intersect at AS160 to regulate GLUT4 traffic, as well as highlight the potential of AS160 as a therapy target to increase muscle glucose uptake.
304	17259386	The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic.
305	17259386	Insulin-dependent phosphorylation of Akt target AS160 is required for GLUT4 translocation.
306	17259386	Insulin and platelet-derived growth factor (PDGF) (Akt activators) or activation of conventional/novel (c/n) protein kinase C (PKC) and 5' AMP-activated protein kinase (AMPK) all promote a rise in membrane GLUT4 in skeletal muscle and cultured cells.
307	17259386	Here we explore the hypothesis that AS160 is a molecular link among diverse signaling cascades converging on GLUT4 translocation.
308	17259386	PDGF and insulin increased AS160 phosphorylation in CHO-IR cells.
309	17259386	Stimuli that activate c/n PKC or AMPK also elevated AS160 phosphorylation.
310	17259386	We therefore examined if these signaling pathways engage AS160 to regulate GLUT4 traffic in muscle cells.
311	17259386	Nonphosphorylatable AS160 (4P-AS160) virtually abolished the net surface GLUT4myc gains elicited by insulin, PDGF, K(+) depolarization, or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside but partly, yet significantly, inhibited the effects of 4-phorbol-12-myristate-13-acetate.
312	17259386	RK-AS160 (GTPase-activating protein [GAP] inactive) or 4PRK-AS160 (GAP inactive, nonphosphorylatable) had no effect on surface GLUT4myc elicited by all stimuli.
313	17259386	Collectively, these results indicate that activation of Akt, c/n PKC, or alpha2-AMPK intersect at AS160 to regulate GLUT4 traffic, as well as highlight the potential of AS160 as a therapy target to increase muscle glucose uptake.
314	17259386	The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic.
315	17259386	Insulin-dependent phosphorylation of Akt target AS160 is required for GLUT4 translocation.
316	17259386	Insulin and platelet-derived growth factor (PDGF) (Akt activators) or activation of conventional/novel (c/n) protein kinase C (PKC) and 5' AMP-activated protein kinase (AMPK) all promote a rise in membrane GLUT4 in skeletal muscle and cultured cells.
317	17259386	Here we explore the hypothesis that AS160 is a molecular link among diverse signaling cascades converging on GLUT4 translocation.
318	17259386	PDGF and insulin increased AS160 phosphorylation in CHO-IR cells.
319	17259386	Stimuli that activate c/n PKC or AMPK also elevated AS160 phosphorylation.
320	17259386	We therefore examined if these signaling pathways engage AS160 to regulate GLUT4 traffic in muscle cells.
321	17259386	Nonphosphorylatable AS160 (4P-AS160) virtually abolished the net surface GLUT4myc gains elicited by insulin, PDGF, K(+) depolarization, or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside but partly, yet significantly, inhibited the effects of 4-phorbol-12-myristate-13-acetate.
322	17259386	RK-AS160 (GTPase-activating protein [GAP] inactive) or 4PRK-AS160 (GAP inactive, nonphosphorylatable) had no effect on surface GLUT4myc elicited by all stimuli.
323	17259386	Collectively, these results indicate that activation of Akt, c/n PKC, or alpha2-AMPK intersect at AS160 to regulate GLUT4 traffic, as well as highlight the potential of AS160 as a therapy target to increase muscle glucose uptake.
324	17259386	The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic.
325	17259386	Insulin-dependent phosphorylation of Akt target AS160 is required for GLUT4 translocation.
326	17259386	Insulin and platelet-derived growth factor (PDGF) (Akt activators) or activation of conventional/novel (c/n) protein kinase C (PKC) and 5' AMP-activated protein kinase (AMPK) all promote a rise in membrane GLUT4 in skeletal muscle and cultured cells.
327	17259386	Here we explore the hypothesis that AS160 is a molecular link among diverse signaling cascades converging on GLUT4 translocation.
328	17259386	PDGF and insulin increased AS160 phosphorylation in CHO-IR cells.
329	17259386	Stimuli that activate c/n PKC or AMPK also elevated AS160 phosphorylation.
330	17259386	We therefore examined if these signaling pathways engage AS160 to regulate GLUT4 traffic in muscle cells.
331	17259386	Nonphosphorylatable AS160 (4P-AS160) virtually abolished the net surface GLUT4myc gains elicited by insulin, PDGF, K(+) depolarization, or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside but partly, yet significantly, inhibited the effects of 4-phorbol-12-myristate-13-acetate.
332	17259386	RK-AS160 (GTPase-activating protein [GAP] inactive) or 4PRK-AS160 (GAP inactive, nonphosphorylatable) had no effect on surface GLUT4myc elicited by all stimuli.
333	17259386	Collectively, these results indicate that activation of Akt, c/n PKC, or alpha2-AMPK intersect at AS160 to regulate GLUT4 traffic, as well as highlight the potential of AS160 as a therapy target to increase muscle glucose uptake.
334	17259386	The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic.
335	17259386	Insulin-dependent phosphorylation of Akt target AS160 is required for GLUT4 translocation.
336	17259386	Insulin and platelet-derived growth factor (PDGF) (Akt activators) or activation of conventional/novel (c/n) protein kinase C (PKC) and 5' AMP-activated protein kinase (AMPK) all promote a rise in membrane GLUT4 in skeletal muscle and cultured cells.
337	17259386	Here we explore the hypothesis that AS160 is a molecular link among diverse signaling cascades converging on GLUT4 translocation.
338	17259386	PDGF and insulin increased AS160 phosphorylation in CHO-IR cells.
339	17259386	Stimuli that activate c/n PKC or AMPK also elevated AS160 phosphorylation.
