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Gene Information

Gene symbol: PRKAA2

Gene name: protein kinase, AMP-activated, alpha 2 catalytic subunit

HGNC ID: 9377

Synonyms: AMPK, AMPKa2

Related Genes

#	Gene Symbol	Number of hits
1	ACACA	1 hits
2	ACACB	1 hits
3	ACADL	1 hits
4	ACADM	1 hits
5	ADIPOQ	1 hits
6	ADIPOR1	1 hits
7	ADIPOR2	1 hits
8	AK2	1 hits
9	AKT1	1 hits
10	ALB	1 hits
11	ANPEP	1 hits
12	AR	1 hits
13	ATIC	1 hits
14	CAMK2G	1 hits
15	CAMKK2	1 hits
16	CAV1	1 hits
17	CAV3	1 hits
18	COX4I1	1 hits
19	COX8B	1 hits
20	CREB1	1 hits
21	CRTC2	1 hits
22	EIF2AK4	1 hits
23	EPHB2	1 hits
24	ERAL1	1 hits
25	ESR2	1 hits
26	FGF21	1 hits
27	FOS	1 hits
28	GIP	1 hits
29	GPAM	1 hits
30	GRP	1 hits
31	HDAC5	1 hits
32	HIF1A	1 hits
33	IGF1	1 hits
34	IKBKB	1 hits
35	IL10	1 hits
36	IL1B	1 hits
37	IL6	1 hits
38	IL8	1 hits
39	INS	1 hits
40	INSR	1 hits
41	IRS1	1 hits
42	JUN	1 hits
43	LEP	1 hits
44	LEPR	1 hits
45	LIPE	1 hits
46	LTF	1 hits
47	MAP3K14	1 hits
48	MAPK1	1 hits
49	MAPK14	1 hits
50	MAPK3	1 hits
51	MAPK8	1 hits
52	MARK2	1 hits
53	MCTS1	1 hits
54	MLYCD	1 hits
55	MMEL1	1 hits
56	MYEF2	1 hits
57	NFE2L2	1 hits
58	NOS2A	1 hits
59	NOS3	1 hits
60	NOX4	1 hits
61	NOX5	1 hits
62	NP	1 hits
63	NR0B2	1 hits
64	NRF1	1 hits
65	NRIP1	1 hits
66	NUAK2	1 hits
67	ORAI1	1 hits
68	PASK	1 hits
69	PCK2	1 hits
70	PER2	1 hits
71	PGC	1 hits
72	PI3	1 hits
73	PIK3CA	1 hits
74	PIK3CG	1 hits
75	PLK1	1 hits
76	PPARG	1 hits
77	PPARGC1A	1 hits
78	PPM2C	1 hits
79	PRKAA1	1 hits
80	PRKAB1	1 hits
81	PRKAB2	1 hits
82	PRKAG3	1 hits
83	PRKAR2A	1 hits
84	PRKD1	1 hits
85	PTPN1	1 hits
86	RB1	1 hits
87	RHEB	1 hits
88	RORC	1 hits
89	RPS6KB1	1 hits
90	RUNX2	1 hits
91	SCD	1 hits
92	SERPINE1	1 hits
93	SIRT1	1 hits
94	SIRT3	1 hits
95	SLC16A3	1 hits
96	SLC2A1	1 hits
97	SLC2A4	1 hits
98	SRC	1 hits
99	STAT3	1 hits
100	STIM1	1 hits
101	STK11	1 hits
102	TBC1D1	1 hits
103	TBC1D4	1 hits
104	TFAP2A	1 hits
105	TJP1	1 hits
106	TP53	1 hits
107	TSC1	1 hits
108	TSC2	1 hits
109	TXNIP	1 hits
110	UCP1	1 hits
111	USF1	1 hits

Related Sentences

#	PMID	Sentence
1	2982681	When glycosylation in hemolysates of 11 type I diabetic subjects was compared with that from 7 normal subjects, significant increases were found in glycosylation of hemoglobin (Hb) (12.1 +/- 6.0% versus 4.7 +/- 0.5%) and purine nucleoside phosphorylase (PNP) (5.3 +/- 3.0% versus 2.1 +/- 0.5%).
2	2982681	However, no differences were found for nucleoside diphosphokinase (NDPK) (1.5 +/- 1.1% versus 1.0 +/- 0.4%) and adenylate kinase (AMPK) (0.5 +/- 0.4% versus 0.7 +/- 0.2%).
3	2982681	After 18 h, the percentages of glycosylation of Hb, PNP, NDPK, and AMPK were increased from normal values to 31, 24, 11, and 3, respectively.
4	2982681	When glycosylation in hemolysates of 11 type I diabetic subjects was compared with that from 7 normal subjects, significant increases were found in glycosylation of hemoglobin (Hb) (12.1 +/- 6.0% versus 4.7 +/- 0.5%) and purine nucleoside phosphorylase (PNP) (5.3 +/- 3.0% versus 2.1 +/- 0.5%).
5	2982681	However, no differences were found for nucleoside diphosphokinase (NDPK) (1.5 +/- 1.1% versus 1.0 +/- 0.4%) and adenylate kinase (AMPK) (0.5 +/- 0.4% versus 0.7 +/- 0.2%).
6	2982681	After 18 h, the percentages of glycosylation of Hb, PNP, NDPK, and AMPK were increased from normal values to 31, 24, 11, and 3, respectively.
7	10818001	Here, it is shown that the mutation is a nonconservative substitution (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK).
8	11547215	Other interesting therapeutic perspectives to treat insulin resistance lie in the development of inhibitors of protein tyrosine phosphatases and in the promotion of non insulin-dependent contraction-like muscle glucose uptake via stimulation of AMP protein kinase (AMPK).
9	11900364	This includes alterations in AMPK, ACC, and MCD activity in the diabetic rat heart.
10	12769732	The insulin-sensitizing role of the fat derived hormone adiponectin.
11	12769732	Adiponectin is an insulin-sensitizing hormone whose blood concentration is reduced in obesity and type 2 diabetes.
12	12769732	Administration of recombinant adiponectin in rodents increases glucose uptake and increases fat oxidation in muscle, reduces fatty acid uptake and hepatic glucose production in liver, and improves whole body insulin resistance.
13	12769732	The exact receptor and signaling systems are unknown, however, recent studies suggest adiponectin activates AMPK, a putative master metabolic regulator.
14	12769732	Thus, excitement surrounds the potential for adiponectin, or a homologue of adiponectin, as pharamacotherapy agents for patients suffering from the metabolic syndrome and more particularly for individuals with insulin resistance and type 2 diabetes.
15	14501164	[The mechanisms by which PPARgamma and adiponectin regulate glucose and lipid metabolism].
16	14501164	Heterozygous PPARgamma knockout mice and KKA(y) mice administered with a PPARgamma antagonist were protected from high-fat diet-induced adipocyte hypertrophy and insulin resistance.
17	14501164	Moderate reduction of PPARgamma activity prevented adipocyte hypertrophy, thereby diminution of TNFalpha, resistin, and FFA and upregulation of adiponectin and leptin.
18	14501164	Insulin resistance in the lipoatrophic mice and KKA(y) mice were ameliorated by replenishment of adiponectin.
19	14501164	Moreover, adiponectin transgenic mice ameliorated insulin resistance and diabetes, but not the obesity of ob/ob mice.
20	14501164	Furthermore, targeted disruption of the adiponectin gene caused moderate insulin resistance and glucose intolerance.
21	14501164	In muscle, adiponectin activated AMP kinase and PPARgamma pathways, thereby increasing beta-oxidation of lipids, leading to decreased TG content, which ameliorated muscle insulin resistance.
22	14501164	In the liver, adiponectin also activated AMPK, thereby downregulating PEPCK and G6Pase, leading to decreased glucose output from the liver.
23	14501164	In conclusion, PPARgamma plays a central role in the regulation of adipocyte hypertrophy and insulin sensitivity.
24	14501164	The upregulation of the adiponectin pathway by PPARgamma may play a role in the increased insulin sensitivity of heterozygous PPARgamma knockout mice, and activation of adiponectin pathway may provide novel therapeutic strategies for obesity-linked disorders such as type 2 diabetes and metabolic syndrome.
25	15235326	These DNA elements have been shown to bind the transcription factors myocyte enhancer factor 2 (MEF2) and GLUT4 enhancer factor (GEF).
26	15235326	Signals that link muscle contraction to the activation of transcription factors (MEF2, GEF) involved in increased expression of GLUT4 during exercise is another area needing further research.
27	15235326	Two signals that show promise are changes in the energy charge (acting through AMP activated kinase [AMPK]) and changes in intracellular calcium (acting through calcineurin [a calcium-calmodulin activated phosphatase] and calcium-calmodulin activated kinase [CAMK]).
28	15235326	There is good evidence that both increased AMPK activity and increased CAMK activity cause increased transcription of the GLUT4 gene.
29	15235326	These DNA elements have been shown to bind the transcription factors myocyte enhancer factor 2 (MEF2) and GLUT4 enhancer factor (GEF).
30	15235326	Signals that link muscle contraction to the activation of transcription factors (MEF2, GEF) involved in increased expression of GLUT4 during exercise is another area needing further research.
31	15235326	Two signals that show promise are changes in the energy charge (acting through AMP activated kinase [AMPK]) and changes in intracellular calcium (acting through calcineurin [a calcium-calmodulin activated phosphatase] and calcium-calmodulin activated kinase [CAMK]).
32	15235326	There is good evidence that both increased AMPK activity and increased CAMK activity cause increased transcription of the GLUT4 gene.
33	15235328	Insulin receptor substrate (IRS-1) phosphorylation, phosphatidylinositol (PI) 3-kinase activity, and glucose transport activity are impaired as a consequence of functional defects, whereas insulin receptor tyrosine phosphorylation, mitogen-activated protein kinase (MAPK) phosphorylation, and glycogen synthase activity are normal.
34	15235328	Using biotinylated photoaffinity labeling, we have shown that reduced cell surface GLUT4 levels can explain glucose transport defects in skeletal muscle from Type 2 diabetic patients under insulin-stimulated conditions.
35	15235328	We have recently determined the independent effects of insulin and hypoxia/AICAR exposure on glucose transport and cell surface GLUT4 content in skeletal muscle from nondiabetic and Type 2 diabetic subjects.
36	15235328	Hypoxia and AICAR increase glucose transport via an insulin-independent mechanism involving activation of 5'-AMP-activated kinase (AMPK).
37	15235328	AMPK signaling is intact, because 5-aminoimidazole-4-carboxamide 1-beta-D-ribonucleoside (AICAR) increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation to a similar extent in Type 2 diabetic and nondiabetic subjects.
38	15235328	Our studies highlight important AMPK-dependent and independent pathways in the regulation of GLUT4 and glucose transport activity in insulin resistant skeletal muscle.
39	15235328	Insulin receptor substrate (IRS-1) phosphorylation, phosphatidylinositol (PI) 3-kinase activity, and glucose transport activity are impaired as a consequence of functional defects, whereas insulin receptor tyrosine phosphorylation, mitogen-activated protein kinase (MAPK) phosphorylation, and glycogen synthase activity are normal.
40	15235328	Using biotinylated photoaffinity labeling, we have shown that reduced cell surface GLUT4 levels can explain glucose transport defects in skeletal muscle from Type 2 diabetic patients under insulin-stimulated conditions.
41	15235328	We have recently determined the independent effects of insulin and hypoxia/AICAR exposure on glucose transport and cell surface GLUT4 content in skeletal muscle from nondiabetic and Type 2 diabetic subjects.
42	15235328	Hypoxia and AICAR increase glucose transport via an insulin-independent mechanism involving activation of 5'-AMP-activated kinase (AMPK).
43	15235328	AMPK signaling is intact, because 5-aminoimidazole-4-carboxamide 1-beta-D-ribonucleoside (AICAR) increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation to a similar extent in Type 2 diabetic and nondiabetic subjects.
44	15235328	Our studies highlight important AMPK-dependent and independent pathways in the regulation of GLUT4 and glucose transport activity in insulin resistant skeletal muscle.
45	15235328	Insulin receptor substrate (IRS-1) phosphorylation, phosphatidylinositol (PI) 3-kinase activity, and glucose transport activity are impaired as a consequence of functional defects, whereas insulin receptor tyrosine phosphorylation, mitogen-activated protein kinase (MAPK) phosphorylation, and glycogen synthase activity are normal.
46	15235328	Using biotinylated photoaffinity labeling, we have shown that reduced cell surface GLUT4 levels can explain glucose transport defects in skeletal muscle from Type 2 diabetic patients under insulin-stimulated conditions.
47	15235328	We have recently determined the independent effects of insulin and hypoxia/AICAR exposure on glucose transport and cell surface GLUT4 content in skeletal muscle from nondiabetic and Type 2 diabetic subjects.
48	15235328	Hypoxia and AICAR increase glucose transport via an insulin-independent mechanism involving activation of 5'-AMP-activated kinase (AMPK).
49	15235328	AMPK signaling is intact, because 5-aminoimidazole-4-carboxamide 1-beta-D-ribonucleoside (AICAR) increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation to a similar extent in Type 2 diabetic and nondiabetic subjects.
50	15235328	Our studies highlight important AMPK-dependent and independent pathways in the regulation of GLUT4 and glucose transport activity in insulin resistant skeletal muscle.
51	15367397	Expression of protein phosphatase 2C (PP2C), which inactivates AMPK activity by dephosphorylation, was increased in untreated ZDF fa/fa rat hearts, but fell with TGZ treatment, suggesting that PP2C can influence AMPK activity.
52	15383372	Bombesin and nutrients independently and additively regulate hormone release from GIP/Ins cells.
53	15383372	Glucose-dependent insulinotropic polypeptide (GIP) regulates glucose homeostasis and high-fat diet-induced obesity and insulin resistance.
54	15383372	Bombesin-like peptides produced by enteric neurons and luminal nutrients stimulate GIP release in vivo.
55	15383372	We previously showed that PMA, bombesin, meat hydrolysate, glyceraldehyde, and methylpyruvate increase hormone release from a GIP-producing EE cell line (GIP/Ins cells).
56	15383372	Here we demonstrate that bombesin and nutrients additively stimulate hormone release from GIP/Ins cells.
57	15383372	In various cell systems, bombesin and PMA regulate cell physiology by activating PKD signaling in a PKC-dependent fashion, whereas nutrients regulate cell physiology by inhibiting AMPK signaling.
58	15383372	Western blot analyses of GIP/Ins cells using antibodies specific for activated and/or phosphorylated forms of PKD and AMPK and one substrate for each kinase revealed that bombesin and PMA, but not nutrients, activated PKC, but not PKD.
59	15383372	Conversely, nutrients, but not bombesin or PMA, inhibited AMPK activity.
60	15383372	Pharmacological studies showed that PKC inhibition blocked bombesin- and PMA-stimulated hormone release, but AMPK activation failed to suppress nutrient-stimulated hormone secretion.
61	15383372	Forced expression of constitutively active vs. dominant negative PKDs or AMPKs failed to perturb bombesin- or nutrient-stimulated hormone release.
62	15383372	Thus, in GIP/Ins cells, PKC regulates bombesin-stimulated hormone release, whereas nutrients may control hormone release by regulating the activity of AMPK-related kinases, rather than AMPK itself.
63	15383372	Bombesin and nutrients independently and additively regulate hormone release from GIP/Ins cells.
64	15383372	Glucose-dependent insulinotropic polypeptide (GIP) regulates glucose homeostasis and high-fat diet-induced obesity and insulin resistance.
65	15383372	Bombesin-like peptides produced by enteric neurons and luminal nutrients stimulate GIP release in vivo.
66	15383372	We previously showed that PMA, bombesin, meat hydrolysate, glyceraldehyde, and methylpyruvate increase hormone release from a GIP-producing EE cell line (GIP/Ins cells).
67	15383372	Here we demonstrate that bombesin and nutrients additively stimulate hormone release from GIP/Ins cells.
68	15383372	In various cell systems, bombesin and PMA regulate cell physiology by activating PKD signaling in a PKC-dependent fashion, whereas nutrients regulate cell physiology by inhibiting AMPK signaling.
69	15383372	Western blot analyses of GIP/Ins cells using antibodies specific for activated and/or phosphorylated forms of PKD and AMPK and one substrate for each kinase revealed that bombesin and PMA, but not nutrients, activated PKC, but not PKD.
70	15383372	Conversely, nutrients, but not bombesin or PMA, inhibited AMPK activity.
71	15383372	Pharmacological studies showed that PKC inhibition blocked bombesin- and PMA-stimulated hormone release, but AMPK activation failed to suppress nutrient-stimulated hormone secretion.
72	15383372	Forced expression of constitutively active vs. dominant negative PKDs or AMPKs failed to perturb bombesin- or nutrient-stimulated hormone release.
73	15383372	Thus, in GIP/Ins cells, PKC regulates bombesin-stimulated hormone release, whereas nutrients may control hormone release by regulating the activity of AMPK-related kinases, rather than AMPK itself.
74	15383372	Bombesin and nutrients independently and additively regulate hormone release from GIP/Ins cells.
75	15383372	Glucose-dependent insulinotropic polypeptide (GIP) regulates glucose homeostasis and high-fat diet-induced obesity and insulin resistance.
76	15383372	Bombesin-like peptides produced by enteric neurons and luminal nutrients stimulate GIP release in vivo.
77	15383372	We previously showed that PMA, bombesin, meat hydrolysate, glyceraldehyde, and methylpyruvate increase hormone release from a GIP-producing EE cell line (GIP/Ins cells).
78	15383372	Here we demonstrate that bombesin and nutrients additively stimulate hormone release from GIP/Ins cells.
79	15383372	In various cell systems, bombesin and PMA regulate cell physiology by activating PKD signaling in a PKC-dependent fashion, whereas nutrients regulate cell physiology by inhibiting AMPK signaling.
80	15383372	Western blot analyses of GIP/Ins cells using antibodies specific for activated and/or phosphorylated forms of PKD and AMPK and one substrate for each kinase revealed that bombesin and PMA, but not nutrients, activated PKC, but not PKD.
81	15383372	Conversely, nutrients, but not bombesin or PMA, inhibited AMPK activity.
82	15383372	Pharmacological studies showed that PKC inhibition blocked bombesin- and PMA-stimulated hormone release, but AMPK activation failed to suppress nutrient-stimulated hormone secretion.
83	15383372	Forced expression of constitutively active vs. dominant negative PKDs or AMPKs failed to perturb bombesin- or nutrient-stimulated hormone release.
84	15383372	Thus, in GIP/Ins cells, PKC regulates bombesin-stimulated hormone release, whereas nutrients may control hormone release by regulating the activity of AMPK-related kinases, rather than AMPK itself.
85	15383372	Bombesin and nutrients independently and additively regulate hormone release from GIP/Ins cells.
86	15383372	Glucose-dependent insulinotropic polypeptide (GIP) regulates glucose homeostasis and high-fat diet-induced obesity and insulin resistance.