340	17259386	We therefore examined if these signaling pathways engage AS160 to regulate GLUT4 traffic in muscle cells.
341	17259386	Nonphosphorylatable AS160 (4P-AS160) virtually abolished the net surface GLUT4myc gains elicited by insulin, PDGF, K(+) depolarization, or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside but partly, yet significantly, inhibited the effects of 4-phorbol-12-myristate-13-acetate.
342	17259386	RK-AS160 (GTPase-activating protein [GAP] inactive) or 4PRK-AS160 (GAP inactive, nonphosphorylatable) had no effect on surface GLUT4myc elicited by all stimuli.
343	17259386	Collectively, these results indicate that activation of Akt, c/n PKC, or alpha2-AMPK intersect at AS160 to regulate GLUT4 traffic, as well as highlight the potential of AS160 as a therapy target to increase muscle glucose uptake.
344	17259386	The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic.
345	17259386	Insulin-dependent phosphorylation of Akt target AS160 is required for GLUT4 translocation.
346	17259386	Insulin and platelet-derived growth factor (PDGF) (Akt activators) or activation of conventional/novel (c/n) protein kinase C (PKC) and 5' AMP-activated protein kinase (AMPK) all promote a rise in membrane GLUT4 in skeletal muscle and cultured cells.
347	17259386	Here we explore the hypothesis that AS160 is a molecular link among diverse signaling cascades converging on GLUT4 translocation.
348	17259386	PDGF and insulin increased AS160 phosphorylation in CHO-IR cells.
349	17259386	Stimuli that activate c/n PKC or AMPK also elevated AS160 phosphorylation.
350	17259386	We therefore examined if these signaling pathways engage AS160 to regulate GLUT4 traffic in muscle cells.
351	17259386	Nonphosphorylatable AS160 (4P-AS160) virtually abolished the net surface GLUT4myc gains elicited by insulin, PDGF, K(+) depolarization, or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside but partly, yet significantly, inhibited the effects of 4-phorbol-12-myristate-13-acetate.
352	17259386	RK-AS160 (GTPase-activating protein [GAP] inactive) or 4PRK-AS160 (GAP inactive, nonphosphorylatable) had no effect on surface GLUT4myc elicited by all stimuli.
353	17259386	Collectively, these results indicate that activation of Akt, c/n PKC, or alpha2-AMPK intersect at AS160 to regulate GLUT4 traffic, as well as highlight the potential of AS160 as a therapy target to increase muscle glucose uptake.
354	17259386	The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic.
355	17259386	Insulin-dependent phosphorylation of Akt target AS160 is required for GLUT4 translocation.
356	17259386	Insulin and platelet-derived growth factor (PDGF) (Akt activators) or activation of conventional/novel (c/n) protein kinase C (PKC) and 5' AMP-activated protein kinase (AMPK) all promote a rise in membrane GLUT4 in skeletal muscle and cultured cells.
357	17259386	Here we explore the hypothesis that AS160 is a molecular link among diverse signaling cascades converging on GLUT4 translocation.
358	17259386	PDGF and insulin increased AS160 phosphorylation in CHO-IR cells.
359	17259386	Stimuli that activate c/n PKC or AMPK also elevated AS160 phosphorylation.
360	17259386	We therefore examined if these signaling pathways engage AS160 to regulate GLUT4 traffic in muscle cells.
361	17259386	Nonphosphorylatable AS160 (4P-AS160) virtually abolished the net surface GLUT4myc gains elicited by insulin, PDGF, K(+) depolarization, or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside but partly, yet significantly, inhibited the effects of 4-phorbol-12-myristate-13-acetate.
362	17259386	RK-AS160 (GTPase-activating protein [GAP] inactive) or 4PRK-AS160 (GAP inactive, nonphosphorylatable) had no effect on surface GLUT4myc elicited by all stimuli.
363	17259386	Collectively, these results indicate that activation of Akt, c/n PKC, or alpha2-AMPK intersect at AS160 to regulate GLUT4 traffic, as well as highlight the potential of AS160 as a therapy target to increase muscle glucose uptake.
364	17327455	We examined whether obese type 2 diabetic subjects have impaired exercise stimulation of AMPK, at different signaling levels, spanning from the upstream kinase, LKB1, to the putative AMPK targets, AS160 and peroxisome proliferator-activated receptor coactivator (PGC)-1alpha, involved in glucose transport regulation and mitochondrial biogenesis, respectively.
365	17363741	Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity.
366	17363741	Elevated plasma levels of IL-6 are observed in insulin-resistant states.
367	17363741	Thus, IL-6 has also been suggested to promote insulin-mediated glucose utilization.
368	17363741	A 30-min pre-exposure to IL-6 did not affect insulin-stimulated glucose transport.
369	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).
370	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.
371	17363741	Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure.
372	17440174	Impairments in lipid metabolism were accompanied by defects in the Akt/AS160 signaling pathway.
373	17440174	The improvements to glucose and lipid metabolism observed with exercise training were associated with increased AMP-activated protein kinase alpha1 activity; increased expression of Akt1, peroxisome proliferator-activated receptor gamma coactivator 1, and GLUT4; and a decrease in AS160 expression.
374	17513702	Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS160.
375	17513702	Protein content of Akt1/2 (55 +/- 17%, P < 0.05), AS160 (25 +/- 8%, P = 0.08), GLUT4 (52 +/- 19%, P < 0.001), hexokinase 2 (HK2) (197 +/- 40%, P < 0.001), and insulin-responsive aminopeptidase (65 +/- 15%, P < 0.001) increased in muscle in response to training.
376	17513702	During hyperinsulinemia, activities of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-K) (P < 0.005), Akt1 (P < 0.05), Akt2 (P < 0.005), and glycogen synthase (GS) (percent I-form, P < 0.05) increased similarly in both trained and untrained muscle, consistent with increased phosphorylation of Akt Thr(308), Akt Ser(473), AS160, glycogen synthase kinase (GSK)-3alpha Ser(21), and GSK-3beta Ser(9) and decreased phosphorylation of GS site 3a+b (all P < 0.005).
377	17513702	Interestingly, training improved insulin action on thigh blood flow, and, furthermore, in both basal and insulin-stimulated muscle tissue, activities of Akt1 and GS and phosphorylation of AS160 increased with training (all P < 0.05).
378	17513702	In contrast, training reduced IRS-1-associated PI3-K activity (P < 0.05) in both basal and insulin-stimulated muscle tissue.
379	17717281	Calmodulin-binding domain of AS160 regulates contraction- but not insulin-stimulated glucose uptake in skeletal muscle.
380	17785505	Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation.
381	17785505	Despite these changes, there was no decrease in the phosphorylation state of multiple insulin signaling intermediates [insulin receptor, Akt, AS160 (Akt substrate of 160 kDa), glycogen synthase kinase-3beta] over the same time course.
382	17785505	Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation.
383	17785505	Despite these changes, there was no decrease in the phosphorylation state of multiple insulin signaling intermediates [insulin receptor, Akt, AS160 (Akt substrate of 160 kDa), glycogen synthase kinase-3beta] over the same time course.
384	17977950	Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment.
385	18171435	Evidence now suggests that the improvements in insulin sensitivity associated with exercise training are also related to changes in the expression and/or activity of proteins involved in insulin signal transduction in skeletal muscle such as the AMP-activated protein kinase (AMPK) and the protein kinase B (Akt) substrate AS160.
386	18276596	Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle.
387	18276596	The Akt substrate of 160 kDa (AS160) is phosphorylated on Akt substrate (PAS) motifs in response to insulin and contraction in skeletal muscle, regulating glucose uptake.
388	18276596	By immunoprecipitation and mass spectrometry, we identified this protein as the AS160 paralog TBC1D1, an obesity candidate gene regulating GLUT4 translocation in adipocytes.
389	18276596	In vivo stimulation by insulin, contraction, and the AMP-activated protein kinase (AMPK) activator AICAR increased TBC1D1 PAS phosphorylation.
390	18276596	Using mass spectrometry on TBC1D1 from mouse skeletal muscle, we identified several novel phosphorylation sites on TBC1D1 and found the majority were consensus or near consensus sites for AMPK.
391	18276596	Purified Akt and AMPK phosphorylated TBC1D1 in vitro, and AMPK, but not Akt, reduced TBC1D1 electrophoretic mobility.
392	18276596	TBC1D1 is a major PAS immunoreactive protein in skeletal muscle that is phosphorylated in vivo by insulin, AICAR, and contraction.
393	18276596	Both Akt and AMPK phosphorylate TBC1D1, but AMPK may be the more robust regulator.
394	18276596	Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle.
395	18276596	The Akt substrate of 160 kDa (AS160) is phosphorylated on Akt substrate (PAS) motifs in response to insulin and contraction in skeletal muscle, regulating glucose uptake.
396	18276596	By immunoprecipitation and mass spectrometry, we identified this protein as the AS160 paralog TBC1D1, an obesity candidate gene regulating GLUT4 translocation in adipocytes.
397	18276596	In vivo stimulation by insulin, contraction, and the AMP-activated protein kinase (AMPK) activator AICAR increased TBC1D1 PAS phosphorylation.
398	18276596	Using mass spectrometry on TBC1D1 from mouse skeletal muscle, we identified several novel phosphorylation sites on TBC1D1 and found the majority were consensus or near consensus sites for AMPK.
399	18276596	Purified Akt and AMPK phosphorylated TBC1D1 in vitro, and AMPK, but not Akt, reduced TBC1D1 electrophoretic mobility.
400	18276596	TBC1D1 is a major PAS immunoreactive protein in skeletal muscle that is phosphorylated in vivo by insulin, AICAR, and contraction.
401	18276596	Both Akt and AMPK phosphorylate TBC1D1, but AMPK may be the more robust regulator.
402	18276765	Rab GTPase-activating protein AS160 is a major downstream effector of protein kinase B/Akt signaling in pancreatic beta-cells.
403	18477703	Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic.
404	18477703	Vesicular traffic of the glucose transporter GLUT4 occurs in response to insulin, muscle contraction, and metabolic stimuli that lead to changes in the energy status of the cell.
405	18477703	The Rab-GTPase-activating proteins AS160 and TBC1D1 have now emerged as strong candidates to fill this void.
406	18477703	We examine the current state of a hypothesis that suggests that phosphorylation of the Rab-GTPase-activating proteins leads to increased GTP loading of Rab proteins on GLUT4 vesicles and subsequently to increased interaction with Rab effectors that control GLUT4 vesicle translocation.
407	18477703	Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic.
408	18477703	Vesicular traffic of the glucose transporter GLUT4 occurs in response to insulin, muscle contraction, and metabolic stimuli that lead to changes in the energy status of the cell.
409	18477703	The Rab-GTPase-activating proteins AS160 and TBC1D1 have now emerged as strong candidates to fill this void.
410	18477703	We examine the current state of a hypothesis that suggests that phosphorylation of the Rab-GTPase-activating proteins leads to increased GTP loading of Rab proteins on GLUT4 vesicles and subsequently to increased interaction with Rab effectors that control GLUT4 vesicle translocation.
411	18931681	Here we identify a SJL-specific mutation in the Tbc1d1 gene that results in a truncated protein lacking the TBC Rab-GTPase-activating protein domain.