87	15383372	Bombesin-like peptides produced by enteric neurons and luminal nutrients stimulate GIP release in vivo.
88	15383372	We previously showed that PMA, bombesin, meat hydrolysate, glyceraldehyde, and methylpyruvate increase hormone release from a GIP-producing EE cell line (GIP/Ins cells).
89	15383372	Here we demonstrate that bombesin and nutrients additively stimulate hormone release from GIP/Ins cells.
90	15383372	In various cell systems, bombesin and PMA regulate cell physiology by activating PKD signaling in a PKC-dependent fashion, whereas nutrients regulate cell physiology by inhibiting AMPK signaling.
91	15383372	Western blot analyses of GIP/Ins cells using antibodies specific for activated and/or phosphorylated forms of PKD and AMPK and one substrate for each kinase revealed that bombesin and PMA, but not nutrients, activated PKC, but not PKD.
92	15383372	Conversely, nutrients, but not bombesin or PMA, inhibited AMPK activity.
93	15383372	Pharmacological studies showed that PKC inhibition blocked bombesin- and PMA-stimulated hormone release, but AMPK activation failed to suppress nutrient-stimulated hormone secretion.
94	15383372	Forced expression of constitutively active vs. dominant negative PKDs or AMPKs failed to perturb bombesin- or nutrient-stimulated hormone release.
95	15383372	Thus, in GIP/Ins cells, PKC regulates bombesin-stimulated hormone release, whereas nutrients may control hormone release by regulating the activity of AMPK-related kinases, rather than AMPK itself.
96	15383372	Bombesin and nutrients independently and additively regulate hormone release from GIP/Ins cells.
97	15383372	Glucose-dependent insulinotropic polypeptide (GIP) regulates glucose homeostasis and high-fat diet-induced obesity and insulin resistance.
98	15383372	Bombesin-like peptides produced by enteric neurons and luminal nutrients stimulate GIP release in vivo.
99	15383372	We previously showed that PMA, bombesin, meat hydrolysate, glyceraldehyde, and methylpyruvate increase hormone release from a GIP-producing EE cell line (GIP/Ins cells).
100	15383372	Here we demonstrate that bombesin and nutrients additively stimulate hormone release from GIP/Ins cells.
101	15383372	In various cell systems, bombesin and PMA regulate cell physiology by activating PKD signaling in a PKC-dependent fashion, whereas nutrients regulate cell physiology by inhibiting AMPK signaling.
102	15383372	Western blot analyses of GIP/Ins cells using antibodies specific for activated and/or phosphorylated forms of PKD and AMPK and one substrate for each kinase revealed that bombesin and PMA, but not nutrients, activated PKC, but not PKD.
103	15383372	Conversely, nutrients, but not bombesin or PMA, inhibited AMPK activity.
104	15383372	Pharmacological studies showed that PKC inhibition blocked bombesin- and PMA-stimulated hormone release, but AMPK activation failed to suppress nutrient-stimulated hormone secretion.
105	15383372	Forced expression of constitutively active vs. dominant negative PKDs or AMPKs failed to perturb bombesin- or nutrient-stimulated hormone release.
106	15383372	Thus, in GIP/Ins cells, PKC regulates bombesin-stimulated hormone release, whereas nutrients may control hormone release by regulating the activity of AMPK-related kinases, rather than AMPK itself.
107	15383372	Bombesin and nutrients independently and additively regulate hormone release from GIP/Ins cells.
108	15383372	Glucose-dependent insulinotropic polypeptide (GIP) regulates glucose homeostasis and high-fat diet-induced obesity and insulin resistance.
109	15383372	Bombesin-like peptides produced by enteric neurons and luminal nutrients stimulate GIP release in vivo.
110	15383372	We previously showed that PMA, bombesin, meat hydrolysate, glyceraldehyde, and methylpyruvate increase hormone release from a GIP-producing EE cell line (GIP/Ins cells).
111	15383372	Here we demonstrate that bombesin and nutrients additively stimulate hormone release from GIP/Ins cells.
112	15383372	In various cell systems, bombesin and PMA regulate cell physiology by activating PKD signaling in a PKC-dependent fashion, whereas nutrients regulate cell physiology by inhibiting AMPK signaling.
113	15383372	Western blot analyses of GIP/Ins cells using antibodies specific for activated and/or phosphorylated forms of PKD and AMPK and one substrate for each kinase revealed that bombesin and PMA, but not nutrients, activated PKC, but not PKD.
114	15383372	Conversely, nutrients, but not bombesin or PMA, inhibited AMPK activity.
115	15383372	Pharmacological studies showed that PKC inhibition blocked bombesin- and PMA-stimulated hormone release, but AMPK activation failed to suppress nutrient-stimulated hormone secretion.
116	15383372	Forced expression of constitutively active vs. dominant negative PKDs or AMPKs failed to perturb bombesin- or nutrient-stimulated hormone release.
117	15383372	Thus, in GIP/Ins cells, PKC regulates bombesin-stimulated hormone release, whereas nutrients may control hormone release by regulating the activity of AMPK-related kinases, rather than AMPK itself.
118	15589686	Among those, adiponectin is an insulin-sensitizing and anti-inflammatory adipokine, concentrations of which are decreased in obesity-associated metabolic and vascular disorders.
119	15589686	Recently, two adiponectin receptors (AdipoR) have been isolated and adenosine monophosphate kinase (AMPK), as well as acetyl coenzyme A carboxylase (ACC), appear to be critical downstream mediators for various effects of this adipokine.
120	15589686	Of clinical interest, thiazolidinediones (TZDs) which are used in the treatment of type 2 diabetes stimulate adiponectin expression and secretion whereas several hormones dysregulated in insulin resistance and obesity downregulate this adipokine.
121	15589686	The current knowledge on regulation and function of adiponectin in obesity, insulin resistance, and cardiovascular disease is summarized in this review and its clinical implications are discussed.
122	15732245	Pharmacological substances, which stimulate AMPK-activity ameliorate insulin resistance induced by free fatty acids.
123	15732245	Various therapeutical interventions for the improvement of insulin sensitivity, including weight loss, physical exercise, as well as metformin and glitazones, increase AMPK activity.
124	15732245	Pharmacological substances, which stimulate AMPK-activity ameliorate insulin resistance induced by free fatty acids.
125	15732245	Various therapeutical interventions for the improvement of insulin sensitivity, including weight loss, physical exercise, as well as metformin and glitazones, increase AMPK activity.
126	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
127	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
128	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
129	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
130	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
131	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
132	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
133	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
134	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
135	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
136	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
137	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
138	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
139	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
140	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
141	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
142	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
143	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
144	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
145	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
146	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
147	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
148	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
149	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
150	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
151	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
152	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
153	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
154	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
155	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
156	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
157	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
158	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
159	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
160	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
161	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
162	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
163	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
164	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
165	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
166	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
167	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
168	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
169	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
170	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
171	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
172	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
173	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
174	15769985	In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2.
175	15769985	In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects.
176	15769985	Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052).
177	15769985	In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside.
178	15769985	In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation.
179	15769985	In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected.
180	15769985	Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1.
181	15769985	These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
182	15823720	AMPK activation as a strategy for reversing the endothelial lipotoxicity underlying the increased vascular risk associated with insulin resistance syndrome.
183	15823720	The endotheliopathy associated with insulin resistance syndrome appears to result largely from excessive free fatty acid (FFA) exposure that boosts endothelial production of diacylglycerol, thereby activating protein kinase C.
184	15823720	In addition, pharmacological activation of endothelial AMP-activated kinase (AMPK), as with the drug metformin, has the potential to decrease the FFA content of endothelial cells by stimulating fat oxidation; AMPK may also suppress endothelial de novo synthesis of diacylglycerol by inhibiting glycerol-3-phosphate acyltransferase.
185	15823720	More generally, metformin - or, preferably, better tolerated activators of AMPK - may have considerable potential for promoting vascular health in the large proportion of the adult population afflicted with insulin resistance syndrome.
186	15823720	AMPK activation as a strategy for reversing the endothelial lipotoxicity underlying the increased vascular risk associated with insulin resistance syndrome.
187	15823720	The endotheliopathy associated with insulin resistance syndrome appears to result largely from excessive free fatty acid (FFA) exposure that boosts endothelial production of diacylglycerol, thereby activating protein kinase C.
188	15823720	In addition, pharmacological activation of endothelial AMP-activated kinase (AMPK), as with the drug metformin, has the potential to decrease the FFA content of endothelial cells by stimulating fat oxidation; AMPK may also suppress endothelial de novo synthesis of diacylglycerol by inhibiting glycerol-3-phosphate acyltransferase.
189	15823720	More generally, metformin - or, preferably, better tolerated activators of AMPK - may have considerable potential for promoting vascular health in the large proportion of the adult population afflicted with insulin resistance syndrome.
190	15823720	AMPK activation as a strategy for reversing the endothelial lipotoxicity underlying the increased vascular risk associated with insulin resistance syndrome.
191	15823720	The endotheliopathy associated with insulin resistance syndrome appears to result largely from excessive free fatty acid (FFA) exposure that boosts endothelial production of diacylglycerol, thereby activating protein kinase C.
192	15823720	In addition, pharmacological activation of endothelial AMP-activated kinase (AMPK), as with the drug metformin, has the potential to decrease the FFA content of endothelial cells by stimulating fat oxidation; AMPK may also suppress endothelial de novo synthesis of diacylglycerol by inhibiting glycerol-3-phosphate acyltransferase.
193	15823720	More generally, metformin - or, preferably, better tolerated activators of AMPK - may have considerable potential for promoting vascular health in the large proportion of the adult population afflicted with insulin resistance syndrome.
194	16054052	These mice have altered cellular and systemic lipid transport and composition, leading to enhanced insulin receptor signaling, enhanced muscle AMP-activated kinase (AMP-K) activity, and dramatically reduced liver stearoyl-CoA desaturase-1 (SCD-1) activity underlying their phenotype.
195	16148943	The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism.
196	16148943	Here we show that hormonal and energy-sensing pathways converge on the coactivator TORC2 (transducer of regulated CREB activity 2) to modulate glucose output.
197	16148943	Sequestered in the cytoplasm under feeding conditions, TORC2 is dephosphorylated and transported to the nucleus where it enhances CREB-dependent transcription in response to fasting stimuli.
198	16148943	Conversely, signals that activate AMPK attenuate the gluconeogenic programme by promoting TORC2 phosphorylation and blocking its nuclear accumulation.
199	16352671	In this study, we examined whether insulin-resistant obese Zucker rats have abnormalities in the AMPK pathway.
200	16352671	We compared AMPK and ACC phosphorylation and the protein content of the upstream AMPK kinase LKB1 and the AMPK-regulated transcriptional coactivator PPARgamma coactivator-1 (PGC-1) in gastrocnemius of sedentary obese Zucker rats and sedentary lean Zucker rats.
201	16352671	Protein expression of the AMPK kinase LKB1 was also reduced in the muscle from obese rats by 43%.
202	16352671	In obese rats, phosphorylation of ACC and protein expression of PGC-1alpha, two AMPK-regulated proteins, tended to be reduced by 50 (P = 0.07) and 35% (P = 0.1), respectively.
203	16352671	Furthermore, training also significantly increased LKB1 and PGC-1alpha protein content 2.8- and 2.5-fold, respectively, in the obese rats.
204	16352671	LKB1 protein strongly correlated with hexokinase II activity (r = 0.75, P = 0.001), citrate synthase activity (r = 0.54, P = 0.02), and PGC-1alpha protein content (r = 0.81, P < 0.001).
205	16352671	In summary, obese insulin-resistant rodents have abnormalities in the LKB1-AMPK-PGC-1 pathway in muscle, and these abnormalities can be restored by training.
206	16352671	In this study, we examined whether insulin-resistant obese Zucker rats have abnormalities in the AMPK pathway.
207	16352671	We compared AMPK and ACC phosphorylation and the protein content of the upstream AMPK kinase LKB1 and the AMPK-regulated transcriptional coactivator PPARgamma coactivator-1 (PGC-1) in gastrocnemius of sedentary obese Zucker rats and sedentary lean Zucker rats.
208	16352671	Protein expression of the AMPK kinase LKB1 was also reduced in the muscle from obese rats by 43%.
209	16352671	In obese rats, phosphorylation of ACC and protein expression of PGC-1alpha, two AMPK-regulated proteins, tended to be reduced by 50 (P = 0.07) and 35% (P = 0.1), respectively.
210	16352671	Furthermore, training also significantly increased LKB1 and PGC-1alpha protein content 2.8- and 2.5-fold, respectively, in the obese rats.
211	16352671	LKB1 protein strongly correlated with hexokinase II activity (r = 0.75, P = 0.001), citrate synthase activity (r = 0.54, P = 0.02), and PGC-1alpha protein content (r = 0.81, P < 0.001).
212	16352671	In summary, obese insulin-resistant rodents have abnormalities in the LKB1-AMPK-PGC-1 pathway in muscle, and these abnormalities can be restored by training.
213	16352671	In this study, we examined whether insulin-resistant obese Zucker rats have abnormalities in the AMPK pathway.
214	16352671	We compared AMPK and ACC phosphorylation and the protein content of the upstream AMPK kinase LKB1 and the AMPK-regulated transcriptional coactivator PPARgamma coactivator-1 (PGC-1) in gastrocnemius of sedentary obese Zucker rats and sedentary lean Zucker rats.
215	16352671	Protein expression of the AMPK kinase LKB1 was also reduced in the muscle from obese rats by 43%.
216	16352671	In obese rats, phosphorylation of ACC and protein expression of PGC-1alpha, two AMPK-regulated proteins, tended to be reduced by 50 (P = 0.07) and 35% (P = 0.1), respectively.
217	16352671	Furthermore, training also significantly increased LKB1 and PGC-1alpha protein content 2.8- and 2.5-fold, respectively, in the obese rats.
218	16352671	LKB1 protein strongly correlated with hexokinase II activity (r = 0.75, P = 0.001), citrate synthase activity (r = 0.54, P = 0.02), and PGC-1alpha protein content (r = 0.81, P < 0.001).
219	16352671	In summary, obese insulin-resistant rodents have abnormalities in the LKB1-AMPK-PGC-1 pathway in muscle, and these abnormalities can be restored by training.
220	16352671	In this study, we examined whether insulin-resistant obese Zucker rats have abnormalities in the AMPK pathway.
221	16352671	We compared AMPK and ACC phosphorylation and the protein content of the upstream AMPK kinase LKB1 and the AMPK-regulated transcriptional coactivator PPARgamma coactivator-1 (PGC-1) in gastrocnemius of sedentary obese Zucker rats and sedentary lean Zucker rats.
222	16352671	Protein expression of the AMPK kinase LKB1 was also reduced in the muscle from obese rats by 43%.
223	16352671	In obese rats, phosphorylation of ACC and protein expression of PGC-1alpha, two AMPK-regulated proteins, tended to be reduced by 50 (P = 0.07) and 35% (P = 0.1), respectively.
224	16352671	Furthermore, training also significantly increased LKB1 and PGC-1alpha protein content 2.8- and 2.5-fold, respectively, in the obese rats.
225	16352671	LKB1 protein strongly correlated with hexokinase II activity (r = 0.75, P = 0.001), citrate synthase activity (r = 0.54, P = 0.02), and PGC-1alpha protein content (r = 0.81, P < 0.001).
226	16352671	In summary, obese insulin-resistant rodents have abnormalities in the LKB1-AMPK-PGC-1 pathway in muscle, and these abnormalities can be restored by training.
227	16354680	Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation.
228	16354680	Here, we demonstrate that nutrients suppress phosphatidylinositol 3 (PI3)-kinase/Akt signaling via Raptor-dependent mTOR (mammalian target of rapamycin)-mediated phosphorylation of insulin receptor substrate 1 (IRS-1).
229	16354680	These serines lie close to the Y(632)MPM motif that is implicated in the binding of p85alpha/p110alpha PI3-kinase to IRS-1 upon insulin stimulation.
230	16354680	Phosphomimicking mutations of these serines block insulin-stimulated activation of IRS-1-associated PI3-kinase.
231	16354680	Knockdown of Raptor as well as activators of the LKB1/AMPK pathway, such as the widely used antidiabetic compound metformin, suppress IRS-1 Ser636/639 phosphorylation and reverse mTOR-mediated inhibition on PI3-kinase/Akt signaling.
232	16354680	Thus, diabetes-related hyperglycemia hyperactivates the mTOR pathway and may lead to insulin resistance due to suppression of IRS-1-dependent PI3-kinase/Akt signaling.
233	16503364	Similarly, the treatment of primary cultured rat hepatocytes with dexamethasone (1microM) increased expression of the AMPKalpha1 subunit, AICAR-induced AMPK phosphorylation and kinase activity.
234	16505254	Haplotype structures and large-scale association testing of the 5' AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB2 [corrected] with type 2 diabetes.
235	16505254	Of the seven genes that encode AMPK isoforms, we initially chose PRKAA2, PRKAB1, and PRKAB2 because of their higher prior probability of association with type 2 diabetes, based on previous reports of genetic linkage, functional molecular studies, expression patterns, and pharmacological evidence.
236	16505254	Several nominal associations of variants in PRKAA2 and PRKAB1 with BMI appear to be consistent with statistical noise.
237	16505254	Haplotype structures and large-scale association testing of the 5' AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB2 [corrected] with type 2 diabetes.
238	16505254	Of the seven genes that encode AMPK isoforms, we initially chose PRKAA2, PRKAB1, and PRKAB2 because of their higher prior probability of association with type 2 diabetes, based on previous reports of genetic linkage, functional molecular studies, expression patterns, and pharmacological evidence.
239	16505254	Several nominal associations of variants in PRKAA2 and PRKAB1 with BMI appear to be consistent with statistical noise.
240	16505254	Haplotype structures and large-scale association testing of the 5' AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB2 [corrected] with type 2 diabetes.
241	16505254	Of the seven genes that encode AMPK isoforms, we initially chose PRKAA2, PRKAB1, and PRKAB2 because of their higher prior probability of association with type 2 diabetes, based on previous reports of genetic linkage, functional molecular studies, expression patterns, and pharmacological evidence.
242	16505254	Several nominal associations of variants in PRKAA2 and PRKAB1 with BMI appear to be consistent with statistical noise.
243	16563350	Cytokine secretion by human adipocytes is differentially regulated by adiponectin, AICAR, and troglitazone.
244	16563350	Secretion of IL-6, IL-8, MIP-1alpha/beta, and MCP-1 by adipocytes was found to be downregulated by adiponectin.
245	16563350	In parallel to adiponectin, the AMPK activator AICAR also decreased the secretion of most of the measured cytokines including IL-6 and MIP-1alpha/beta but not IL-8.
246	16567511	The gene encoding the alpha2 isoform of the catalytic subunit of AMPK (PRKAA2) is located at one of the Japanese type 2 diabetes loci mapped by our previous genome scan (1p36-32).
247	16567511	PRKAA2 is, therefore, a good candidate gene for insulin resistance and type 2 diabetes.