412	18931681	TBC1D1, which has been recently linked to human obesity, is related to the insulin signaling protein AS160 and is predominantly expressed in skeletal muscle.
413	19190259	We demonstrated previously that, in healthy young men, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR) stimulates human muscle 2-deoxyglucose (2DG) uptake without detectable activation of muscle AMP-activated protein kinase (AMPK) but with extracellular-regulated kinase 1/2 (ERK1/2) activation.
414	19190259	We determined 1) 2DG uptake, 2) total AMPKalpha activity, AMPK, acetyl-CoA carboxylase (ACC), and AS160 phosphorylation, and 3) ERK1/2 phosphorylation.
415	19190259	At 3-h AMPK activity and AMPK, ACC and AS160 phosphorylation were unchanged, but ERK1/2 phosphorylation increased at both AICAR doses.
416	19190259	We demonstrated previously that, in healthy young men, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR) stimulates human muscle 2-deoxyglucose (2DG) uptake without detectable activation of muscle AMP-activated protein kinase (AMPK) but with extracellular-regulated kinase 1/2 (ERK1/2) activation.
417	19190259	We determined 1) 2DG uptake, 2) total AMPKalpha activity, AMPK, acetyl-CoA carboxylase (ACC), and AS160 phosphorylation, and 3) ERK1/2 phosphorylation.
418	19190259	At 3-h AMPK activity and AMPK, ACC and AS160 phosphorylation were unchanged, but ERK1/2 phosphorylation increased at both AICAR doses.
419	19276091	Targeted disruption of ROCK1 causes insulin resistance in vivo.
420	19276091	Rho-kinase (ROCK) isoforms have been shown to participate in insulin signaling and glucose metabolism in cultured cell lines.
421	19276091	To investigate the physiological role of ROCK1 in the regulation of whole body glucose homeostasis and insulin sensitivity in vivo, we studied mice with global disruption of ROCK1.
422	19276091	Interestingly, ROCK1 gene ablation caused a significant increase in glucose-induced insulin secretion, leading to hyperinsulinemia.
423	19276091	To determine the mechanism(s) by which deletion of ROCK1 causes insulin resistance, we measured the ability of insulin to activate phosphatidylinositol 3-kinase and multiple distal pathways in skeletal muscle.
424	19276091	Insulin-stimulated phosphatidylinositol 3-kinase activity associated with IRS-1 or phospho-tyrosine was also reduced approximately 40% without any alteration in tyrosine phosphorylation of insulin receptor in skeletal muscle.
425	19276091	Insulin-induced phosphorylation of Akt, AS160, S6K, and S6 was also decreased in skeletal muscle.
426	19276091	These data suggest that ROCK1 deficiency causes systemic insulin resistance by impairing insulin signaling in skeletal muscle.
427	19276091	Thus, our results identify ROCK1 as a novel regulator of glucose homeostasis and insulin sensitivity in vivo, which could lead to new treatment approaches for obesity and type 2 diabetes.
428	19532121	RUVBL2, a novel AS160-binding protein, regulates insulin-stimulated GLUT4 translocation.
429	19532121	In fat and muscle cells, insulin-stimulated glucose uptake is mainly mediated by glucose transporter 4 (GLUT4), which translocates from intracellular compartments to the cell surface in response to insulin stimulation.
430	19532121	AS160 is one of the substrates of Akt and plays important roles in insulin-regulated GLUT4 translocation.
431	19532121	In this study, RuvB-like protein 2 (RUVBL2) is identified as a new AS160-binding protein using mammalian tandem affinity purification (TAP) combined with mass spectrometry.
432	19532121	Depletion of RUVBL2 in adipocytes inhibits insulin-stimulated GLUT4 translocation and glucose uptake through reducing insulin-stimulated AS160 phosphorylation.
433	19532121	These data suggest that RUVBL2 plays an important role in insulin-stimulated GLUT4 translocation through its interaction with AS160.
434	19532121	RUVBL2, a novel AS160-binding protein, regulates insulin-stimulated GLUT4 translocation.
435	19532121	In fat and muscle cells, insulin-stimulated glucose uptake is mainly mediated by glucose transporter 4 (GLUT4), which translocates from intracellular compartments to the cell surface in response to insulin stimulation.
436	19532121	AS160 is one of the substrates of Akt and plays important roles in insulin-regulated GLUT4 translocation.
437	19532121	In this study, RuvB-like protein 2 (RUVBL2) is identified as a new AS160-binding protein using mammalian tandem affinity purification (TAP) combined with mass spectrometry.
438	19532121	Depletion of RUVBL2 in adipocytes inhibits insulin-stimulated GLUT4 translocation and glucose uptake through reducing insulin-stimulated AS160 phosphorylation.
439	19532121	These data suggest that RUVBL2 plays an important role in insulin-stimulated GLUT4 translocation through its interaction with AS160.
440	19690174	Silencing mitogen-activated protein 4 kinase 4 (MAP4K4) protects beta cells from tumor necrosis factor-alpha-induced decrease of IRS-2 and inhibition of glucose-stimulated insulin secretion.
441	19690174	In healthy humans, TNF-alpha infusion induces skeletal muscle insulin resistance.
442	19690174	Human and rat primary beta cells were sorted by FACS and cultured for 24 h +/- 20 ng/ml TNF-alpha to explore the impact on apoptosis, proliferation, and short-term insulin secretion (1 h, 2.8 mm glucose followed by 1 h, 16.7 mm glucose at the end of the 24-h culture period) as well as key signaling protein phosphorylation and expression.
443	19690174	Prior exposure to TNF-alpha for 24 h inhibits glucose-stimulated insulin secretion from primary beta cells.
444	19690174	This is associated with a decrease in glucose-stimulated phosphorylation of key proteins in the insulin signaling pathway including Akt, AS160, and other Akt substrates, ERK as well as the insulin receptor.
445	19690174	Strikingly, TNF-alpha treatment decreased IRS-2 protein level by 46 +/- 7% versus control, although mRNA expression was unchanged.
446	19690174	While TNF-alpha treatment increased MAP4K4 mRNA expression by 33 +/- 5%, knockdown of MAP4K4 by siRNA-protected beta cells against the detrimental effects of TNF-alpha on both insulin secretion and signaling.
447	19690174	We thus identify MAP4K4 as a key upstream mediator of TNF-alpha action on the beta cell, making it a potential therapeutic target for preservation of beta cell function in type 2 diabetes.
448	19923418	Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle.
449	19923418	TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle.
450	19923418	Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization.
451	19923418	The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation.
452	19923418	However, the 5'-AMP-activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites.
453	19923418	Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4.
454	19923418	Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro.
455	19923418	Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli.
456	19923418	S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle.
457	19923418	Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle.
458	19923418	TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle.
459	19923418	Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization.
460	19923418	The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation.
461	19923418	However, the 5'-AMP-activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites.
462	19923418	Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4.
463	19923418	Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro.
464	19923418	Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli.
465	19923418	S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle.
466	19923418	Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle.
467	19923418	TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle.
468	19923418	Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization.
469	19923418	The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation.
470	19923418	However, the 5'-AMP-activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites.
471	19923418	Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4.
472	19923418	Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro.
473	19923418	Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli.
474	19923418	S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle.
475	19923418	Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle.
476	19923418	TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle.
477	19923418	Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization.
478	19923418	The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation.
479	19923418	However, the 5'-AMP-activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites.
480	19923418	Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4.
481	19923418	Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro.
482	19923418	Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli.
483	19923418	S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle.
484	19923418	Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle.
485	19923418	TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle.
486	19923418	Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization.
487	19923418	The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation.
488	19923418	However, the 5'-AMP-activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites.
489	19923418	Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4.
490	19923418	Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro.
491	19923418	Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli.
492	19923418	S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle.
493	19923418	Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle.
494	19923418	TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle.
495	19923418	Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization.
496	19923418	The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation.
497	19923418	However, the 5'-AMP-activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites.
498	19923418	Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4.
499	19923418	Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro.
500	19923418	Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli.
501	19923418	S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle.
502	19923418	Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle.
503	19923418	TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle.
504	19923418	Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization.
505	19923418	The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation.
506	19923418	However, the 5'-AMP-activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites.
507	19923418	Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4.
508	19923418	Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro.
509	19923418	Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli.
510	19923418	S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle.
511	20215576	CaMKII regulates contraction- but not insulin-induced glucose uptake in mouse skeletal muscle.
512	20215576	Studies using chemical inhibitors have suggested that the Ca(2+)-sensitive serine/threonine kinase Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of both insulin- and contraction-stimulated glucose uptake in skeletal muscle.
513	20215576	We sought to determine whether specific inhibition of CaMKII impairs insulin- and/or contraction-induced glucose uptake in mouse skeletal muscle.
514	20215576	After 1 wk, muscles were assessed for peptide expression, CaMK activity, insulin- and contraction-induced 2-[(3)H]deoxyglucose uptake, glycogen concentrations, and changes in intracellular signaling proteins.
515	20215576	The CaMKII inhibitory peptide did not alter expression of the glucose transporter GLUT4 and did not impair contraction-induced increases in the phosphorylation of AMP-activated protein kinase (Thr(172)) or TBC1D1/TBC1D4 on phospho-Akt substrate sites.
516	20215576	These results demonstrate that CaMKII does not regulate insulin-stimulated glucose uptake in skeletal muscle.
517	20839494	Akt, AS160, metabolic risk factors and aerobic fitness in middle-aged women.
518	20938636	Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training.
519	21454505	Crystal structures of human TBC1D1 and TBC1D4 (AS160) RabGTPase-activating protein (RabGAP) domains reveal critical elements for GLUT4 translocation.
520	21454505	We have solved the x-ray crystal structures of the RabGAP domains of human TBC1D1 and human TBC1D4 (AS160), at 2.2 and 3.5 Å resolution, respectively.
521	21454505	Like the yeast Gyp1p RabGAP domain, whose structure was solved previously in complex with mouse Rab33B, the human TBC1D1 and TBC1D4 domains both have 16 α-helices and no β-sheet elements.
522	21454505	We hypothesized that biologically relevant RabGAP/Rab partners utilize additional contacts not described in the yeast Gyp1p/mouse Rab33B structure, which we predicted using our two new human TBC1D1 and TBC1D4 structures.
523	21454505	Ala substitution of TBC1D1 Met(930), corresponding to a residue outside of the Gyp1p/Rab33B contact, substantially reduced catalytic activity.
524	21454505	Substitutions with lowest RabGAP activity, including catalytically dead RK and Met(930) and Leu(1019) predicted to perturb Rab binding, confirmed that biological activity requires contacts between cognate RabGAPs and Rabs beyond those in the yeast Gyp1p RabGAP/mouse Rab33B structure.
525	21454505	Crystal structures of human TBC1D1 and TBC1D4 (AS160) RabGTPase-activating protein (RabGAP) domains reveal critical elements for GLUT4 translocation.
526	21454505	We have solved the x-ray crystal structures of the RabGAP domains of human TBC1D1 and human TBC1D4 (AS160), at 2.2 and 3.5 Å resolution, respectively.
527	21454505	Like the yeast Gyp1p RabGAP domain, whose structure was solved previously in complex with mouse Rab33B, the human TBC1D1 and TBC1D4 domains both have 16 α-helices and no β-sheet elements.