248	16567511	We speculate that the PRKAA2 gene influences insulin resistance and susceptibility to type 2 diabetes in the Japanese population.
249	16567511	The gene encoding the alpha2 isoform of the catalytic subunit of AMPK (PRKAA2) is located at one of the Japanese type 2 diabetes loci mapped by our previous genome scan (1p36-32).
250	16567511	PRKAA2 is, therefore, a good candidate gene for insulin resistance and type 2 diabetes.
251	16567511	We speculate that the PRKAA2 gene influences insulin resistance and susceptibility to type 2 diabetes in the Japanese population.
252	16567511	The gene encoding the alpha2 isoform of the catalytic subunit of AMPK (PRKAA2) is located at one of the Japanese type 2 diabetes loci mapped by our previous genome scan (1p36-32).
253	16567511	PRKAA2 is, therefore, a good candidate gene for insulin resistance and type 2 diabetes.
254	16567511	We speculate that the PRKAA2 gene influences insulin resistance and susceptibility to type 2 diabetes in the Japanese population.
255	16620308	Glucose transporter isoform 4 gene expression is increased immediately following a single bout of exercise, and the GLUT-4 enhancer factor (GEF) and myocyte enhancer factor 2 (MEF2) transcription factors are required for this response.
256	16620308	These studies find possible roles for histone deacetylase 5 (HDAC5), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) and p38 mitogen-activated protein kinase (MAPK) in regulating MEF2 through a series of complex interactions potentially involving MEF2 repression, coactivation and phosphorylation. 4.
257	16804058	Regulation of metabolic responses by adipocyte/macrophage Fatty Acid-binding proteins in leptin-deficient mice.
258	16804058	In animals lacking the adipocyte/macrophage FABP isoforms aP2 and mal1, there is strong protection against diet-induced obesity, insulin resistance, type 2 diabetes, fatty liver disease, and hypercholesterolemic atherosclerosis.
259	16804058	On high-fat diet, FABP-deficient mice also exhibit enhanced muscle AMP-activated kinase (AMPK) and reduced liver stearoyl-CoA desaturase-1 (SCD-1) activities.
260	16804058	These results indicated that both decreased body weight and enhanced muscle AMPK activity in aP2-mal1(-/-) mice are potentially leptin dependent but improved systemic insulin sensitivity and protection from liver fatty infiltration are largely unrelated to leptin action and that insulin-sensitizing effects of FABP deficiency are, at least in part, independent of its effects on total-body adiposity.
261	16804058	Regulation of metabolic responses by adipocyte/macrophage Fatty Acid-binding proteins in leptin-deficient mice.
262	16804058	In animals lacking the adipocyte/macrophage FABP isoforms aP2 and mal1, there is strong protection against diet-induced obesity, insulin resistance, type 2 diabetes, fatty liver disease, and hypercholesterolemic atherosclerosis.
263	16804058	On high-fat diet, FABP-deficient mice also exhibit enhanced muscle AMP-activated kinase (AMPK) and reduced liver stearoyl-CoA desaturase-1 (SCD-1) activities.
264	16804058	These results indicated that both decreased body weight and enhanced muscle AMPK activity in aP2-mal1(-/-) mice are potentially leptin dependent but improved systemic insulin sensitivity and protection from liver fatty infiltration are largely unrelated to leptin action and that insulin-sensitizing effects of FABP deficiency are, at least in part, independent of its effects on total-body adiposity.
265	16842543	Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells.
266	16842543	However, 3',5'-cyclic adenosine monophosphate-activated protein kinase (AMPK), another important glucose transport stimulatory mediator via an insulin-independent pathway, was not influenced by melatonin treatment.
267	16842543	Activity of p38 mitogen-activated protein kinase (MAPK), a downstream mediator of AMPK, was also not changed by melatonin.
268	16842543	Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells.
269	16842543	However, 3',5'-cyclic adenosine monophosphate-activated protein kinase (AMPK), another important glucose transport stimulatory mediator via an insulin-independent pathway, was not influenced by melatonin treatment.
270	16842543	Activity of p38 mitogen-activated protein kinase (MAPK), a downstream mediator of AMPK, was also not changed by melatonin.
271	16949049	Keratinocytes were incubated for 12 h with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
272	16949049	They also suggest that AMPK activators, such as AICAR and troglitazone, inhibit keratinocyte growth and that the inhibition of cell growth by 1,25-dihydroxyvitamin D3 is AMPK-independent.
273	16949049	Keratinocytes were incubated for 12 h with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
274	16949049	They also suggest that AMPK activators, such as AICAR and troglitazone, inhibit keratinocyte growth and that the inhibition of cell growth by 1,25-dihydroxyvitamin D3 is AMPK-independent.
275	17046229	Such proteins include AMPK, Rheb and the tumor suppressors LKB1, p53, and Tsc1/2.
276	17083919	LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
277	17083919	LKB1 is a 50 kDa serine/threonine kinase that phosphorylates and activates the catalytic subunit of AMPK at its T-loop residue Thr 172.
278	17083919	When analyzed by immunoblotting with the antibody against Thr172-phosphorylated AMPK, the phosphorylation of AMPK was increased (2.5-fold) and decreased (0.4-fold) in cells expressing CA and DN LKB1, respectively, as compared with Lac-Z expressing control cells.
279	17083919	Immunoprecipitation experiments, using isoform-specific antibody, revealed these alterations of AMPK phosphorylation to be attributable to altered phosphorylation of AMPK alpha2, but not alpha1 catalytic subunits, strongly suggesting the alpha2 catalytic subunit to be the major substrate for LKB1 in mammalian cells.
280	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
281	17083919	These results may explain the difference in AMPK activation mechanisms between AMP and phenformin, and also indicate that AMPK phosphorylation by LKB1 is involved in AMP-stimulated AMPK activation.
282	17083919	As a downstream target for AMPK, AICAR-induced glucose uptake and ACCbeta phosphorylation were found to be significantly reduced in DN LKB1 expressing C2C12 cells.
283	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
284	17083919	These results demonstrate that LKB1 is a crucial regulator of AMPK activation in muscle and liver cells and, therefore, that LKB1 activity is potentially of importance to our understanding of glucose and lipid metabolism.
285	17083919	LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
286	17083919	LKB1 is a 50 kDa serine/threonine kinase that phosphorylates and activates the catalytic subunit of AMPK at its T-loop residue Thr 172.
287	17083919	When analyzed by immunoblotting with the antibody against Thr172-phosphorylated AMPK, the phosphorylation of AMPK was increased (2.5-fold) and decreased (0.4-fold) in cells expressing CA and DN LKB1, respectively, as compared with Lac-Z expressing control cells.
288	17083919	Immunoprecipitation experiments, using isoform-specific antibody, revealed these alterations of AMPK phosphorylation to be attributable to altered phosphorylation of AMPK alpha2, but not alpha1 catalytic subunits, strongly suggesting the alpha2 catalytic subunit to be the major substrate for LKB1 in mammalian cells.
289	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
290	17083919	These results may explain the difference in AMPK activation mechanisms between AMP and phenformin, and also indicate that AMPK phosphorylation by LKB1 is involved in AMP-stimulated AMPK activation.
291	17083919	As a downstream target for AMPK, AICAR-induced glucose uptake and ACCbeta phosphorylation were found to be significantly reduced in DN LKB1 expressing C2C12 cells.
292	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
293	17083919	These results demonstrate that LKB1 is a crucial regulator of AMPK activation in muscle and liver cells and, therefore, that LKB1 activity is potentially of importance to our understanding of glucose and lipid metabolism.
294	17083919	LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
295	17083919	LKB1 is a 50 kDa serine/threonine kinase that phosphorylates and activates the catalytic subunit of AMPK at its T-loop residue Thr 172.
296	17083919	When analyzed by immunoblotting with the antibody against Thr172-phosphorylated AMPK, the phosphorylation of AMPK was increased (2.5-fold) and decreased (0.4-fold) in cells expressing CA and DN LKB1, respectively, as compared with Lac-Z expressing control cells.
297	17083919	Immunoprecipitation experiments, using isoform-specific antibody, revealed these alterations of AMPK phosphorylation to be attributable to altered phosphorylation of AMPK alpha2, but not alpha1 catalytic subunits, strongly suggesting the alpha2 catalytic subunit to be the major substrate for LKB1 in mammalian cells.
298	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
299	17083919	These results may explain the difference in AMPK activation mechanisms between AMP and phenformin, and also indicate that AMPK phosphorylation by LKB1 is involved in AMP-stimulated AMPK activation.
300	17083919	As a downstream target for AMPK, AICAR-induced glucose uptake and ACCbeta phosphorylation were found to be significantly reduced in DN LKB1 expressing C2C12 cells.
301	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
302	17083919	These results demonstrate that LKB1 is a crucial regulator of AMPK activation in muscle and liver cells and, therefore, that LKB1 activity is potentially of importance to our understanding of glucose and lipid metabolism.
303	17083919	LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
304	17083919	LKB1 is a 50 kDa serine/threonine kinase that phosphorylates and activates the catalytic subunit of AMPK at its T-loop residue Thr 172.
305	17083919	When analyzed by immunoblotting with the antibody against Thr172-phosphorylated AMPK, the phosphorylation of AMPK was increased (2.5-fold) and decreased (0.4-fold) in cells expressing CA and DN LKB1, respectively, as compared with Lac-Z expressing control cells.
306	17083919	Immunoprecipitation experiments, using isoform-specific antibody, revealed these alterations of AMPK phosphorylation to be attributable to altered phosphorylation of AMPK alpha2, but not alpha1 catalytic subunits, strongly suggesting the alpha2 catalytic subunit to be the major substrate for LKB1 in mammalian cells.
307	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
308	17083919	These results may explain the difference in AMPK activation mechanisms between AMP and phenformin, and also indicate that AMPK phosphorylation by LKB1 is involved in AMP-stimulated AMPK activation.
309	17083919	As a downstream target for AMPK, AICAR-induced glucose uptake and ACCbeta phosphorylation were found to be significantly reduced in DN LKB1 expressing C2C12 cells.
310	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
311	17083919	These results demonstrate that LKB1 is a crucial regulator of AMPK activation in muscle and liver cells and, therefore, that LKB1 activity is potentially of importance to our understanding of glucose and lipid metabolism.
312	17083919	LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
313	17083919	LKB1 is a 50 kDa serine/threonine kinase that phosphorylates and activates the catalytic subunit of AMPK at its T-loop residue Thr 172.
314	17083919	When analyzed by immunoblotting with the antibody against Thr172-phosphorylated AMPK, the phosphorylation of AMPK was increased (2.5-fold) and decreased (0.4-fold) in cells expressing CA and DN LKB1, respectively, as compared with Lac-Z expressing control cells.
315	17083919	Immunoprecipitation experiments, using isoform-specific antibody, revealed these alterations of AMPK phosphorylation to be attributable to altered phosphorylation of AMPK alpha2, but not alpha1 catalytic subunits, strongly suggesting the alpha2 catalytic subunit to be the major substrate for LKB1 in mammalian cells.
316	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
317	17083919	These results may explain the difference in AMPK activation mechanisms between AMP and phenformin, and also indicate that AMPK phosphorylation by LKB1 is involved in AMP-stimulated AMPK activation.
318	17083919	As a downstream target for AMPK, AICAR-induced glucose uptake and ACCbeta phosphorylation were found to be significantly reduced in DN LKB1 expressing C2C12 cells.
319	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
320	17083919	These results demonstrate that LKB1 is a crucial regulator of AMPK activation in muscle and liver cells and, therefore, that LKB1 activity is potentially of importance to our understanding of glucose and lipid metabolism.
321	17083919	LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
322	17083919	LKB1 is a 50 kDa serine/threonine kinase that phosphorylates and activates the catalytic subunit of AMPK at its T-loop residue Thr 172.
323	17083919	When analyzed by immunoblotting with the antibody against Thr172-phosphorylated AMPK, the phosphorylation of AMPK was increased (2.5-fold) and decreased (0.4-fold) in cells expressing CA and DN LKB1, respectively, as compared with Lac-Z expressing control cells.
324	17083919	Immunoprecipitation experiments, using isoform-specific antibody, revealed these alterations of AMPK phosphorylation to be attributable to altered phosphorylation of AMPK alpha2, but not alpha1 catalytic subunits, strongly suggesting the alpha2 catalytic subunit to be the major substrate for LKB1 in mammalian cells.
325	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
326	17083919	These results may explain the difference in AMPK activation mechanisms between AMP and phenformin, and also indicate that AMPK phosphorylation by LKB1 is involved in AMP-stimulated AMPK activation.
327	17083919	As a downstream target for AMPK, AICAR-induced glucose uptake and ACCbeta phosphorylation were found to be significantly reduced in DN LKB1 expressing C2C12 cells.
328	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
329	17083919	These results demonstrate that LKB1 is a crucial regulator of AMPK activation in muscle and liver cells and, therefore, that LKB1 activity is potentially of importance to our understanding of glucose and lipid metabolism.
330	17083919	LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
331	17083919	LKB1 is a 50 kDa serine/threonine kinase that phosphorylates and activates the catalytic subunit of AMPK at its T-loop residue Thr 172.
332	17083919	When analyzed by immunoblotting with the antibody against Thr172-phosphorylated AMPK, the phosphorylation of AMPK was increased (2.5-fold) and decreased (0.4-fold) in cells expressing CA and DN LKB1, respectively, as compared with Lac-Z expressing control cells.
333	17083919	Immunoprecipitation experiments, using isoform-specific antibody, revealed these alterations of AMPK phosphorylation to be attributable to altered phosphorylation of AMPK alpha2, but not alpha1 catalytic subunits, strongly suggesting the alpha2 catalytic subunit to be the major substrate for LKB1 in mammalian cells.
334	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
335	17083919	These results may explain the difference in AMPK activation mechanisms between AMP and phenformin, and also indicate that AMPK phosphorylation by LKB1 is involved in AMP-stimulated AMPK activation.
336	17083919	As a downstream target for AMPK, AICAR-induced glucose uptake and ACCbeta phosphorylation were found to be significantly reduced in DN LKB1 expressing C2C12 cells.
337	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
338	17083919	These results demonstrate that LKB1 is a crucial regulator of AMPK activation in muscle and liver cells and, therefore, that LKB1 activity is potentially of importance to our understanding of glucose and lipid metabolism.
339	17083919	LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
340	17083919	LKB1 is a 50 kDa serine/threonine kinase that phosphorylates and activates the catalytic subunit of AMPK at its T-loop residue Thr 172.
341	17083919	When analyzed by immunoblotting with the antibody against Thr172-phosphorylated AMPK, the phosphorylation of AMPK was increased (2.5-fold) and decreased (0.4-fold) in cells expressing CA and DN LKB1, respectively, as compared with Lac-Z expressing control cells.
342	17083919	Immunoprecipitation experiments, using isoform-specific antibody, revealed these alterations of AMPK phosphorylation to be attributable to altered phosphorylation of AMPK alpha2, but not alpha1 catalytic subunits, strongly suggesting the alpha2 catalytic subunit to be the major substrate for LKB1 in mammalian cells.
343	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
344	17083919	These results may explain the difference in AMPK activation mechanisms between AMP and phenformin, and also indicate that AMPK phosphorylation by LKB1 is involved in AMP-stimulated AMPK activation.
345	17083919	As a downstream target for AMPK, AICAR-induced glucose uptake and ACCbeta phosphorylation were found to be significantly reduced in DN LKB1 expressing C2C12 cells.
346	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
347	17083919	These results demonstrate that LKB1 is a crucial regulator of AMPK activation in muscle and liver cells and, therefore, that LKB1 activity is potentially of importance to our understanding of glucose and lipid metabolism.
348	17208384	Adipocyte-derived hormones, including adiponectin and leptin, regulate systemic insulin sensitivity in accordance to existing triglyceride reserves.
349	17208384	Leptin levels reflect existing fat mass and the adipokine negatively regulates insulin action in adipose tissue.
350	17208384	Adiponectin, on the other hand, preserves insulin sensitivity via transient increments of AMPK activity and its circulating levels seem to reflect the adipogenic capacity of adipose tissue.
351	17208384	Because adiponectin and insulin synergize in their postprandial actions, it seems evident that inadequate adiponectin production causes systemic insulin resistance.
352	17208384	As a consequence, compounds that either increase adiponectin production or mimic its actions can be considered as an efficient strategy for improving insulin sensitivity in type 2 diabetics.
353	17208384	Finally, after delineating critical nodes of insulin and adipokine crosstalk, putative pathways are proposed by which adiponectin and leptin cooperatively regulate systemic insulin sensitivity in accordance to existing fat mass.
354	17208384	By amplifying insulin action downstream of PI3K, leptin exerts negative feedback on insulin signaling via mTOR-dependent pathways that target IRS-1 for serine phosphorylation and protein degradation.
355	17208384	Adiponectin-mediated increments of AMPK activity, on the other hand, may attenuate mTOR signaling, leading to the preservation of insulin sensitivity in periods of increased nutrient availability.
356	17208384	Considering that leptin and adiponectin are inversely associated with BMI, the proposed model provides a plausible explanation for the observation that leptin exerts strong negative feedback on systemic insulin sensitivity, while increasing PIP3 availability.
357	17208384	Adipocyte-derived hormones, including adiponectin and leptin, regulate systemic insulin sensitivity in accordance to existing triglyceride reserves.
358	17208384	Leptin levels reflect existing fat mass and the adipokine negatively regulates insulin action in adipose tissue.
359	17208384	Adiponectin, on the other hand, preserves insulin sensitivity via transient increments of AMPK activity and its circulating levels seem to reflect the adipogenic capacity of adipose tissue.
360	17208384	Because adiponectin and insulin synergize in their postprandial actions, it seems evident that inadequate adiponectin production causes systemic insulin resistance.
361	17208384	As a consequence, compounds that either increase adiponectin production or mimic its actions can be considered as an efficient strategy for improving insulin sensitivity in type 2 diabetics.
362	17208384	Finally, after delineating critical nodes of insulin and adipokine crosstalk, putative pathways are proposed by which adiponectin and leptin cooperatively regulate systemic insulin sensitivity in accordance to existing fat mass.
363	17208384	By amplifying insulin action downstream of PI3K, leptin exerts negative feedback on insulin signaling via mTOR-dependent pathways that target IRS-1 for serine phosphorylation and protein degradation.
364	17208384	Adiponectin-mediated increments of AMPK activity, on the other hand, may attenuate mTOR signaling, leading to the preservation of insulin sensitivity in periods of increased nutrient availability.
365	17208384	Considering that leptin and adiponectin are inversely associated with BMI, the proposed model provides a plausible explanation for the observation that leptin exerts strong negative feedback on systemic insulin sensitivity, while increasing PIP3 availability.
366	17467844	These insulin actions were modestly inhibited by the application of LY294002, the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, but not completely, suggesting that another mechanism is also involved.
367	17467844	These results may suggest that the extent of AMPK activation may be a tool for insulin receptors to monitor blood glucose level, with which insulin-induced insulin receptor activation determines the way to go negatively or positively toward [Ca(2+)](c).