528	21454505	We hypothesized that biologically relevant RabGAP/Rab partners utilize additional contacts not described in the yeast Gyp1p/mouse Rab33B structure, which we predicted using our two new human TBC1D1 and TBC1D4 structures.
529	21454505	Ala substitution of TBC1D1 Met(930), corresponding to a residue outside of the Gyp1p/Rab33B contact, substantially reduced catalytic activity.
530	21454505	Substitutions with lowest RabGAP activity, including catalytically dead RK and Met(930) and Leu(1019) predicted to perturb Rab binding, confirmed that biological activity requires contacts between cognate RabGAPs and Rabs beyond those in the yeast Gyp1p RabGAP/mouse Rab33B structure.
531	21454505	Crystal structures of human TBC1D1 and TBC1D4 (AS160) RabGTPase-activating protein (RabGAP) domains reveal critical elements for GLUT4 translocation.
532	21454505	We have solved the x-ray crystal structures of the RabGAP domains of human TBC1D1 and human TBC1D4 (AS160), at 2.2 and 3.5 Å resolution, respectively.
533	21454505	Like the yeast Gyp1p RabGAP domain, whose structure was solved previously in complex with mouse Rab33B, the human TBC1D1 and TBC1D4 domains both have 16 α-helices and no β-sheet elements.
534	21454505	We hypothesized that biologically relevant RabGAP/Rab partners utilize additional contacts not described in the yeast Gyp1p/mouse Rab33B structure, which we predicted using our two new human TBC1D1 and TBC1D4 structures.
535	21454505	Ala substitution of TBC1D1 Met(930), corresponding to a residue outside of the Gyp1p/Rab33B contact, substantially reduced catalytic activity.
536	21454505	Substitutions with lowest RabGAP activity, including catalytically dead RK and Met(930) and Leu(1019) predicted to perturb Rab binding, confirmed that biological activity requires contacts between cognate RabGAPs and Rabs beyond those in the yeast Gyp1p RabGAP/mouse Rab33B structure.
537	21454505	Crystal structures of human TBC1D1 and TBC1D4 (AS160) RabGTPase-activating protein (RabGAP) domains reveal critical elements for GLUT4 translocation.
538	21454505	We have solved the x-ray crystal structures of the RabGAP domains of human TBC1D1 and human TBC1D4 (AS160), at 2.2 and 3.5 Å resolution, respectively.
539	21454505	Like the yeast Gyp1p RabGAP domain, whose structure was solved previously in complex with mouse Rab33B, the human TBC1D1 and TBC1D4 domains both have 16 α-helices and no β-sheet elements.
540	21454505	We hypothesized that biologically relevant RabGAP/Rab partners utilize additional contacts not described in the yeast Gyp1p/mouse Rab33B structure, which we predicted using our two new human TBC1D1 and TBC1D4 structures.
541	21454505	Ala substitution of TBC1D1 Met(930), corresponding to a residue outside of the Gyp1p/Rab33B contact, substantially reduced catalytic activity.
542	21454505	Substitutions with lowest RabGAP activity, including catalytically dead RK and Met(930) and Leu(1019) predicted to perturb Rab binding, confirmed that biological activity requires contacts between cognate RabGAPs and Rabs beyond those in the yeast Gyp1p RabGAP/mouse Rab33B structure.
543	21454697	Insulin-stimulated GLUT4 protein translocation in adipocytes requires the Rab10 guanine nucleotide exchange factor Dennd4C.
544	21454697	Insulin-stimulated translocation of the glucose transporter GLUT4 to the cell surface in fat and muscle cells is the basis for insulin-stimulated glucose transport.
545	21454697	Insulin-elicited phosphorylation of the GTPase-activating protein TBC1D4 (AS160) suppresses its activity toward Rab10 and thereby leads to an increase in the GTP-bound form of Rab10, which in turn triggers movement of vesicles containing GLUT4 to the plasma membrane and their fusion with the membrane.
546	21454697	This process is expected to require the participation of a guanine nucleotide exchange factor (GEF) to generate the GTP-bound form of Rab10, but this GEF has not hitherto been identified.
547	21454697	The present study identifies Dennd4C, a recently described GEF for Rab10, as the primary GEF required for GLUT4 translocation.
548	21454697	Knockdown of Dennd4C markedly inhibited GLUT4 translocation, and ectopic expression of Dennd4C slightly stimulated it.
549	21454697	Dennd4C was found in isolated GLUT4 vesicles.
550	21505148	Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1.
551	21505148	Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation.
552	21505148	In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood.
553	21505148	In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle.
554	21505148	Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser(711) (AMPK), TBC1D1 Ser(231) (AMPK), TBC1D1 Ser(660) (AMPK), TBC1D1 Ser(700) (AMPK), and TBC1D1 Thr(590) (Akt).
555	21505148	Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700).
556	21505148	Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation.
557	21505148	These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.
558	21505148	Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1.
559	21505148	Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation.
560	21505148	In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood.
561	21505148	In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle.
562	21505148	Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser(711) (AMPK), TBC1D1 Ser(231) (AMPK), TBC1D1 Ser(660) (AMPK), TBC1D1 Ser(700) (AMPK), and TBC1D1 Thr(590) (Akt).
563	21505148	Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700).
564	21505148	Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation.
565	21505148	These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.
566	21505148	Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1.
567	21505148	Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation.
568	21505148	In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood.
569	21505148	In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle.
570	21505148	Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser(711) (AMPK), TBC1D1 Ser(231) (AMPK), TBC1D1 Ser(660) (AMPK), TBC1D1 Ser(700) (AMPK), and TBC1D1 Thr(590) (Akt).
571	21505148	Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700).
572	21505148	Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation.
573	21505148	These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.
574	21505148	Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1.
575	21505148	Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation.
576	21505148	In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood.
577	21505148	In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle.
578	21505148	Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser(711) (AMPK), TBC1D1 Ser(231) (AMPK), TBC1D1 Ser(660) (AMPK), TBC1D1 Ser(700) (AMPK), and TBC1D1 Thr(590) (Akt).
579	21505148	Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700).
580	21505148	Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation.
581	21505148	These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.
582	21505148	Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1.
583	21505148	Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation.
584	21505148	In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood.
585	21505148	In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle.
586	21505148	Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser(711) (AMPK), TBC1D1 Ser(231) (AMPK), TBC1D1 Ser(660) (AMPK), TBC1D1 Ser(700) (AMPK), and TBC1D1 Thr(590) (Akt).
587	21505148	Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700).
588	21505148	Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation.
589	21505148	These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.
590	21505148	Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1.
591	21505148	Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation.
592	21505148	In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood.
593	21505148	In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle.
594	21505148	Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser(711) (AMPK), TBC1D1 Ser(231) (AMPK), TBC1D1 Ser(660) (AMPK), TBC1D1 Ser(700) (AMPK), and TBC1D1 Thr(590) (Akt).
595	21505148	Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700).
596	21505148	Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation.
597	21505148	These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.
598	21505148	Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1.
599	21505148	Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation.
600	21505148	In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood.
601	21505148	In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle.
602	21505148	Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser(711) (AMPK), TBC1D1 Ser(231) (AMPK), TBC1D1 Ser(660) (AMPK), TBC1D1 Ser(700) (AMPK), and TBC1D1 Thr(590) (Akt).
603	21505148	Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700).
604	21505148	Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation.
605	21505148	These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.
606	21505148	Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1.
607	21505148	Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation.
608	21505148	In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood.
609	21505148	In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle.
610	21505148	Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser(711) (AMPK), TBC1D1 Ser(231) (AMPK), TBC1D1 Ser(660) (AMPK), TBC1D1 Ser(700) (AMPK), and TBC1D1 Thr(590) (Akt).
611	21505148	Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700).
612	21505148	Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation.
613	21505148	These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.
614	22396207	Loss of AMP-activated protein kinase-α2 impairs the insulin-sensitizing effect of calorie restriction in skeletal muscle.
615	22396207	Whether the well-known metabolic switch AMP-activated protein kinase (AMPK) is involved in the insulin-sensitizing effect of calorie restriction (CR) is unclear.
616	22396207	In this study, we investigated the role of AMPK in the insulin-sensitizing effect of CR in skeletal muscle.
617	22396207	Furthermore, CR-induced activation of Akt-TBC1D1/TBC1D4 signaling, inhibition of mammalian target of rapamycin-S6K1-insulin receptor substrate-1 pathway, and induction of nicotinamide phosphoribosyltransferase-NAD(+)-sirtuin-1 cascade were remarkably impaired in AMPK-α2(-/-) mice.
618	22396207	CR serum increased stability of AMPK-α2 protein via inhibiting the X chromosome-linked ubiquitin-specific protease 9-mediated ubiquitylation of AMPK-α2.
619	22396207	Our results suggest that AMPK may be modulated by CR in a ubiquitylation-dependent manner and acts as a chief dictator for the insulin-sensitizing effects of CR in skeletal muscle.
620	22482906	To enhance glucose uptake into muscle and fat cells, insulin stimulates the translocation of GLUT4 glucose transporters from intracellular membranes to the cell surface.
621	22482906	Insulin signals through AS160/Tbc1D4 and Tbc1D1 to modulate Rab GTPases and through the Rho GTPase TC10α to act on other targets.
622	22482906	In unstimulated cells, GLUT4 is incorporated into specialized storage vesicles containing IRAP, LRP1, sortilin, and VAMP2, which are sequestered by TUG, Ubc9, and other proteins.
623	22773877	Lrictor(KO) mice had defects in insulin-stimulated Akt Ser-473 and Thr-308 phosphorylation, leading to decreased phosphorylation of Akt substrates FoxO, GSK-3β, PRAS40, AS160, and Tsc2.
624	22773877	Lrictor(KO) mice also manifest defects in insulin-activated mTORC1 activity, evidenced by decreased S6 kinase and Lipin1 phosphorylation.
625	22773877	Thus, we have identified an Akt-independent relay from mTORC2 to hepatic lipogenesis that separates the effects of insulin on glucose and lipid metabolism.
626	22851577	Exercise alleviates lipid-induced insulin resistance in human skeletal muscle-signaling interaction at the level of TBC1 domain family member 4.
627	22851577	We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle.
628	22851577	Insulin increased phosphorylation of TBC1D1/4.
629	22851577	In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation.
630	22851577	The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation.
631	22851577	Exercise alleviates lipid-induced insulin resistance in human skeletal muscle-signaling interaction at the level of TBC1 domain family member 4.
632	22851577	We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle.
633	22851577	Insulin increased phosphorylation of TBC1D1/4.
634	22851577	In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation.
635	22851577	The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation.
636	22851577	Exercise alleviates lipid-induced insulin resistance in human skeletal muscle-signaling interaction at the level of TBC1 domain family member 4.
637	22851577	We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle.
638	22851577	Insulin increased phosphorylation of TBC1D1/4.
639	22851577	In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation.
640	22851577	The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation.
641	23007523	Aldosterone treatment impaired the rate of glucose uptake, oxidation, and insulin signal transduction in the gastrocnemius muscle through defective expression of IR, IRS-1, Akt, AS160, and GLUT4 genes.