368	17525164	Activation of 5'-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2.
369	17525164	One of the regulators of the period length is casein kinase Iepsilon (CKIepsilon), which by phosphorylating and inducing the degradation of the circadian clock component, mPer2, shortens the period length.
370	17525164	AMPK phosphorylates Ser-389 of CKIepsilon, resulting in increased CKIepsilon activity and degradation of mPer2.
371	17525164	In peripheral tissues, injection of metformin leads to mPer2 degradation and a phase advance in the circadian expression pattern of clock genes in wild-type mice but not in AMPK alpha2 knock-out mice.
372	17525164	Activation of 5'-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2.
373	17525164	One of the regulators of the period length is casein kinase Iepsilon (CKIepsilon), which by phosphorylating and inducing the degradation of the circadian clock component, mPer2, shortens the period length.
374	17525164	AMPK phosphorylates Ser-389 of CKIepsilon, resulting in increased CKIepsilon activity and degradation of mPer2.
375	17525164	In peripheral tissues, injection of metformin leads to mPer2 degradation and a phase advance in the circadian expression pattern of clock genes in wild-type mice but not in AMPK alpha2 knock-out mice.
376	17560826	Phosphorylation by the mitogen-activated protein kinases (ERK- and p38-MAPK), Protein Kinase A and C (PKA, PKC), AMP Kinase (AMPK) and glycogen synthase kinase-3 (GSK3) affect their activity in a ligand-dependent or -independent manner.
377	17575082	This study tests the hypothesis that AMP kinase (AMPK) activation with metformin directly improves insulin signaling within the blastocyst, leading to improved pregnancy outcomes.
378	17575082	Resulting blastocysts were compared with embryos cocultured with excess IGF-I plus metformin and embryos cultured in control medium for the following: AMPK phosphorylation, insulin-stimulated glucose uptake, and apoptosis.
379	17575082	Compared with control blastocysts, blastocysts exposed to high concentrations of IGF-I showed a decrease in AMPK activation and insulin-stimulated glucose uptake and an increase in the number of apoptotic nuclei.
380	17575082	This study tests the hypothesis that AMP kinase (AMPK) activation with metformin directly improves insulin signaling within the blastocyst, leading to improved pregnancy outcomes.
381	17575082	Resulting blastocysts were compared with embryos cocultured with excess IGF-I plus metformin and embryos cultured in control medium for the following: AMPK phosphorylation, insulin-stimulated glucose uptake, and apoptosis.
382	17575082	Compared with control blastocysts, blastocysts exposed to high concentrations of IGF-I showed a decrease in AMPK activation and insulin-stimulated glucose uptake and an increase in the number of apoptotic nuclei.
383	17575082	This study tests the hypothesis that AMP kinase (AMPK) activation with metformin directly improves insulin signaling within the blastocyst, leading to improved pregnancy outcomes.
384	17575082	Resulting blastocysts were compared with embryos cocultured with excess IGF-I plus metformin and embryos cultured in control medium for the following: AMPK phosphorylation, insulin-stimulated glucose uptake, and apoptosis.
385	17575082	Compared with control blastocysts, blastocysts exposed to high concentrations of IGF-I showed a decrease in AMPK activation and insulin-stimulated glucose uptake and an increase in the number of apoptotic nuclei.
386	17950019	Single nucleotide polymorphisms in genes encoding LKB1 (STK11), TORC2 (CRTC2) and AMPK alpha2-subunit (PRKAA2) and risk of type 2 diabetes.
387	17950019	To examine whether genetic variations in genes encoding components of this signaling pathway contribute to increased susceptibility to type 2 diabetes, we screened STK11 (LKB1) and CRTC2 (TORC2) genes for genetic variants and conducted a case-control study in 1787 unrelated Japanese individuals.
388	17950019	We observed associations of nominal significance with two SNPs, an intronic SNP in the STK11 (rs741765; OR 1.33, 95% CI 1.05-1.67, p=0.017, under a recessive genetic model), and a non-synonymous SNP in the CRTC2 (6909C>T: Arg379Cys; OR 3.01, 95% CI 1.18-7.66, p=0.016, under a dominant model), although neither withstood correction for multiple testing.
389	17950019	Among the three genes investigated herein, gene-gene (SNP-SNP) interaction studies provided evidence for an interaction between STK11 and CRTC2 influencing susceptibility to type 2 diabetes.
390	18266981	Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium.
391	18266981	Homeostasis of blood glucose by insulin involves stimulation of glucose uptake by translocation of glucose transporter Glut-4 from intracellular pool to the caveolar membrane system.
392	18266981	Lipid raft fractions demonstrated decreased expression of Glut-4, Cav-3 (0.4, 0.6-fold) in DM which was increased to 0.75- and 1.1-fold on RSV treatment as compared to control.
393	18266981	Increased phosphorylation of endothelial Nitric Oxide Synthase (eNOS) & Akt was also observed in RSV compared to DM (P<0.05).
394	18266981	Confocal microscopy and coimmunoprecipitation studies demonstrated decreased association of Glut-4/Cav-3 and increased association of Cav-1/eNOS in DM as compared to control and converse results were obtained on RSV treatment.
395	18266981	Our results suggests that the effect of RSV is non-insulin dependent and triggers some of the similar intracellular insulin signalling components in myocardium such as eNOS, Akt through AMPK pathway and also by regulating the caveolin-1 and caveolin-3 status that might play an essential role in Glut-4 translocation and glucose uptake in STZ- induced type-1 diabetic myocardium.
396	18266981	Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium.
397	18266981	Homeostasis of blood glucose by insulin involves stimulation of glucose uptake by translocation of glucose transporter Glut-4 from intracellular pool to the caveolar membrane system.
398	18266981	Lipid raft fractions demonstrated decreased expression of Glut-4, Cav-3 (0.4, 0.6-fold) in DM which was increased to 0.75- and 1.1-fold on RSV treatment as compared to control.
399	18266981	Increased phosphorylation of endothelial Nitric Oxide Synthase (eNOS) & Akt was also observed in RSV compared to DM (P<0.05).
400	18266981	Confocal microscopy and coimmunoprecipitation studies demonstrated decreased association of Glut-4/Cav-3 and increased association of Cav-1/eNOS in DM as compared to control and converse results were obtained on RSV treatment.
401	18266981	Our results suggests that the effect of RSV is non-insulin dependent and triggers some of the similar intracellular insulin signalling components in myocardium such as eNOS, Akt through AMPK pathway and also by regulating the caveolin-1 and caveolin-3 status that might play an essential role in Glut-4 translocation and glucose uptake in STZ- induced type-1 diabetic myocardium.
402	18344204	The cellular nutrient and energy sensors, AMPK and TOR, play a key role in maintaining cellular energy homeostasis.
403	18344204	Like AMPK and TOR, PAS kinase (PASK) is also a nutrient responsive protein kinase.
404	18344204	In cultured pancreatic beta-cells, PASK is activated by elevated glucose concentrations and is required for glucose-stimulated transcription of the insulin gene.
405	18344204	Interestingly, PGC-1 expression and AMPK and TOR activity were not affected in PASK deficient mice, suggesting PASK may exert its metabolic effects through a new mechanism.
406	18344204	The cellular nutrient and energy sensors, AMPK and TOR, play a key role in maintaining cellular energy homeostasis.
407	18344204	Like AMPK and TOR, PAS kinase (PASK) is also a nutrient responsive protein kinase.
408	18344204	In cultured pancreatic beta-cells, PASK is activated by elevated glucose concentrations and is required for glucose-stimulated transcription of the insulin gene.
409	18344204	Interestingly, PGC-1 expression and AMPK and TOR activity were not affected in PASK deficient mice, suggesting PASK may exert its metabolic effects through a new mechanism.
410	18344204	The cellular nutrient and energy sensors, AMPK and TOR, play a key role in maintaining cellular energy homeostasis.
411	18344204	Like AMPK and TOR, PAS kinase (PASK) is also a nutrient responsive protein kinase.
412	18344204	In cultured pancreatic beta-cells, PASK is activated by elevated glucose concentrations and is required for glucose-stimulated transcription of the insulin gene.
413	18344204	Interestingly, PGC-1 expression and AMPK and TOR activity were not affected in PASK deficient mice, suggesting PASK may exert its metabolic effects through a new mechanism.
414	18403917	LKB1 and AMPK and the regulation of skeletal muscle metabolism.
415	18431508	In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens-1 translocation to the membrane.
416	18431508	These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes.
417	18431508	Ad(-/-) mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress.
418	18431508	These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes.
419	18431508	In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens-1 translocation to the membrane.
420	18431508	These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes.
421	18431508	Ad(-/-) mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress.
422	18431508	These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes.
423	18431508	In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens-1 translocation to the membrane.
424	18431508	These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes.
425	18431508	Ad(-/-) mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress.
426	18431508	These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes.
427	18431508	In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens-1 translocation to the membrane.
428	18431508	These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes.
429	18431508	Ad(-/-) mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress.
430	18431508	These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes.
431	18446001	Molecular mechanism of moderate insulin resistance in adiponectin-knockout mice.
432	18446001	Although adiponectin-knockout (adipo(-/-)) mice are known to exhibit insulin resistance, the degrees of insulin resistance and glucose intolerance are unexpectedly only moderate.
433	18446001	In this study, the adipo(-/-) mice showed hepatic, but not muscle, insulin resistance. insulin-stimulated phosphorylation of IRS-1 and IRS-2 was impaired, the IRS-2 protein level was decreased, and insulin-stimulated phosphorylation of Akt was decreased in the liver of the adipo(-/-) mice.
434	18446001	However, the triglyceride content in the liver was not increased in these mice, despite the decrease in the PPARalpha expression involved in lipid combustion, since the expressions of lipogenic genes such as SREBP-1 and SCD-1 were decreased in association with the increased leptin sensitivity.
435	18446001	Consistent with this, the down-regulation SREBP-1 and SCD-1 observed in the adipo(-/-) mice was no longer observed, and the hepatic triglyceride content was significantly increased in the adiponectin leptin double-knockout (adipo(-/-)ob/ob) mice.
436	18446001	On the other hand, the triglyceride content in the skeletal muscle was significantly decreased in the adipo(-/-) mice, probably due to up-regulated AMPK activity associated with the increased leptin sensitivity.
437	18446001	In conclusion, adipo(-/-) mice showed impaired insulin signaling in the liver to cause hepatic insulin resistance, however, no increase in the triglyceride content was observed in either the liver or the skeletal muscle, presumably on account of the increased leptin sensitivity.
438	18626018	Glucose controls CREB activity in islet cells via regulated phosphorylation of TORC2.
439	18626018	Glucose and incretin hormones elicit beta cell insulin secretion and promote synergistic CREB activity by inducing the nuclear relocalization of TORC2 (also known as Crtc2), a coactivator for CREB.
440	18626018	In islet cells under basal conditions when CREB activity is low, TORC2 is phosphorylated and sequestered in the cytoplasm by 14-3-3 proteins.
441	18626018	In response to feeding stimuli, TORC2 is dephosphorylated, enters the nucleus, and binds to CREB located at target gene promoters.
442	18626018	The dephosphorylation of TORC2 at Ser-171 in response to cAMP is insufficient to account for the dynamics of TORC2 localization and CREB activity in islet cells.
443	18626018	Using a cell-based screen of 180 human protein kinases, we identified MARK2, a member of the AMPK family of Ser/Thr kinases, as a Ser-275 kinase that blocks TORC2:CREB activity.
444	18780775	Six weeks of high-fat feeding resulted in reductions in CORE I, COX IV, cytochrome c, HSP60, relative mtDNA copy number, and PGC-1alpha expression.
445	18780775	These changes were not associated with decreases in eNOS and AMPK or increases in markers of oxidative stress.
446	19027847	Niacin bound chromium treatment induces myocardial Glut-4 translocation and caveolar interaction via Akt, AMPK and eNOS phosphorylation in streptozotocin induced diabetic rats after ischemia-reperfusion injury.
447	19027847	Reduced Cav-1 and increased Cav-3 expression along with phosphorylation of Akt, eNOS and AMPK might have resulted in increased Glut-4 translocation in Dia+NBC.
448	19027847	Our results indicate that the cardioprotective effect of NBC is mediated by increased activation of AMPK, Akt and eNOS resulting in increased translocation of Glut-4 to the caveolar raft fractions thereby alleviating the effects of IR injury in the diabetic myocardium.
449	19027847	Niacin bound chromium treatment induces myocardial Glut-4 translocation and caveolar interaction via Akt, AMPK and eNOS phosphorylation in streptozotocin induced diabetic rats after ischemia-reperfusion injury.
450	19027847	Reduced Cav-1 and increased Cav-3 expression along with phosphorylation of Akt, eNOS and AMPK might have resulted in increased Glut-4 translocation in Dia+NBC.
451	19027847	Our results indicate that the cardioprotective effect of NBC is mediated by increased activation of AMPK, Akt and eNOS resulting in increased translocation of Glut-4 to the caveolar raft fractions thereby alleviating the effects of IR injury in the diabetic myocardium.
452	19027847	Niacin bound chromium treatment induces myocardial Glut-4 translocation and caveolar interaction via Akt, AMPK and eNOS phosphorylation in streptozotocin induced diabetic rats after ischemia-reperfusion injury.
453	19027847	Reduced Cav-1 and increased Cav-3 expression along with phosphorylation of Akt, eNOS and AMPK might have resulted in increased Glut-4 translocation in Dia+NBC.
454	19027847	Our results indicate that the cardioprotective effect of NBC is mediated by increased activation of AMPK, Akt and eNOS resulting in increased translocation of Glut-4 to the caveolar raft fractions thereby alleviating the effects of IR injury in the diabetic myocardium.
455	19190261	Since oxidative stress depletes adiponectin and insulin levels, we investigated whether an upregulated heme oxygenase (HO) system would attenuate the oxidative destruction of adiponectin/insulin and improve insulin sensitivity and glucose metabolism in streptozotocin (STZ)-induced type 1 diabetes.
456	19190261	Interestingly, the antidiabetic effects of hemin lasted for 2 mo after termination of therapy and were accompanied by enhanced HO-1 and HO activity of the soleus muscle, along with potentiation of plasma antioxidants like bilirubin, ferritin, and superoxide dismutase, with corresponding elevation of the total antioxidant capacity.
457	19190261	Importantly, hemin abated c-Jun NH2-terminal kinase (JNK), a substance known to inhibit insulin biosynthesis, and suppressed markers/mediators of oxidative stress including 8-isoprostane, nuclear-factor (NF)-kappaB, activating protein (AP)-1, and AP-2 of the soleus muscle.
458	19190261	Correspondingly, hemin increased plasma insulin and potentiated agents implicated in insulin sensitization and insulin signaling such as adiponectin, adenosine monophosphate-activated protein kinase (AMPK), cAMP, cGMP, and glucose transporter (GLUT)4, a protein required for glucose uptake.
459	19208858	The reduction of hyperglycemia was accompanied by enhanced HO-1, HO activity, and cGMP of the soleus muscle, alongside increased plasma bilirubin, ferritin, SOD, total antioxidant capacity, and insulin levels, whereas markers/mediators of oxidative stress like urinary-8-isoprostane and soleus muscle nitrotyrosine, NF-kappaB, and activator protein-1 and -2 were abated.
460	19208858	Furthermore, inhibitors of insulin signaling including soleus muscle glycogen synthase kinase-3 and JNK were reduced, while the insulin-sensitizing adipokine, adiponectin, alongside AMPK were increased.
461	19208858	Correspondingly, hemin improved glucose tolerance, suppressed insulin intolerance, reduced insulin resistance, and overturned the inability of insulin to enhance glucose transporter 4, a protein required for glucose uptake.
462	19208858	The synergistic interaction among HO, adiponectin, and GLUT4 may be explored against insulin-resistant diabetes.
463	19223652	This change in the glucose sensitivity in the presence of insulin was reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (10 nM) but not by the mitogen-activated kinase (MAPK) inhibitor PD-98059 (PD; 50 microM).
464	19223652	Finally, neither the AMPK inhibitor compound C nor the AMPK activator AICAR altered the activity of VMH GE neurons.
465	19223652	These data suggest that insulin attenuates the ability of VMH GE neurons to sense decreased glucose via the PI3K signaling pathway.
466	19228889	Insulin-mediated signal transduction is positively correlated to adiponectin, adenosine monophosphate-activated protein kinase (AMPK), and glucose-transporter-4 (GLUT4) but negatively to oxidative/inflammatory mediators such as nuclear factor-kappaB, activating-protein (AP)-1, AP-2, and c-Jun-N-terminal-kinase.
467	19228889	Although hemeoxygenase (HO) suppresses oxidative insults, its effects on insulin-sensitizing agents like AMPK and GLUT4 remains unclear and were investigated using Goto-Kakizaki rats (GK), a nonobese insulin-resistant type-2 diabetic model.
468	19228889	Interestingly, the antidiabetic was accompanied by a paradoxical increase of insulin alongside the potentiation of insulin-sensitizing agents such as adiponectin, AMPK, and GLUT4 in the gastrocnemius muscle.
469	19228889	Furthermore, hemin enhanced mediators/regulators of insulin signaling like cGMP and cAMP and suppressed oxidative insults by up-regulating HO-1, HO activity, superoxide dismutase, catalase, and the total antioxidant capacity in the gastrocnemius muscle.
470	19228889	Accordingly, oxidative markers/mediators including nuclear factor-kappaB, AP-1, AP-2, c-Jun-N-terminal-kinase, and 8-isoprostane were abated, whereas CrMP annulled the cytoprotective and antidiabetic effects of hemin.
471	19228889	Our study unveils a 3-month enduring antidiabetic effect of hemin and unmasks the synergistic interaction among the HO system, adiponectin, AMPK, and GLUT4 that could be explored to enhance insulin signaling and improve glucose metabolism in insulin-resistant diabetes.
472	19228889	Insulin-mediated signal transduction is positively correlated to adiponectin, adenosine monophosphate-activated protein kinase (AMPK), and glucose-transporter-4 (GLUT4) but negatively to oxidative/inflammatory mediators such as nuclear factor-kappaB, activating-protein (AP)-1, AP-2, and c-Jun-N-terminal-kinase.
473	19228889	Although hemeoxygenase (HO) suppresses oxidative insults, its effects on insulin-sensitizing agents like AMPK and GLUT4 remains unclear and were investigated using Goto-Kakizaki rats (GK), a nonobese insulin-resistant type-2 diabetic model.
474	19228889	Interestingly, the antidiabetic was accompanied by a paradoxical increase of insulin alongside the potentiation of insulin-sensitizing agents such as adiponectin, AMPK, and GLUT4 in the gastrocnemius muscle.
475	19228889	Furthermore, hemin enhanced mediators/regulators of insulin signaling like cGMP and cAMP and suppressed oxidative insults by up-regulating HO-1, HO activity, superoxide dismutase, catalase, and the total antioxidant capacity in the gastrocnemius muscle.
476	19228889	Accordingly, oxidative markers/mediators including nuclear factor-kappaB, AP-1, AP-2, c-Jun-N-terminal-kinase, and 8-isoprostane were abated, whereas CrMP annulled the cytoprotective and antidiabetic effects of hemin.
477	19228889	Our study unveils a 3-month enduring antidiabetic effect of hemin and unmasks the synergistic interaction among the HO system, adiponectin, AMPK, and GLUT4 that could be explored to enhance insulin signaling and improve glucose metabolism in insulin-resistant diabetes.
478	19228889	Insulin-mediated signal transduction is positively correlated to adiponectin, adenosine monophosphate-activated protein kinase (AMPK), and glucose-transporter-4 (GLUT4) but negatively to oxidative/inflammatory mediators such as nuclear factor-kappaB, activating-protein (AP)-1, AP-2, and c-Jun-N-terminal-kinase.
479	19228889	Although hemeoxygenase (HO) suppresses oxidative insults, its effects on insulin-sensitizing agents like AMPK and GLUT4 remains unclear and were investigated using Goto-Kakizaki rats (GK), a nonobese insulin-resistant type-2 diabetic model.
480	19228889	Interestingly, the antidiabetic was accompanied by a paradoxical increase of insulin alongside the potentiation of insulin-sensitizing agents such as adiponectin, AMPK, and GLUT4 in the gastrocnemius muscle.
481	19228889	Furthermore, hemin enhanced mediators/regulators of insulin signaling like cGMP and cAMP and suppressed oxidative insults by up-regulating HO-1, HO activity, superoxide dismutase, catalase, and the total antioxidant capacity in the gastrocnemius muscle.
482	19228889	Accordingly, oxidative markers/mediators including nuclear factor-kappaB, AP-1, AP-2, c-Jun-N-terminal-kinase, and 8-isoprostane were abated, whereas CrMP annulled the cytoprotective and antidiabetic effects of hemin.
483	19228889	Our study unveils a 3-month enduring antidiabetic effect of hemin and unmasks the synergistic interaction among the HO system, adiponectin, AMPK, and GLUT4 that could be explored to enhance insulin signaling and improve glucose metabolism in insulin-resistant diabetes.
484	19228889	Insulin-mediated signal transduction is positively correlated to adiponectin, adenosine monophosphate-activated protein kinase (AMPK), and glucose-transporter-4 (GLUT4) but negatively to oxidative/inflammatory mediators such as nuclear factor-kappaB, activating-protein (AP)-1, AP-2, and c-Jun-N-terminal-kinase.
485	19228889	Although hemeoxygenase (HO) suppresses oxidative insults, its effects on insulin-sensitizing agents like AMPK and GLUT4 remains unclear and were investigated using Goto-Kakizaki rats (GK), a nonobese insulin-resistant type-2 diabetic model.
486	19228889	Interestingly, the antidiabetic was accompanied by a paradoxical increase of insulin alongside the potentiation of insulin-sensitizing agents such as adiponectin, AMPK, and GLUT4 in the gastrocnemius muscle.
487	19228889	Furthermore, hemin enhanced mediators/regulators of insulin signaling like cGMP and cAMP and suppressed oxidative insults by up-regulating HO-1, HO activity, superoxide dismutase, catalase, and the total antioxidant capacity in the gastrocnemius muscle.
488	19228889	Accordingly, oxidative markers/mediators including nuclear factor-kappaB, AP-1, AP-2, c-Jun-N-terminal-kinase, and 8-isoprostane were abated, whereas CrMP annulled the cytoprotective and antidiabetic effects of hemin.
489	19228889	Our study unveils a 3-month enduring antidiabetic effect of hemin and unmasks the synergistic interaction among the HO system, adiponectin, AMPK, and GLUT4 that could be explored to enhance insulin signaling and improve glucose metabolism in insulin-resistant diabetes.
490	19252305	The findings from adenosine monophosphate-activated kinase (AMPK) activation and glucose transport protein4 (GLUT4) and GLUT1 over-expression revealed certain characteristics of compounds 2--5.
491	19252305	It was concluded that T. scandens and its constituents exerted highly desirable activities on type 2 diabetes mellitus treatment since they significantly stimulated the uptake of glucose, AMPK phosphorylation, GLUT4 and GLUT1 mRNA expressions and PTP1B inhibition in L6 myotubes.
492	19252305	The findings from adenosine monophosphate-activated kinase (AMPK) activation and glucose transport protein4 (GLUT4) and GLUT1 over-expression revealed certain characteristics of compounds 2--5.
493	19252305	It was concluded that T. scandens and its constituents exerted highly desirable activities on type 2 diabetes mellitus treatment since they significantly stimulated the uptake of glucose, AMPK phosphorylation, GLUT4 and GLUT1 mRNA expressions and PTP1B inhibition in L6 myotubes.
494	19276888	PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure.
495	19318515	We hypothesized that beta-GPA feeding would result in a preferential activation of p38 MAPK and AMPK signaling and reductions in RIP140 protein content in triceps but not soleus muscle.
496	19318515	Differences in the response of mitochondrial proteins to beta-GPA feeding did not seem to be related to a differential activation of p38 MAPK and AMPK signaling pathways or discrepancies in the induction of PPARgamma coactivator (PGC)-1alpha and -1beta.
497	19318515	Collectively our results indicate that chronic reductions in high-energy phosphates lead to the activation of p38 MAPK and AMPK signaling and increases in the expression of PGC-1alpha and -1beta in both soleus and triceps muscles.
498	19318515	We hypothesized that beta-GPA feeding would result in a preferential activation of p38 MAPK and AMPK signaling and reductions in RIP140 protein content in triceps but not soleus muscle.
499	19318515	Differences in the response of mitochondrial proteins to beta-GPA feeding did not seem to be related to a differential activation of p38 MAPK and AMPK signaling pathways or discrepancies in the induction of PPARgamma coactivator (PGC)-1alpha and -1beta.
500	19318515	Collectively our results indicate that chronic reductions in high-energy phosphates lead to the activation of p38 MAPK and AMPK signaling and increases in the expression of PGC-1alpha and -1beta in both soleus and triceps muscles.
501	19318515	We hypothesized that beta-GPA feeding would result in a preferential activation of p38 MAPK and AMPK signaling and reductions in RIP140 protein content in triceps but not soleus muscle.
502	19318515	Differences in the response of mitochondrial proteins to beta-GPA feeding did not seem to be related to a differential activation of p38 MAPK and AMPK signaling pathways or discrepancies in the induction of PPARgamma coactivator (PGC)-1alpha and -1beta.
503	19318515	Collectively our results indicate that chronic reductions in high-energy phosphates lead to the activation of p38 MAPK and AMPK signaling and increases in the expression of PGC-1alpha and -1beta in both soleus and triceps muscles.
504	19391163	Potential regulators include Ca(2+) (via CaMK's and/or CaMKK), AMPK, ROS, and NO signaling, with some redundancy likely to be evident within the system.
505	19440050	Nutrient-sensing protein kinases, such as AMPK and mTOR, play a pivotal role in metabolic regulation and are promising therapeutic targets for the treatment of disease.
506	19440050	The two yeast PAS kinase homologs, Psk1 and Psk2, are activated by two stimuli, cell integrity stress and nonfermentative carbon sources.
507	19477471	Increased expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor-1, cytochrome c, cytochrome c oxidase-4, and glucose transporter 4 by KRG treatment indicates that activated AMPK also enhanced mitochondrial biogenesis and glucose utilization in skeletal muscle.
508	19477471	Although these findings suggest that KRG is likely to have beneficial effects on the amelioration of insulin resistance and the prevention of T2DM through the activation of AMPK, further clinical studies are required to evaluate the use of KRG as a supplementary agent for T2DM.
509	19477471	Increased expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor-1, cytochrome c, cytochrome c oxidase-4, and glucose transporter 4 by KRG treatment indicates that activated AMPK also enhanced mitochondrial biogenesis and glucose utilization in skeletal muscle.
510	19477471	Although these findings suggest that KRG is likely to have beneficial effects on the amelioration of insulin resistance and the prevention of T2DM through the activation of AMPK, further clinical studies are required to evaluate the use of KRG as a supplementary agent for T2DM.
511	19528236	Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues.
512	19528236	PTP1B(-/-) mice are resistant to diet-induced obesity due to leptin hypersensitivity and consequent increased energy expenditure.
513	19528236	AMPK is an important mediator of leptin's metabolic effects.
514	19528236	We find that alpha1 and alpha2 AMPK activity are elevated and acetyl-coenzyme A carboxylase activity is decreased in the muscle and brown adipose tissue (BAT) of PTP1B(-/-) mice.
515	19528236	The effects of PTP1B deficiency on alpha2, but not alpha1, AMPK activity in BAT and muscle are neuronally mediated, as they are present in neuron- but not muscle-specific PTP1B(-/-) mice.
516	19528236	In addition, AMPK activity is decreased in the hypothalamic nuclei of neuronal and whole-body PTP1B(-/-) mice, accompanied by alterations in neuropeptide expression that are indicative of enhanced leptin sensitivity.
517	19528236	Furthermore, AMPK target genes regulating mitochondrial biogenesis, fatty acid oxidation, and energy expenditure are induced with PTP1B inhibition, resulting in increased mitochondrial content in BAT and conversion to a more oxidative muscle fiber type.
518	19528236	Thus, neuronal PTP1B inhibition results in decreased hypothalamic AMPK activity, isoform-specific AMPK activation in peripheral tissues, and downstream gene expression changes that promote leanness and increased energy expenditure.
519	19528236	Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity likely involves the coordinated regulation of AMPK in hypothalamus and peripheral tissues.
520	19528236	Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues.
521	19528236	PTP1B(-/-) mice are resistant to diet-induced obesity due to leptin hypersensitivity and consequent increased energy expenditure.
522	19528236	AMPK is an important mediator of leptin's metabolic effects.
523	19528236	We find that alpha1 and alpha2 AMPK activity are elevated and acetyl-coenzyme A carboxylase activity is decreased in the muscle and brown adipose tissue (BAT) of PTP1B(-/-) mice.
524	19528236	The effects of PTP1B deficiency on alpha2, but not alpha1, AMPK activity in BAT and muscle are neuronally mediated, as they are present in neuron- but not muscle-specific PTP1B(-/-) mice.
525	19528236	In addition, AMPK activity is decreased in the hypothalamic nuclei of neuronal and whole-body PTP1B(-/-) mice, accompanied by alterations in neuropeptide expression that are indicative of enhanced leptin sensitivity.
526	19528236	Furthermore, AMPK target genes regulating mitochondrial biogenesis, fatty acid oxidation, and energy expenditure are induced with PTP1B inhibition, resulting in increased mitochondrial content in BAT and conversion to a more oxidative muscle fiber type.
527	19528236	Thus, neuronal PTP1B inhibition results in decreased hypothalamic AMPK activity, isoform-specific AMPK activation in peripheral tissues, and downstream gene expression changes that promote leanness and increased energy expenditure.
528	19528236	Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity likely involves the coordinated regulation of AMPK in hypothalamus and peripheral tissues.
529	19528236	Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues.
530	19528236	PTP1B(-/-) mice are resistant to diet-induced obesity due to leptin hypersensitivity and consequent increased energy expenditure.
531	19528236	AMPK is an important mediator of leptin's metabolic effects.
532	19528236	We find that alpha1 and alpha2 AMPK activity are elevated and acetyl-coenzyme A carboxylase activity is decreased in the muscle and brown adipose tissue (BAT) of PTP1B(-/-) mice.
533	19528236	The effects of PTP1B deficiency on alpha2, but not alpha1, AMPK activity in BAT and muscle are neuronally mediated, as they are present in neuron- but not muscle-specific PTP1B(-/-) mice.
534	19528236	In addition, AMPK activity is decreased in the hypothalamic nuclei of neuronal and whole-body PTP1B(-/-) mice, accompanied by alterations in neuropeptide expression that are indicative of enhanced leptin sensitivity.
535	19528236	Furthermore, AMPK target genes regulating mitochondrial biogenesis, fatty acid oxidation, and energy expenditure are induced with PTP1B inhibition, resulting in increased mitochondrial content in BAT and conversion to a more oxidative muscle fiber type.
536	19528236	Thus, neuronal PTP1B inhibition results in decreased hypothalamic AMPK activity, isoform-specific AMPK activation in peripheral tissues, and downstream gene expression changes that promote leanness and increased energy expenditure.
537	19528236	Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity likely involves the coordinated regulation of AMPK in hypothalamus and peripheral tissues.
538	19528236	Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues.
539	19528236	PTP1B(-/-) mice are resistant to diet-induced obesity due to leptin hypersensitivity and consequent increased energy expenditure.
540	19528236	AMPK is an important mediator of leptin's metabolic effects.
541	19528236	We find that alpha1 and alpha2 AMPK activity are elevated and acetyl-coenzyme A carboxylase activity is decreased in the muscle and brown adipose tissue (BAT) of PTP1B(-/-) mice.
542	19528236	The effects of PTP1B deficiency on alpha2, but not alpha1, AMPK activity in BAT and muscle are neuronally mediated, as they are present in neuron- but not muscle-specific PTP1B(-/-) mice.
543	19528236	In addition, AMPK activity is decreased in the hypothalamic nuclei of neuronal and whole-body PTP1B(-/-) mice, accompanied by alterations in neuropeptide expression that are indicative of enhanced leptin sensitivity.
544	19528236	Furthermore, AMPK target genes regulating mitochondrial biogenesis, fatty acid oxidation, and energy expenditure are induced with PTP1B inhibition, resulting in increased mitochondrial content in BAT and conversion to a more oxidative muscle fiber type.
545	19528236	Thus, neuronal PTP1B inhibition results in decreased hypothalamic AMPK activity, isoform-specific AMPK activation in peripheral tissues, and downstream gene expression changes that promote leanness and increased energy expenditure.
546	19528236	Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity likely involves the coordinated regulation of AMPK in hypothalamus and peripheral tissues.
547	19528236	Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues.
548	19528236	PTP1B(-/-) mice are resistant to diet-induced obesity due to leptin hypersensitivity and consequent increased energy expenditure.
549	19528236	AMPK is an important mediator of leptin's metabolic effects.
550	19528236	We find that alpha1 and alpha2 AMPK activity are elevated and acetyl-coenzyme A carboxylase activity is decreased in the muscle and brown adipose tissue (BAT) of PTP1B(-/-) mice.
551	19528236	The effects of PTP1B deficiency on alpha2, but not alpha1, AMPK activity in BAT and muscle are neuronally mediated, as they are present in neuron- but not muscle-specific PTP1B(-/-) mice.
552	19528236	In addition, AMPK activity is decreased in the hypothalamic nuclei of neuronal and whole-body PTP1B(-/-) mice, accompanied by alterations in neuropeptide expression that are indicative of enhanced leptin sensitivity.
553	19528236	Furthermore, AMPK target genes regulating mitochondrial biogenesis, fatty acid oxidation, and energy expenditure are induced with PTP1B inhibition, resulting in increased mitochondrial content in BAT and conversion to a more oxidative muscle fiber type.
554	19528236	Thus, neuronal PTP1B inhibition results in decreased hypothalamic AMPK activity, isoform-specific AMPK activation in peripheral tissues, and downstream gene expression changes that promote leanness and increased energy expenditure.
555	19528236	Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity likely involves the coordinated regulation of AMPK in hypothalamus and peripheral tissues.
556	19528236	Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues.
557	19528236	PTP1B(-/-) mice are resistant to diet-induced obesity due to leptin hypersensitivity and consequent increased energy expenditure.
558	19528236	AMPK is an important mediator of leptin's metabolic effects.
559	19528236	We find that alpha1 and alpha2 AMPK activity are elevated and acetyl-coenzyme A carboxylase activity is decreased in the muscle and brown adipose tissue (BAT) of PTP1B(-/-) mice.
560	19528236	The effects of PTP1B deficiency on alpha2, but not alpha1, AMPK activity in BAT and muscle are neuronally mediated, as they are present in neuron- but not muscle-specific PTP1B(-/-) mice.
561	19528236	In addition, AMPK activity is decreased in the hypothalamic nuclei of neuronal and whole-body PTP1B(-/-) mice, accompanied by alterations in neuropeptide expression that are indicative of enhanced leptin sensitivity.
562	19528236	Furthermore, AMPK target genes regulating mitochondrial biogenesis, fatty acid oxidation, and energy expenditure are induced with PTP1B inhibition, resulting in increased mitochondrial content in BAT and conversion to a more oxidative muscle fiber type.
563	19528236	Thus, neuronal PTP1B inhibition results in decreased hypothalamic AMPK activity, isoform-specific AMPK activation in peripheral tissues, and downstream gene expression changes that promote leanness and increased energy expenditure.
564	19528236	Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity likely involves the coordinated regulation of AMPK in hypothalamus and peripheral tissues.
565	19528236	Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues.
566	19528236	PTP1B(-/-) mice are resistant to diet-induced obesity due to leptin hypersensitivity and consequent increased energy expenditure.
567	19528236	AMPK is an important mediator of leptin's metabolic effects.
568	19528236	We find that alpha1 and alpha2 AMPK activity are elevated and acetyl-coenzyme A carboxylase activity is decreased in the muscle and brown adipose tissue (BAT) of PTP1B(-/-) mice.
569	19528236	The effects of PTP1B deficiency on alpha2, but not alpha1, AMPK activity in BAT and muscle are neuronally mediated, as they are present in neuron- but not muscle-specific PTP1B(-/-) mice.
570	19528236	In addition, AMPK activity is decreased in the hypothalamic nuclei of neuronal and whole-body PTP1B(-/-) mice, accompanied by alterations in neuropeptide expression that are indicative of enhanced leptin sensitivity.
571	19528236	Furthermore, AMPK target genes regulating mitochondrial biogenesis, fatty acid oxidation, and energy expenditure are induced with PTP1B inhibition, resulting in increased mitochondrial content in BAT and conversion to a more oxidative muscle fiber type.
572	19528236	Thus, neuronal PTP1B inhibition results in decreased hypothalamic AMPK activity, isoform-specific AMPK activation in peripheral tissues, and downstream gene expression changes that promote leanness and increased energy expenditure.
573	19528236	Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity likely involves the coordinated regulation of AMPK in hypothalamus and peripheral tissues.
574	19528236	Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues.
575	19528236	PTP1B(-/-) mice are resistant to diet-induced obesity due to leptin hypersensitivity and consequent increased energy expenditure.
576	19528236	AMPK is an important mediator of leptin's metabolic effects.
577	19528236	We find that alpha1 and alpha2 AMPK activity are elevated and acetyl-coenzyme A carboxylase activity is decreased in the muscle and brown adipose tissue (BAT) of PTP1B(-/-) mice.
578	19528236	The effects of PTP1B deficiency on alpha2, but not alpha1, AMPK activity in BAT and muscle are neuronally mediated, as they are present in neuron- but not muscle-specific PTP1B(-/-) mice.