642	23007523	Phosphorylation of IRS-1, β-arrestin-2, and Akt was also reduced in a dose-dependent manner.
643	23045393	The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.
644	23045393	The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes.
645	23045393	Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect.
646	23045393	The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila.
647	23045393	The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation.
648	23045393	Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity.
649	23045393	The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.
650	23045393	The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes.
651	23045393	Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect.
652	23045393	The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila.
653	23045393	The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation.
654	23045393	Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity.
655	23045393	The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.
656	23045393	The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes.
657	23045393	Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect.
658	23045393	The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila.
659	23045393	The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation.
660	23045393	Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity.
661	23045393	The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.
662	23045393	The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes.
663	23045393	Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect.
664	23045393	The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila.
665	23045393	The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation.
666	23045393	Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity.
667	23045393	The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.
668	23045393	The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes.
669	23045393	Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect.
670	23045393	The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila.
671	23045393	The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation.
672	23045393	Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity.
673	23045393	The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.
674	23045393	The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes.
675	23045393	Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect.
676	23045393	The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila.
677	23045393	The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation.
678	23045393	Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity.
679	23272147	Effects of exercise on AMPK signaling and downstream components to PI3K in rat with type 2 diabetes.
680	23272147	We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and downstream components of phosphatidylinositol 3-kinase (PI3K) signaling pathways in the soleus.
681	23272147	Interestingly, chronic and acute exercise reduced blood glucose, increased phosphorylation and expression of AMPKα1/2 and the isoforms AMPKα1 and AMPKα2, and decreased phosphorylation and expression of AMPK substrate, acetyl CoA carboxylase (ACC).
682	23272147	Chronic exercise upregulated phosphorylation and expression of AMPK upstream kinase, LKB1.
683	23272147	Additionally, exercise also increased protein kinase B (PKB)/Akt1, Akt2 and GLUT4 expression, but AS160 protein expression was unchanged.
684	23272147	Chronic exercise elevated Akt (Thr(308)) and (Ser(473)) and AS160 phosphorylation.
685	23272147	These results indicate that both chronic and acute exercise influence the phosphorylation and expression of components of the AMPK and downstream to PIK3 (aPKC, Akt), and improve GLUT4 trafficking in skeletal muscle.
686	23272147	Effects of exercise on AMPK signaling and downstream components to PI3K in rat with type 2 diabetes.
687	23272147	We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and downstream components of phosphatidylinositol 3-kinase (PI3K) signaling pathways in the soleus.
688	23272147	Interestingly, chronic and acute exercise reduced blood glucose, increased phosphorylation and expression of AMPKα1/2 and the isoforms AMPKα1 and AMPKα2, and decreased phosphorylation and expression of AMPK substrate, acetyl CoA carboxylase (ACC).
689	23272147	Chronic exercise upregulated phosphorylation and expression of AMPK upstream kinase, LKB1.
690	23272147	Additionally, exercise also increased protein kinase B (PKB)/Akt1, Akt2 and GLUT4 expression, but AS160 protein expression was unchanged.
691	23272147	Chronic exercise elevated Akt (Thr(308)) and (Ser(473)) and AS160 phosphorylation.
692	23272147	These results indicate that both chronic and acute exercise influence the phosphorylation and expression of components of the AMPK and downstream to PIK3 (aPKC, Akt), and improve GLUT4 trafficking in skeletal muscle.
693	23428406	Inhibitors analyses revealed that F015-induced glucose uptake was dependent on the activation of phosphatidylinositol-3-kinase (PI-3-K) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), while independent to the activation of 5'AMP-activated kinase (AMPK).
694	23428406	F015 significantly increased the phosphorylation of AKT, AS160 and ERK1/2, account for the augmented glucose transport capacity in L6 myotubes.
695	23704966	Plasma LPS (r = -0.46, P = 0.005) and LBP (r = -0.49, P = 0.005) concentrations negatively correlated with muscle insulin sensitivity (M).
696	23704966	In human myotubes, LPS increased JNK phosphorylation and MCP-1 and IL-6 gene expression.
697	23704966	This inflammatory response led to reduced insulin-stimulated IRS-1, Akt and AS160 phosphorylation and impaired glucose transport.
698	23704966	Both pharmacologic blockade of TLR4 with TAK-242, and TLR4 gene silencing, suppressed the inflammatory response and insulin resistance caused by LPS in human muscle cells.
699	23704966	Taken together, these findings suggest that elevations in plasma LPS concentration found in obese and T2DM subjects could play a role in the pathogenesis of insulin resistance and that antagonists of TLR4 may improve insulin action in these individuals.
700	23752133	Insulin stimulation regulates AS160 and TBC1D1 phosphorylation sites in human skeletal muscle.
701	23928114	We used C2C12 skeletal muscle cells to examine the direct effect of fetuin-A on 2-deoxyglucose uptake, insulin signaling [phosphorylation of Akt and AS160 (pAkt and pAS160, respectively)], and glucose transporter-4 (GLUT-4) translocation.
702	23928114	Furthermore, circulating fetuin-A was decreased by 11% (4.2 ± 03 vs. 3.6 ± 0.2 nM; P < 0.02), and this change correlated with reduced insulin resistance (r = 0.62; P < 0.04) and glucose AUC (r = 0.58; P < 0.04).
703	23928114	In vitro experiments revealed that fetuin-A decreased skeletal muscle glucose uptake by downregulating pAkt and pAS160 and subsequent GLUT-4 translocation to the plasma membrane.
704	23928114	Together, our findings highlight a role for fetuin-A in skeletal muscle insulin resistance and suggest that part of the exercise-induced improvement in glucose tolerance in patients with NAFLD may be due to lowering fetuin-A.