579	19528236	In addition, AMPK activity is decreased in the hypothalamic nuclei of neuronal and whole-body PTP1B(-/-) mice, accompanied by alterations in neuropeptide expression that are indicative of enhanced leptin sensitivity.
580	19528236	Furthermore, AMPK target genes regulating mitochondrial biogenesis, fatty acid oxidation, and energy expenditure are induced with PTP1B inhibition, resulting in increased mitochondrial content in BAT and conversion to a more oxidative muscle fiber type.
581	19528236	Thus, neuronal PTP1B inhibition results in decreased hypothalamic AMPK activity, isoform-specific AMPK activation in peripheral tissues, and downstream gene expression changes that promote leanness and increased energy expenditure.
582	19528236	Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity likely involves the coordinated regulation of AMPK in hypothalamus and peripheral tissues.
583	19557293	We have recently discovered a new class of hydrophobic D-xylose derivatives that activates AMPK in skeletal muscles in a non insulin-dependent manner.
584	19557293	One of these derivatives (2,4;3,5-dibenzylidene-D-xylose-diethyl-dithioacetal) stimulates the rate of hexose transport in skeletal muscle cells by increasing the abundance of glucose transporter-4 (GLUT-4) in the plasma membrane through activation of AMPK.
585	19557293	We have recently discovered a new class of hydrophobic D-xylose derivatives that activates AMPK in skeletal muscles in a non insulin-dependent manner.
586	19557293	One of these derivatives (2,4;3,5-dibenzylidene-D-xylose-diethyl-dithioacetal) stimulates the rate of hexose transport in skeletal muscle cells by increasing the abundance of glucose transporter-4 (GLUT-4) in the plasma membrane through activation of AMPK.
587	19594306	We found that metformin administration both in vivo and in vitro caused an increase in alkaline phosphatase activity, type I collagen synthesis, osteocalcin expression, and extracellular calcium deposition of BMPCs.
588	19594306	In conclusion, our results indicate that metformin causes an osteogenic effect both in vivo and in vitro, possibly mediated by Runx2/Cbfa1 and AMPK activation, suggesting a possible action of metformin in a shift toward the osteoblastic differentiation of BMPCs.
589	19629071	LKB1 encodes a serine-threonine kinase that directly phosphorylates and activates AMPK, a central metabolic sensor.
590	19635557	High glucose-induced oxidative stress alters estrogen effects on ERalpha and ERbeta in human endothelial cells: reversal by AMPK activator.
591	19635557	In this study, we hypothesized that high glucose conditions would alter the regulation of the estrogen receptors (ERs), ERalpha and ERbeta, in endothelial cells, possibly through increased oxidative stress.
592	19635557	The role of the AMPK activator AICAR was examined on modulating the effects of high glucose.
593	19635557	Protein levels of estrogen receptors, ERalpha and ERbeta, were measured through western blotting.
594	19635557	Under normal glucose, E2 increased the levels of ERalpha relative ERbeta; however, high glucose reversed the estrogen effects on endothelial ER expression.
595	19635557	High glucose-induced oxidative stress alters estrogen effects on ERalpha and ERbeta in human endothelial cells: reversal by AMPK activator.
596	19635557	In this study, we hypothesized that high glucose conditions would alter the regulation of the estrogen receptors (ERs), ERalpha and ERbeta, in endothelial cells, possibly through increased oxidative stress.
597	19635557	The role of the AMPK activator AICAR was examined on modulating the effects of high glucose.
598	19635557	Protein levels of estrogen receptors, ERalpha and ERbeta, were measured through western blotting.
599	19635557	Under normal glucose, E2 increased the levels of ERalpha relative ERbeta; however, high glucose reversed the estrogen effects on endothelial ER expression.
600	19699714	Consistent with the increase in glucose uptake, Rg3 stimulated the phosphorylation of IRS-1 and Akt.
601	19699714	Interestingly, Rg3 dramatically increased IRS-1 protein levels, while the protein level of Akt was not affected.
602	19699714	Rg3 regulated IRS-1 expression at the transcriptional level and also increased the level of GLUT4 mRNA.
603	19699714	In addition, we found that this effect of Rg3 on insulin signaling was not mediated by the AMPK pathway.
604	19699714	In conclusion, these results suggest that Rg3 improves insulin signaling and glucose uptake primarily by stimulating the expression of IRS-1 and GLUT4.
605	19769946	DHPO (20mg/kg/d i.p. for 21 days) attenuated fasting blood glucose, improved glucose disposal and corrected dyslipidemia in genetic (leptin deficient, ob/ob) and dietary (high-fat-fed) mouse models of insulin resistance.
606	19769946	The increase in 2DG-uptake was associated with an increase in the phosphorylation of AMPK (thr-172) and its downstream effector acetyl-CoA carboxylase without any changes in the phosphorylation of Akt of insulin receptor.
607	19769946	The AMPK inhibitor, compound C attenuated DHPO-induced glucose-uptake whereas the PI3-kinase inhibitor Wortmannin was less effective.
608	19769946	DHPO (20mg/kg/d i.p. for 21 days) attenuated fasting blood glucose, improved glucose disposal and corrected dyslipidemia in genetic (leptin deficient, ob/ob) and dietary (high-fat-fed) mouse models of insulin resistance.
609	19769946	The increase in 2DG-uptake was associated with an increase in the phosphorylation of AMPK (thr-172) and its downstream effector acetyl-CoA carboxylase without any changes in the phosphorylation of Akt of insulin receptor.
610	19769946	The AMPK inhibitor, compound C attenuated DHPO-induced glucose-uptake whereas the PI3-kinase inhibitor Wortmannin was less effective.
611	20090912	Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1.
612	20090912	Energy sensor AMPK and AMPK-activating kinase LKB1, which are activated in mammals by metformin treatment, are essential for health benefits in C. elegans, suggesting that metformin engages a metabolic loop conserved across phyla.
613	20090912	Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1.
614	20090912	Energy sensor AMPK and AMPK-activating kinase LKB1, which are activated in mammals by metformin treatment, are essential for health benefits in C. elegans, suggesting that metformin engages a metabolic loop conserved across phyla.
615	20133456	Sequential activation of p38MAPK and LKB1-AMPK-tuberous sclerosis complex 2 (TSC2) as well as significant attenuation of ERK1/2 and mammalian target of rapamycin (mTOR)-p70 S6 kinase 1 (p70S6K1) activation was observed through the brown differentiation process.
616	20133456	An in vivo study showed that prolonged 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)-induced AMPK activation increases uncoupling protein 1 expression and induces an accumulation of brown adipocytes in white adipose tissue (WAT), as revealed by immunohistology.
617	20142099	LKB1, the main upstream AMPK kinase (AMPKK) in peripheral tissues, was redistributed from the nucleus into the cytoplasm of cells treated with SU6656 and in cells expressing a kinase-deficient, but not a constitutively kinase-active, Fyn mutant.
618	20142099	Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residues, and mutations of these sites resulted in LKB1 export into the cytoplasm and increased AMPK phosphorylation.
619	20142099	These data demonstrate a crosstalk between Fyn tyrosine kinase and the AMPK energy-sensing pathway, through Fyn-dependent regulation of the AMPK upstream activator LKB1.
620	20142099	LKB1, the main upstream AMPK kinase (AMPKK) in peripheral tissues, was redistributed from the nucleus into the cytoplasm of cells treated with SU6656 and in cells expressing a kinase-deficient, but not a constitutively kinase-active, Fyn mutant.
621	20142099	Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residues, and mutations of these sites resulted in LKB1 export into the cytoplasm and increased AMPK phosphorylation.
622	20142099	These data demonstrate a crosstalk between Fyn tyrosine kinase and the AMPK energy-sensing pathway, through Fyn-dependent regulation of the AMPK upstream activator LKB1.
623	20142099	LKB1, the main upstream AMPK kinase (AMPKK) in peripheral tissues, was redistributed from the nucleus into the cytoplasm of cells treated with SU6656 and in cells expressing a kinase-deficient, but not a constitutively kinase-active, Fyn mutant.
624	20142099	Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residues, and mutations of these sites resulted in LKB1 export into the cytoplasm and increased AMPK phosphorylation.
625	20142099	These data demonstrate a crosstalk between Fyn tyrosine kinase and the AMPK energy-sensing pathway, through Fyn-dependent regulation of the AMPK upstream activator LKB1.
626	20357764	Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1.
627	20357764	Here we provide evidence that adiponectin induces extracellular Ca(2+) influx by adiponectin receptor 1 (AdipoR1), which was necessary for subsequent activation of Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta), AMPK and SIRT1, increased expression and decreased acetylation of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), and increased mitochondria in myocytes.
628	20357764	Moreover, muscle-specific disruption of AdipoR1 suppressed the adiponectin-mediated increase in intracellular Ca(2+) concentration, and decreased the activation of CaMKK, AMPK and SIRT1 by adiponectin.
629	20357764	Suppression of AdipoR1 also resulted in decreased PGC-1alpha expression and deacetylation, decreased mitochondrial content and enzymes, decreased oxidative type I myofibres, and decreased oxidative stress-detoxifying enzymes in skeletal muscle, which were associated with insulin resistance and decreased exercise endurance.
630	20357764	Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes.
631	20357764	Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1.
632	20357764	Here we provide evidence that adiponectin induces extracellular Ca(2+) influx by adiponectin receptor 1 (AdipoR1), which was necessary for subsequent activation of Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta), AMPK and SIRT1, increased expression and decreased acetylation of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), and increased mitochondria in myocytes.
633	20357764	Moreover, muscle-specific disruption of AdipoR1 suppressed the adiponectin-mediated increase in intracellular Ca(2+) concentration, and decreased the activation of CaMKK, AMPK and SIRT1 by adiponectin.
634	20357764	Suppression of AdipoR1 also resulted in decreased PGC-1alpha expression and deacetylation, decreased mitochondrial content and enzymes, decreased oxidative type I myofibres, and decreased oxidative stress-detoxifying enzymes in skeletal muscle, which were associated with insulin resistance and decreased exercise endurance.
635	20357764	Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes.
636	20357764	Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1.
637	20357764	Here we provide evidence that adiponectin induces extracellular Ca(2+) influx by adiponectin receptor 1 (AdipoR1), which was necessary for subsequent activation of Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta), AMPK and SIRT1, increased expression and decreased acetylation of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), and increased mitochondria in myocytes.
638	20357764	Moreover, muscle-specific disruption of AdipoR1 suppressed the adiponectin-mediated increase in intracellular Ca(2+) concentration, and decreased the activation of CaMKK, AMPK and SIRT1 by adiponectin.
639	20357764	Suppression of AdipoR1 also resulted in decreased PGC-1alpha expression and deacetylation, decreased mitochondrial content and enzymes, decreased oxidative type I myofibres, and decreased oxidative stress-detoxifying enzymes in skeletal muscle, which were associated with insulin resistance and decreased exercise endurance.
640	20357764	Decreased levels of adiponectin and AdipoR1 in obesity may have causal roles in mitochondrial dysfunction and insulin resistance seen in diabetes.
641	20371735	PGC-1alpha regulation by exercise training and its influences on muscle function and insulin sensitivity.
642	20371735	The peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) is a major regulator of exercise-induced phenotypic adaptation and substrate utilization.
643	20371735	We provide an overview of 1) the role of PGC-1alpha in exercise-mediated muscle adaptation and 2) the possible insulin-sensitizing role of PGC-1alpha.
644	20371735	To these ends, the following questions are addressed. 1) How is PGC-1alpha regulated, 2) what adaptations are indeed dependent on PGC-1alpha action, 3) is PGC-1alpha altered in insulin resistance, and 4) are PGC-1alpha-knockout and -transgenic mice suitable models for examining therapeutic potential of this coactivator?
645	20371735	In skeletal muscle, an orchestrated signaling network, including Ca(2+)-dependent pathways, reactive oxygen species (ROS), nitric oxide (NO), AMP-dependent protein kinase (AMPK), and p38 MAPK, is involved in the control of contractile protein expression, angiogenesis, mitochondrial biogenesis, and other adaptations.
646	20371735	However, the p38gamma MAPK/PGC-1alpha regulatory axis has been confirmed to be required for exercise-induced angiogenesis and mitochondrial biogenesis but not for fiber type transformation.
647	20371735	With respect to a potential insulin-sensitizing role of PGC-1alpha, human studies on type 2 diabetes suggest that PGC-1alpha and its target genes are only modestly downregulated (< or =34%).
648	20371735	However, studies in PGC-1alpha-knockout or PGC-1alpha-transgenic mice have provided unexpected anomalies, which appear to suggest that PGC-1alpha does not have an insulin-sensitizing role.
649	20371735	In contrast, a modest ( approximately 25%) upregulation of PGC-1alpha, within physiological limits, does improve mitochondrial biogenesis, fatty acid oxidation, and insulin sensitivity in healthy and insulin-resistant skeletal muscle.
650	20371735	Taken altogether, there is substantial evidence that the p38gamma MAPK-PGC-1alpha regulatory axis is critical for exercise-induced metabolic adaptations in skeletal muscle, and strategies that upregulate PGC-1alpha, within physiological limits, have revealed its insulin-sensitizing effects.
651	20393162	Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment.
652	20393162	Additionally, given that AMPK-activating drugs are widely prescribed for their insulin-sensitizing effects, we sought to determine whether 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR)-stimulated AMPK activation could prevent or reverse the deleterious effects of lipid on insulin signaling.
653	20393162	We found that a 1-h palmitate incubation in lean myotubes reduced (P < 0.05) insulin-stimulated phosphoprotein kinase B (Akt), Akt substrate 160 (AS160), and inhibitory factor kappaBalpha (IkappaBalpha) mass, all of which were prevented with AICAR inclusion.
654	20393162	With a longer incubation, we observed that myotubes from morbidly obese individuals appear to be largely resistant to the detrimental effects of 16 h lipid exposure as was evident, in contrast to the lean, by the absence of a reduction in insulin-stimulated insulin receptor substrate (IRS)-1 Tyr phosphorylation, phospho-Akt, and phospho-AS160 (P < 0.05).
655	20393162	Furthermore, 16 h lipid exposure significantly reduced IkappaBalpha levels and increased phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and IRS1-Ser(312) in lean myotubes only (P < 0.05).
656	20393162	Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes.
657	20559023	At the cellular level, this combination leads to p53- and AMPK-dependent apoptosis.
658	20580385	Treatment of HGMEC with fenofibrate resulted in transient activation of adenosine monophosphate-activated protein kinase (AMPK), thereby inducing the phosphorylation of Akt and endothelial nitric oxide synthase, leading to nitric oxide production.
659	20663986	Fenofibrate stimulated the phosphorylation of AMPK and eNOS in the ischemic muscles in WT mice but not in APN-KO mice.
660	20663986	Our observations suggest that fenofibrate could promote revascularization in response to ischemia through adiponectin-dependent AMPK signaling.
661	20663986	Fenofibrate stimulated the phosphorylation of AMPK and eNOS in the ischemic muscles in WT mice but not in APN-KO mice.
662	20663986	Our observations suggest that fenofibrate could promote revascularization in response to ischemia through adiponectin-dependent AMPK signaling.
663	20682696	Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle.
664	20713714	Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle.
665	20713714	Muscle-specific knockout of LKB1, an upstream kinase for AMPK and AMPK-related protein kinases, significantly inhibited contraction-stimulated glucose transport.
666	20713714	Muscle contraction increased sucrose nonfermenting AMPK-related kinase (SNARK) activity, an effect blunted in the muscle-specific LKB1 knockout mice.
667	20713714	Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle.
668	20713714	Muscle-specific knockout of LKB1, an upstream kinase for AMPK and AMPK-related protein kinases, significantly inhibited contraction-stimulated glucose transport.
669	20713714	Muscle contraction increased sucrose nonfermenting AMPK-related kinase (SNARK) activity, an effect blunted in the muscle-specific LKB1 knockout mice.
670	20713714	Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle.
671	20713714	Muscle-specific knockout of LKB1, an upstream kinase for AMPK and AMPK-related protein kinases, significantly inhibited contraction-stimulated glucose transport.
672	20713714	Muscle contraction increased sucrose nonfermenting AMPK-related kinase (SNARK) activity, an effect blunted in the muscle-specific LKB1 knockout mice.
673	20739683	Cannabinoid receptor stimulation impairs mitochondrial biogenesis in mouse white adipose tissue, muscle, and liver: the role of eNOS, p38 MAPK, and AMPK pathways.
674	20798864	Metformin Improves Insulin Signaling in Obese Rats via Reduced IKKbeta Action in a Fiber-Type Specific Manner.
675	20798864	The aim of this study was to (1) determine the ability of metformin to attenuate IKKbeta action, (2) determine whether changes in AMPK activity are associated with changes in IKKbeta action in skeletal muscle, and (3) examine whether changes in AMPK and IKKbeta function are consistent with improved insulin signaling.
676	20798864	Further, metformin increased IkappaBalpha levels in both WG (150%) and RG (67%) of obese rats, indicative of reduced IKKbeta activity (P < .05), and was associated with reduced IRS1-pSer(307) (30%) in the WG of obese rats (P < .02).
677	20798864	From these data we conclude that metformin treatment appears to exert an inhibitory influence on skeletal muscle IKKbeta activity, as evidenced by elevated IkappaBalpha levels and reduced IRS1-Ser(307) phosphorylation in a fiber-type specific manner.
678	20813966	This Commentary discusses how suppressor of glucose by autophagy (SOGA) contributes to adiponectin-mediated insulin-dependent inhibition of autophagy during the activation of adenosine monophosphate kinase (AMPK).
679	20823563	Moreover, 7-O-MA stimulated the reactivation of insulin-mediated phosphorylation of phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB) and adenosine 5'-monophosphate-activated protein kinase (AMPK) in high glucose-induced, insulin-resistant HepG2 cells, and this effect was blocked by either LY294002, a PI3K inhibitor, or compound C, an AMPK inhibitor.
680	20823563	Therefore, these results suggest that 7-O-MA might stimulate glucose uptake via PPARgamma2 activation and improve insulin resistance via PI3K and AMPK-dependent pathways, and be a potential candidate for the management of type 2 DM.
681	20823563	Moreover, 7-O-MA stimulated the reactivation of insulin-mediated phosphorylation of phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB) and adenosine 5'-monophosphate-activated protein kinase (AMPK) in high glucose-induced, insulin-resistant HepG2 cells, and this effect was blocked by either LY294002, a PI3K inhibitor, or compound C, an AMPK inhibitor.
682	20823563	Therefore, these results suggest that 7-O-MA might stimulate glucose uptake via PPARgamma2 activation and improve insulin resistance via PI3K and AMPK-dependent pathways, and be a potential candidate for the management of type 2 DM.
683	20842448	PRKAA2, the gene that encodes the α2 catalytic subunit of AMPK, showed be involved in the glucose and lipid metabolism.
684	20929977	Accordingly, the deacetylase SIRT1 and the kinase AMPK increase PGC-1α activity.
685	20929977	RESEARCH DESIGN AND METHODS We tested whether chronic treadmill exercise or a single exercise session modifies PGC-1α activation and mitochondrial biogenesis differentially in obese ob/ob mice with dysregulated adiponectin/leptin-mediated AMPK activation compared with C57BL/6J wild-type mice.
686	20929977	RESULTS Exercise training (12 weeks) induced adiponectin and lowered plasma insulin and glucose, suggesting improved insulin sensitivity in wild-type mice.
687	20929977	Parallel to this, we observed AMPK activation, PGC-1α deacetylation, and SIRT1 induction in trained wild-type mice.
688	20929977	Treatment of C2C12 myoblasts with leptin or adiponectin resulted in increased AMPK phosphorylation and PGC-1α deacetylation.
689	20929977	CONCLUSIONS Chronic exercise induces mitochondrial biogenesis in wild-type mice, which may require intact AMPK activation by adipocytokines and involve SIRT1-dependent PGC-1α deacetylation.
690	20929977	Trained ob/ob mice appear to have partially adapted to reduced mitochondrial biogenesis by AMPK/SIRT1/PGC-1α-independent mechanisms without mtDNA replication.
691	20929977	Accordingly, the deacetylase SIRT1 and the kinase AMPK increase PGC-1α activity.
692	20929977	RESEARCH DESIGN AND METHODS We tested whether chronic treadmill exercise or a single exercise session modifies PGC-1α activation and mitochondrial biogenesis differentially in obese ob/ob mice with dysregulated adiponectin/leptin-mediated AMPK activation compared with C57BL/6J wild-type mice.
693	20929977	RESULTS Exercise training (12 weeks) induced adiponectin and lowered plasma insulin and glucose, suggesting improved insulin sensitivity in wild-type mice.
694	20929977	Parallel to this, we observed AMPK activation, PGC-1α deacetylation, and SIRT1 induction in trained wild-type mice.
695	20929977	Treatment of C2C12 myoblasts with leptin or adiponectin resulted in increased AMPK phosphorylation and PGC-1α deacetylation.
696	20929977	CONCLUSIONS Chronic exercise induces mitochondrial biogenesis in wild-type mice, which may require intact AMPK activation by adipocytokines and involve SIRT1-dependent PGC-1α deacetylation.
697	20929977	Trained ob/ob mice appear to have partially adapted to reduced mitochondrial biogenesis by AMPK/SIRT1/PGC-1α-independent mechanisms without mtDNA replication.
698	20929977	Accordingly, the deacetylase SIRT1 and the kinase AMPK increase PGC-1α activity.
699	20929977	RESEARCH DESIGN AND METHODS We tested whether chronic treadmill exercise or a single exercise session modifies PGC-1α activation and mitochondrial biogenesis differentially in obese ob/ob mice with dysregulated adiponectin/leptin-mediated AMPK activation compared with C57BL/6J wild-type mice.
700	20929977	RESULTS Exercise training (12 weeks) induced adiponectin and lowered plasma insulin and glucose, suggesting improved insulin sensitivity in wild-type mice.
701	20929977	Parallel to this, we observed AMPK activation, PGC-1α deacetylation, and SIRT1 induction in trained wild-type mice.
702	20929977	Treatment of C2C12 myoblasts with leptin or adiponectin resulted in increased AMPK phosphorylation and PGC-1α deacetylation.
703	20929977	CONCLUSIONS Chronic exercise induces mitochondrial biogenesis in wild-type mice, which may require intact AMPK activation by adipocytokines and involve SIRT1-dependent PGC-1α deacetylation.
704	20929977	Trained ob/ob mice appear to have partially adapted to reduced mitochondrial biogenesis by AMPK/SIRT1/PGC-1α-independent mechanisms without mtDNA replication.
705	20929977	Accordingly, the deacetylase SIRT1 and the kinase AMPK increase PGC-1α activity.
706	20929977	RESEARCH DESIGN AND METHODS We tested whether chronic treadmill exercise or a single exercise session modifies PGC-1α activation and mitochondrial biogenesis differentially in obese ob/ob mice with dysregulated adiponectin/leptin-mediated AMPK activation compared with C57BL/6J wild-type mice.
707	20929977	RESULTS Exercise training (12 weeks) induced adiponectin and lowered plasma insulin and glucose, suggesting improved insulin sensitivity in wild-type mice.
708	20929977	Parallel to this, we observed AMPK activation, PGC-1α deacetylation, and SIRT1 induction in trained wild-type mice.
709	20929977	Treatment of C2C12 myoblasts with leptin or adiponectin resulted in increased AMPK phosphorylation and PGC-1α deacetylation.
710	20929977	CONCLUSIONS Chronic exercise induces mitochondrial biogenesis in wild-type mice, which may require intact AMPK activation by adipocytokines and involve SIRT1-dependent PGC-1α deacetylation.
711	20929977	Trained ob/ob mice appear to have partially adapted to reduced mitochondrial biogenesis by AMPK/SIRT1/PGC-1α-independent mechanisms without mtDNA replication.
712	20929977	Accordingly, the deacetylase SIRT1 and the kinase AMPK increase PGC-1α activity.
713	20929977	RESEARCH DESIGN AND METHODS We tested whether chronic treadmill exercise or a single exercise session modifies PGC-1α activation and mitochondrial biogenesis differentially in obese ob/ob mice with dysregulated adiponectin/leptin-mediated AMPK activation compared with C57BL/6J wild-type mice.
714	20929977	RESULTS Exercise training (12 weeks) induced adiponectin and lowered plasma insulin and glucose, suggesting improved insulin sensitivity in wild-type mice.
715	20929977	Parallel to this, we observed AMPK activation, PGC-1α deacetylation, and SIRT1 induction in trained wild-type mice.
716	20929977	Treatment of C2C12 myoblasts with leptin or adiponectin resulted in increased AMPK phosphorylation and PGC-1α deacetylation.
717	20929977	CONCLUSIONS Chronic exercise induces mitochondrial biogenesis in wild-type mice, which may require intact AMPK activation by adipocytokines and involve SIRT1-dependent PGC-1α deacetylation.
718	20929977	Trained ob/ob mice appear to have partially adapted to reduced mitochondrial biogenesis by AMPK/SIRT1/PGC-1α-independent mechanisms without mtDNA replication.
719	20929977	Accordingly, the deacetylase SIRT1 and the kinase AMPK increase PGC-1α activity.
720	20929977	RESEARCH DESIGN AND METHODS We tested whether chronic treadmill exercise or a single exercise session modifies PGC-1α activation and mitochondrial biogenesis differentially in obese ob/ob mice with dysregulated adiponectin/leptin-mediated AMPK activation compared with C57BL/6J wild-type mice.
721	20929977	RESULTS Exercise training (12 weeks) induced adiponectin and lowered plasma insulin and glucose, suggesting improved insulin sensitivity in wild-type mice.
722	20929977	Parallel to this, we observed AMPK activation, PGC-1α deacetylation, and SIRT1 induction in trained wild-type mice.
723	20929977	Treatment of C2C12 myoblasts with leptin or adiponectin resulted in increased AMPK phosphorylation and PGC-1α deacetylation.
724	20929977	CONCLUSIONS Chronic exercise induces mitochondrial biogenesis in wild-type mice, which may require intact AMPK activation by adipocytokines and involve SIRT1-dependent PGC-1α deacetylation.
725	20929977	Trained ob/ob mice appear to have partially adapted to reduced mitochondrial biogenesis by AMPK/SIRT1/PGC-1α-independent mechanisms without mtDNA replication.
726	21035759	A liver-derived secretory protein, selenoprotein P, causes insulin resistance.
727	21035759	Here, we demonstrate that selenoprotein P (SeP), a liver-derived secretory protein, causes insulin resistance.
728	21035759	Using serial analysis of gene expression (SAGE) and DNA chip methods, we found that hepatic SeP mRNA levels correlated with insulin resistance in humans.
729	21035759	Administration of purified SeP impaired insulin signaling and dysregulated glucose metabolism in both hepatocytes and myocytes.
730	21035759	Conversely, both genetic deletion and RNA interference-mediated knockdown of SeP improved systemic insulin sensitivity and glucose tolerance in mice.
731	21035759	The metabolic actions of SeP were mediated, at least partly, by inactivation of adenosine monophosphate-activated protein kinase (AMPK).
732	21035759	In summary, these results demonstrate a role of SeP in the regulation of glucose metabolism and insulin sensitivity and suggest that SeP may be a therapeutic target for type 2 diabetes.
733	21042876	Rapamycin enhanced the isoproterenol-stimulated phosphorylation of hormone sensitive lipase (HSL) on Ser-563 (a PKA site), but had no effect on the phosphorylation of HSL S565 (an AMPK site).
734	21098866	Furthermore, the effects of metformin on the release of IL-1β, IL-6, IL-10, TGF-β, NO, and ROS as well as on the expression of arginase I, iNOS, NF-κB p65 and PGC-1α were not AMPK-dependent, because pretreatment of LPS-activated microglia with compound C, a pharmacological inhibitor of AMPK, did not reverse the effect of metformin.
735	21147283	Metformin induces osteoblast differentiation via orphan nuclear receptor SHP-mediated transactivation of Runx2.
736	21147283	Metformin increased significantly the expression of the key osteogenic genes, such as alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP) as well as SHP.
737	21147283	Transient transfection assays were performed in MC3T3E1 cells to confirm the effects of metformin on SHP, OC and Runx2 promoter activities.
738	21147283	Metformin increased the transcription of the SHP and OC genes, and the metformin effect was inhibited by dominant negative form of AMPK (DN-AMPK) or compound C (an inhibitor of AMPK).
739	21147283	The adenoviral overexpression of SHP increased significantly the level of ALP staining and OC production.
740	21147283	However, metformin did not have any significant effect on osteogenic gene expression, ALP staining and activity, and OC production in SHP null (SHP-/-) primary calvarial cells.
741	21147283	Moreover, upstream stimulatory factor-1 (USF-1) specifically mediated metformin-induced SHP gene expression.
742	21147283	In addition, metformin-induced AMPK activation increased the level of Runx2 mRNA and protein.
743	21147283	However, USF-1 and SHP were not involved in metformin-induced Runx2 expression.
744	21147283	Transient transfection and chromatin immunoprecipitation assays confirmed that metformin-induced SHP interacts physically and forms a complex with Runx2 on the osteocalcin gene promoter in MC3T3E1 cells.
745	21147283	These results suggest that metformin may stimulate osteoblast differentiation through the transactivation of Runx2 via AMPK/USF-1/SHP regulatory cascade in mouse calvaria-derived cells.
746	21147283	Metformin induces osteoblast differentiation via orphan nuclear receptor SHP-mediated transactivation of Runx2.
747	21147283	Metformin increased significantly the expression of the key osteogenic genes, such as alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP) as well as SHP.
748	21147283	Transient transfection assays were performed in MC3T3E1 cells to confirm the effects of metformin on SHP, OC and Runx2 promoter activities.
749	21147283	Metformin increased the transcription of the SHP and OC genes, and the metformin effect was inhibited by dominant negative form of AMPK (DN-AMPK) or compound C (an inhibitor of AMPK).
750	21147283	The adenoviral overexpression of SHP increased significantly the level of ALP staining and OC production.
751	21147283	However, metformin did not have any significant effect on osteogenic gene expression, ALP staining and activity, and OC production in SHP null (SHP-/-) primary calvarial cells.
752	21147283	Moreover, upstream stimulatory factor-1 (USF-1) specifically mediated metformin-induced SHP gene expression.
753	21147283	In addition, metformin-induced AMPK activation increased the level of Runx2 mRNA and protein.
754	21147283	However, USF-1 and SHP were not involved in metformin-induced Runx2 expression.
755	21147283	Transient transfection and chromatin immunoprecipitation assays confirmed that metformin-induced SHP interacts physically and forms a complex with Runx2 on the osteocalcin gene promoter in MC3T3E1 cells.
756	21147283	These results suggest that metformin may stimulate osteoblast differentiation through the transactivation of Runx2 via AMPK/USF-1/SHP regulatory cascade in mouse calvaria-derived cells.
757	21147283	Metformin induces osteoblast differentiation via orphan nuclear receptor SHP-mediated transactivation of Runx2.
758	21147283	Metformin increased significantly the expression of the key osteogenic genes, such as alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP) as well as SHP.
759	21147283	Transient transfection assays were performed in MC3T3E1 cells to confirm the effects of metformin on SHP, OC and Runx2 promoter activities.
760	21147283	Metformin increased the transcription of the SHP and OC genes, and the metformin effect was inhibited by dominant negative form of AMPK (DN-AMPK) or compound C (an inhibitor of AMPK).
761	21147283	The adenoviral overexpression of SHP increased significantly the level of ALP staining and OC production.
762	21147283	However, metformin did not have any significant effect on osteogenic gene expression, ALP staining and activity, and OC production in SHP null (SHP-/-) primary calvarial cells.
763	21147283	Moreover, upstream stimulatory factor-1 (USF-1) specifically mediated metformin-induced SHP gene expression.
764	21147283	In addition, metformin-induced AMPK activation increased the level of Runx2 mRNA and protein.
765	21147283	However, USF-1 and SHP were not involved in metformin-induced Runx2 expression.
766	21147283	Transient transfection and chromatin immunoprecipitation assays confirmed that metformin-induced SHP interacts physically and forms a complex with Runx2 on the osteocalcin gene promoter in MC3T3E1 cells.
767	21147283	These results suggest that metformin may stimulate osteoblast differentiation through the transactivation of Runx2 via AMPK/USF-1/SHP regulatory cascade in mouse calvaria-derived cells.
768	21186369	The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity, decreases inflammation and promotes cell survival.
769	21186369	Here, we show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, AdipoR1 and AdipoR2, and enhances ceramide catabolism and formation of its antiapoptotic metabolite--sphingosine-1-phosphate (S1P)--independently of AMP-dependent kinase (AMPK).
770	21186369	Using models of inducible apoptosis in pancreatic beta cells and cardiomyocytes, we show that transgenic overproduction of adiponectin decreases caspase-8-mediated death, whereas genetic ablation of adiponectin enhances apoptosis in vivo through a sphingolipid-mediated pathway.
771	21282364	Leucine deprivation increases hepatic insulin sensitivity via GCN2/mTOR/S6K1 and AMPK pathways.
772	21295959	Lactoferrin has been associated with insulin sensitivity in vivo and in vitro studies.
773	21295959	The effects of lactoferrin on adipogenesis were studied through the expression of different adipogenic and inflammatory markers, AMPK activation and Retinoblastoma 1 (RB1) activity.
774	21295959	The response to insulin was evaluated through (Ser473)AKT phosphorylation.
775	21295959	In both subcutaneous and visceral preadipocytes, lactoferrin (1 and 10 μM) increased adipogenic gene expressions and protein levels (fatty acid synthase, PPARγ, FABP4, ADIPOQ, ACC and STAMP2) and decreased inflammatory markers (IL8, IL6 and MCP1) dose-dependently in parallel to increased insulin-induced (Ser473)AKT phosphorylation.
776	21295959	In addition to these adipogenic effects, lactoferrin decreased significantly AMPK activity (reducing (pThr172)AMPK and (pSer79)ACC) and RB1 activity (increasing the (pser807/811)RB1/RB1 ratio).
777	21295959	In conclusion, these results suggest that lactoferrin promotes adipogenesis in human adipocytes by enhancing insulin signaling and inhibiting RB1 and AMPK activities.
778	21295959	Lactoferrin has been associated with insulin sensitivity in vivo and in vitro studies.
779	21295959	The effects of lactoferrin on adipogenesis were studied through the expression of different adipogenic and inflammatory markers, AMPK activation and Retinoblastoma 1 (RB1) activity.
780	21295959	The response to insulin was evaluated through (Ser473)AKT phosphorylation.
781	21295959	In both subcutaneous and visceral preadipocytes, lactoferrin (1 and 10 μM) increased adipogenic gene expressions and protein levels (fatty acid synthase, PPARγ, FABP4, ADIPOQ, ACC and STAMP2) and decreased inflammatory markers (IL8, IL6 and MCP1) dose-dependently in parallel to increased insulin-induced (Ser473)AKT phosphorylation.
782	21295959	In addition to these adipogenic effects, lactoferrin decreased significantly AMPK activity (reducing (pThr172)AMPK and (pSer79)ACC) and RB1 activity (increasing the (pser807/811)RB1/RB1 ratio).
783	21295959	In conclusion, these results suggest that lactoferrin promotes adipogenesis in human adipocytes by enhancing insulin signaling and inhibiting RB1 and AMPK activities.
784	21295959	Lactoferrin has been associated with insulin sensitivity in vivo and in vitro studies.
785	21295959	The effects of lactoferrin on adipogenesis were studied through the expression of different adipogenic and inflammatory markers, AMPK activation and Retinoblastoma 1 (RB1) activity.
786	21295959	The response to insulin was evaluated through (Ser473)AKT phosphorylation.
787	21295959	In both subcutaneous and visceral preadipocytes, lactoferrin (1 and 10 μM) increased adipogenic gene expressions and protein levels (fatty acid synthase, PPARγ, FABP4, ADIPOQ, ACC and STAMP2) and decreased inflammatory markers (IL8, IL6 and MCP1) dose-dependently in parallel to increased insulin-induced (Ser473)AKT phosphorylation.
788	21295959	In addition to these adipogenic effects, lactoferrin decreased significantly AMPK activity (reducing (pThr172)AMPK and (pSer79)ACC) and RB1 activity (increasing the (pser807/811)RB1/RB1 ratio).
789	21295959	In conclusion, these results suggest that lactoferrin promotes adipogenesis in human adipocytes by enhancing insulin signaling and inhibiting RB1 and AMPK activities.
790	21301998	Several potential mechanisms have been suggested for the ability of metformin to suppress cancer growth in vitro and vivo: (1) activation of LKB1/AMPK pathway, (2) induction of cell cycle arrest and/or apoptosis, (3) inhibition of protein synthesis, (4) reduction in circulating insulin levels, (5) inhibition of the unfolded protein response (UPR), (6) activation of the immune system, and (7) eradication of cancer stem cells.
791	21304897	The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK) and improvement of insulin sensitivity.
792	21304897	Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in liver by BBR.
793	21304897	Activities of transcription factors including Forkhead transcription factor O1 (FoxO1), sterol regulatory element-binding protein 1c (SREBP1) and carbohydrate responsive element-binding protein (ChREBP) were decreased.
794	21321316	A ketogenic diet impairs energy and glucose homeostasis by the attenuation of hypothalamic leptin signaling and hepatic insulin signaling in a rat model of non-obese type 2 diabetes.
795	21321316	KTD, but not IHB, attenuated hypothalamic signal transducer and activator of transcription 3 and 5'-adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in KTD.
796	21321316	The increased hepatic glucose output in KTD was associated with increased hepatic phosphoenolpyruvate carboxykinase expression through attenuated tyrosine phosphorylation of IRS2 and phosphorylation of Akt(Ser473).
797	21321316	In conclusion, KTD impairs energy and glucose homeostasis by exacerbating insulin resistance and attenuating hypothalamic leptin signaling in non-obese type 2 diabetic rats.
798	21459325	Adiponectin enhances insulin sensitivity by increasing hepatic IRS-2 expression via a macrophage-derived IL-6-dependent pathway.
799	21459325	Many actions of adiponectin, a well-recognized antidiabetic adipokine, are currently attributed to the activation of two critical molecules downstream of AdipoR1 and R2: AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα).
800	21459325	However, the direct effects of adiponectin on insulin signaling molecules remain poorly understood.
801	21459325	We show here that adiponectin upregulates IRS-2 through activation of signal transducer and activator of transcription-3 (STAT3).
802	21459325	Surprisingly, this activation is associated with IL-6 production from macrophages induced by adiponectin through NFκB activation independent of its authentic receptors, AdipoR1 and AdipoR2.
803	21459325	These data have unraveled an insulin-sensitizing action initiated by adiponectin leading to upregulation of hepatic IRS-2 via an IL-6 dependent pathway through a still unidentified adiponectin receptor.
804	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.
805	21505148	Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation.
806	21505148	In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood.
807	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.
808	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).
809	21505148	Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700).
810	21505148	Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation.
811	21505148	These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.
812	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.
813	21505148	Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation.
814	21505148	In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood.
815	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.
816	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).
817	21505148	Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700).
818	21505148	Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation.
819	21505148	These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.
820	21584245	The In Vivo Antidiabetic Activity of Nigella sativa Is Mediated through Activation of the AMPK Pathway and Increased Muscle Glut4 Content.
821	21584245	Upon sacrifice, plasma lipid profile, insulin, leptin, and adiponectin levels were assessed.
822	21584245	Leptin and adiponectin were unchanged.
823	21584245	More significantly, our data demonstrate that in vivo treatment with NSE exerts an insulin-sensitizing action by enhancing ACC phosphorylation, a major component of the insulin-independent AMPK signaling pathway, and by enhancing muscle Glut4 expression.
824	21584245	The In Vivo Antidiabetic Activity of Nigella sativa Is Mediated through Activation of the AMPK Pathway and Increased Muscle Glut4 Content.
825	21584245	Upon sacrifice, plasma lipid profile, insulin, leptin, and adiponectin levels were assessed.
826	21584245	Leptin and adiponectin were unchanged.
827	21584245	More significantly, our data demonstrate that in vivo treatment with NSE exerts an insulin-sensitizing action by enhancing ACC phosphorylation, a major component of the insulin-independent AMPK signaling pathway, and by enhancing muscle Glut4 expression.
828	21606593	Furthermore, in primary mouse hepatocytes, the absence of LKB1, AMPK, or the transcriptional coactivator CRTC2 did not prevent adiponectin from inhibiting glucose output or reducing gluconeogenic gene expression.
829	21606593	These results reveal that whereas some of the hormone's actions in vivo may be LKB1 dependent, substantial LKB1-, AMPK-, and CRTC2-independent signaling pathways also mediate effects of adiponectin.
830	21606593	Furthermore, in primary mouse hepatocytes, the absence of LKB1, AMPK, or the transcriptional coactivator CRTC2 did not prevent adiponectin from inhibiting glucose output or reducing gluconeogenic gene expression.
831	21606593	These results reveal that whereas some of the hormone's actions in vivo may be LKB1 dependent, substantial LKB1-, AMPK-, and CRTC2-independent signaling pathways also mediate effects of adiponectin.
832	21613414	GLUT1 enhances mTOR activity independently of TSC2 and AMPK.
833	21613414	We found that levels of GLUT1 expression and mTOR activation, as evidenced by S6 kinase (S6K) and 4E-BP-1 phosphorylation, changed in tandem in cell lines exposed to elevated levels of extracellular glucose.
834	21613414	Conversely, enhanced GLUT1 expression led to a 2.4-fold increase in binding of mTOR to its activator, Rheb, and a commensurate 2.1-fold decrease in binding of Rheb to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) consistent with mediation of GLUT1 effects by a metabolic effect on GAPDH.
835	21613414	Thus, GLUT1 expression appears to augment mesangial cell growth and matrix protein accumulation via effects on glycolysis and decreased GAPDH interaction with Rheb.
836	21700896	Reductions in RIP140 are not required for exercise- and AICAR-mediated increases in skeletal muscle mitochondrial content.
837	21700896	Since β-GPA feeding reduces high-energy phosphate levels and activates AMPK, alterations reminiscent of exercise, we hypothesized that exercise training would reduce RIP140 protein content.
838	21700896	We found that 6 wk of daily 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) injections had no effect on RIP140 protein content in rat skeletal muscle while RIP140 content from LKB1 knockout mice was unaltered despite reductions in mitochondria.
839	21700896	An acute bout of exercise, AICAR treatment, and epinephrine injections increased the mRNA levels of PGC-1α, COXIV, and lipin1 independent of decreases in nuclear RIP140 protein.
840	21700896	In conclusion our results demonstrate that decreases in RIP140 protein content are not required for exercise and AMPK-dependent increases in skeletal muscle mitochondrial content, nor do acute perturbations alter the cellular localization of RIP140 in parallel with the induction of genes involved in mitochondrial biogenesis.
841	21700896	Reductions in RIP140 are not required for exercise- and AICAR-mediated increases in skeletal muscle mitochondrial content.
842	21700896	Since β-GPA feeding reduces high-energy phosphate levels and activates AMPK, alterations reminiscent of exercise, we hypothesized that exercise training would reduce RIP140 protein content.
843	21700896	We found that 6 wk of daily 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) injections had no effect on RIP140 protein content in rat skeletal muscle while RIP140 content from LKB1 knockout mice was unaltered despite reductions in mitochondria.
844	21700896	An acute bout of exercise, AICAR treatment, and epinephrine injections increased the mRNA levels of PGC-1α, COXIV, and lipin1 independent of decreases in nuclear RIP140 protein.
845	21700896	In conclusion our results demonstrate that decreases in RIP140 protein content are not required for exercise and AMPK-dependent increases in skeletal muscle mitochondrial content, nor do acute perturbations alter the cellular localization of RIP140 in parallel with the induction of genes involved in mitochondrial biogenesis.
846	21723508	Mechanistically, adiponectin activates AMPK/eNOS and cAMP/PKA signaling pathways in aortae, which increase NO bioavailability and reduce oxidative stress.
847	21742060	In neurons, the nutrient excess associated with prolonged diabetes may trigger a switching off of AMP kinase (AMPK) and/or silent information regulator T1 (SIRT1) signaling leading to impaired peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α) expression/activity and diminished mitochondrial activity.
848	21779523	Exercise training (ET) and selenium (SEL) were evaluated either individually or in combination (COMBI) for their effects on expression of glucose (AMPK, PGC-1α, GLUT-4) and lactate metabolic proteins (LDH, MCT-1, MCT-4, COX-IV) in heart and skeletal muscles in a rodent model (Goto-Kakisaki, GK) of diabetes.
849	21779523	In particular, ET alone, SEL alone, or COMBI induced upregulation of glucose (AMPK, PGC-1α, GLUT-4) and lactate (LDH, MCT-1, MCT-4, COX-IV) metabolic proteins relative to SED.
850	21779523	Exercise training (ET) and selenium (SEL) were evaluated either individually or in combination (COMBI) for their effects on expression of glucose (AMPK, PGC-1α, GLUT-4) and lactate metabolic proteins (LDH, MCT-1, MCT-4, COX-IV) in heart and skeletal muscles in a rodent model (Goto-Kakisaki, GK) of diabetes.
851	21779523	In particular, ET alone, SEL alone, or COMBI induced upregulation of glucose (AMPK, PGC-1α, GLUT-4) and lactate (LDH, MCT-1, MCT-4, COX-IV) metabolic proteins relative to SED.
852	21857156	Moreover, leptin stimulated canonical autophagy in cultured human or mouse cell lines, a phenomenon that was coupled to the activation of adenosine monophosphate-dependent kianse (AMPK), as well as the inhibition of mammalian target of rapamycin (mTOR), and that was confirmed by autophagic flux measurements.
853	21907197	Resveratrol may exert these effects by targeting several key metabolic sensor/effector proteins, such as AMPK, SIRT1, and PGC-1α.
854	21907197	Resveratrol has also received considerable attention recently for its potential neuroprotective effects in neurodegenerative disorders where AMPK, SIRT1 or PGC-1α may represent promising therapeutic targets.
855	21907197	Resveratrol may exert these effects by targeting several key metabolic sensor/effector proteins, such as AMPK, SIRT1, and PGC-1α.
856	21907197	Resveratrol has also received considerable attention recently for its potential neuroprotective effects in neurodegenerative disorders where AMPK, SIRT1 or PGC-1α may represent promising therapeutic targets.
857	21945951	The activation of the p53 pathway by the AMP mimetic AICAR is reduced by inhibitors of the ATM or mTOR kinases.
858	21945951	A reduced supply of energy at the cellular level leads to an increased concentration of AMP, which, in turn, results in LKB1-mediated activation of the AMPK kinase.
859	21945951	The activation of the p53 tumor suppressor protein by metabolic stress has been shown to be mediated by AMPK.
860	21945951	We showed that AICAR activated the p53 pathway in LKB1-deficient cells.
861	21945951	In cells with ATM expression silenced by shRNA, AICAR-induced p53 phosphorylation at Ser(15) and Ser(37) was attenuated.
862	21945951	Furthermore, p53 activation by AICAR was blocked by rapamycin, a specific inhibitor of the mTOR kinase, which is a crucial regulator of cell growth.
863	21945951	Rapamycin did not block p53 activation by resveratrol, which, in contrast to AICAR, induced the DNA damage response, senescence-like growth inhibition, a high level of post-translational modification of p53, and weak upregulation of MDM2 (the negative regulator of p53).
864	21945951	Thus, ATM and mTOR participate in the activation of p53 in response to a compound mimicking metabolic stress.
865	21945951	The activation of the p53 pathway by the AMP mimetic AICAR is reduced by inhibitors of the ATM or mTOR kinases.
866	21945951	A reduced supply of energy at the cellular level leads to an increased concentration of AMP, which, in turn, results in LKB1-mediated activation of the AMPK kinase.
867	21945951	The activation of the p53 tumor suppressor protein by metabolic stress has been shown to be mediated by AMPK.
868	21945951	We showed that AICAR activated the p53 pathway in LKB1-deficient cells.
869	21945951	In cells with ATM expression silenced by shRNA, AICAR-induced p53 phosphorylation at Ser(15) and Ser(37) was attenuated.
870	21945951	Furthermore, p53 activation by AICAR was blocked by rapamycin, a specific inhibitor of the mTOR kinase, which is a crucial regulator of cell growth.
871	21945951	Rapamycin did not block p53 activation by resveratrol, which, in contrast to AICAR, induced the DNA damage response, senescence-like growth inhibition, a high level of post-translational modification of p53, and weak upregulation of MDM2 (the negative regulator of p53).
872	21945951	Thus, ATM and mTOR participate in the activation of p53 in response to a compound mimicking metabolic stress.
873	22050309	Adiponectin improves insulin sensitivity, promotes vascular health, and increases cell survival.
874	22050309	Two receptors for adiponectin (ADIPOR1 and ADIPOR2) have been cloned, and activation of adenosine monophosphate-activated kinase (AMPK) has been reported to be downstream of the receptors.
875	22050309	Interestingly, a new report also identified a pathway involving adiponectin and insulin receptor substrate 2, which is independent of the ADIPOR1/ADIPOR2 pathway.
876	22068602	Altered REDD1, myostatin, and Akt/mTOR/FoxO/MAPK signaling in streptozotocin-induced diabetic muscle atrophy.
877	22068602	Concomitantly, increased phosphorylation of AMPK and dephosphorylation of the Akt/mTOR/S6K1/FoxO pathway of proteins were observed together with increased protein ubiquitination.
878	22068602	Diabetes also induced an increase in myostatin protein and decreased MAPK signaling.
879	22068602	Of those, increased REDD1 and myostatin together with decreased Akt/mTOR/FoxO signaling are associated with diabetic muscle atrophy.
880	22068602	The increased REDD1 and decreased Akt/mTOR/FoxO signaling followed a similar time course and thus may be explained, in part, by increased expression of genes in DNA damage/repair and possibly also decrease in ATP-production pathways.
881	22323564	Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue.
882	22323564	We previously reported that adenosine monophosphate-activated protein kinase (AMPK) activity is lower in adipose tissue of morbidly obese individuals who are insulin resistant than in comparably obese people who are insulin sensitive.
883	22323564	We confirmed that AMPK activity is diminished in the insulin resistant group.
884	22323564	A custom PCR array revealed increases in mRNA levels of a wide variety of genes associated with inflammation and decreases in PGC-1α and Nampt in omental fat of the insulin resistant group.
885	22323564	In contrast, subcutaneous abdominal fat of the same patients showed increases in PTP-1b, VEGFa, IFNγ, PAI-1, and NOS-2 not observed in omental fat.
886	22323564	Only angiotensinogen and CD4(+) mRNA levels were increased in both depots.
887	22323564	Thus, adipose tissues of markedly obese insulin resistant individuals uniformly show decreased AMPK activity and increased oxidative stress compared with insulin sensitive patients.
888	22323564	Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue.
889	22323564	We previously reported that adenosine monophosphate-activated protein kinase (AMPK) activity is lower in adipose tissue of morbidly obese individuals who are insulin resistant than in comparably obese people who are insulin sensitive.
890	22323564	We confirmed that AMPK activity is diminished in the insulin resistant group.
891	22323564	A custom PCR array revealed increases in mRNA levels of a wide variety of genes associated with inflammation and decreases in PGC-1α and Nampt in omental fat of the insulin resistant group.
892	22323564	In contrast, subcutaneous abdominal fat of the same patients showed increases in PTP-1b, VEGFa, IFNγ, PAI-1, and NOS-2 not observed in omental fat.
893	22323564	Only angiotensinogen and CD4(+) mRNA levels were increased in both depots.
894	22323564	Thus, adipose tissues of markedly obese insulin resistant individuals uniformly show decreased AMPK activity and increased oxidative stress compared with insulin sensitive patients.
895	22323564	Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue.
896	22323564	We previously reported that adenosine monophosphate-activated protein kinase (AMPK) activity is lower in adipose tissue of morbidly obese individuals who are insulin resistant than in comparably obese people who are insulin sensitive.
897	22323564	We confirmed that AMPK activity is diminished in the insulin resistant group.
898	22323564	A custom PCR array revealed increases in mRNA levels of a wide variety of genes associated with inflammation and decreases in PGC-1α and Nampt in omental fat of the insulin resistant group.
899	22323564	In contrast, subcutaneous abdominal fat of the same patients showed increases in PTP-1b, VEGFa, IFNγ, PAI-1, and NOS-2 not observed in omental fat.
900	22323564	Only angiotensinogen and CD4(+) mRNA levels were increased in both depots.
901	22323564	Thus, adipose tissues of markedly obese insulin resistant individuals uniformly show decreased AMPK activity and increased oxidative stress compared with insulin sensitive patients.
902	22323564	Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue.
903	22323564	We previously reported that adenosine monophosphate-activated protein kinase (AMPK) activity is lower in adipose tissue of morbidly obese individuals who are insulin resistant than in comparably obese people who are insulin sensitive.
904	22323564	We confirmed that AMPK activity is diminished in the insulin resistant group.
905	22323564	A custom PCR array revealed increases in mRNA levels of a wide variety of genes associated with inflammation and decreases in PGC-1α and Nampt in omental fat of the insulin resistant group.
906	22323564	In contrast, subcutaneous abdominal fat of the same patients showed increases in PTP-1b, VEGFa, IFNγ, PAI-1, and NOS-2 not observed in omental fat.
907	22323564	Only angiotensinogen and CD4(+) mRNA levels were increased in both depots.
908	22323564	Thus, adipose tissues of markedly obese insulin resistant individuals uniformly show decreased AMPK activity and increased oxidative stress compared with insulin sensitive patients.
909	22349765	The changes in AMPK-α protein content significantly related (p < 0.001) to the changes in GLUT-4 translocation (r = 0.78) and Hb1Ac levels (r = -0.68), suggesting that AMPK signaling may be implicated in the effects of supplementation on glucose uptake in type 2 diabetes.
910	22389706	Absence of RIP140 reveals a pathway regulating glut4-dependent glucose uptake in oxidative skeletal muscle through UCP1-mediated activation of AMPK.
911	22389706	In the RIP140-null soleus, depletion of RIP140 leads to increased GLUT4 trafficking and glucose uptake with no change in Akt activity.
912	22389706	AMPK phosphorylation/activity is inhibited in the soleus of RIP140 transgenic mice and increased in RIP140-null soleus.
913	22389706	This is associated with increased UCP1 expression and mitochondrial uncoupling revealing the existence of a signaling pathway controlling insulin-independent glucose uptake in the soleus of RIP140-null mice.
914	22389706	In conclusion, our findings reinforce the participation of RIP140 in the maintenance of energy homeostasis by acting as an inhibitor of energy production and particularly point to RIP140 as a promising therapeutic target in the treatment of insulin resistance.
915	22389706	Absence of RIP140 reveals a pathway regulating glut4-dependent glucose uptake in oxidative skeletal muscle through UCP1-mediated activation of AMPK.
916	22389706	In the RIP140-null soleus, depletion of RIP140 leads to increased GLUT4 trafficking and glucose uptake with no change in Akt activity.
917	22389706	AMPK phosphorylation/activity is inhibited in the soleus of RIP140 transgenic mice and increased in RIP140-null soleus.
918	22389706	This is associated with increased UCP1 expression and mitochondrial uncoupling revealing the existence of a signaling pathway controlling insulin-independent glucose uptake in the soleus of RIP140-null mice.
919	22389706	In conclusion, our findings reinforce the participation of RIP140 in the maintenance of energy homeostasis by acting as an inhibitor of energy production and particularly point to RIP140 as a promising therapeutic target in the treatment of insulin resistance.
920	22412912	GLUT 4 translocation, phosphorylation of AMPK and Akt, AMPK activity, and association of IRS-1 and PI3K were investigated in the presence of CGA.
921	22412912	Consistent with these results, CGA was found to phosphorylate AMPK and ACC, consistent with the result of increased AMPK activities.
922	22412912	CGA did not appear to enhance association of IRS-1 with p85.
923	22412912	GLUT 4 translocation, phosphorylation of AMPK and Akt, AMPK activity, and association of IRS-1 and PI3K were investigated in the presence of CGA.
924	22412912	Consistent with these results, CGA was found to phosphorylate AMPK and ACC, consistent with the result of increased AMPK activities.
925	22412912	CGA did not appear to enhance association of IRS-1 with p85.
926	22450341	Adiponectin is a white and brown adipose tissue hormone, also known as gelatin-binding protein-28 (GBP28), AdipoQ, adipocyte complement-related protein (ACRP30), or apM1.
927	22450341	Adiponectin is an insulin sensitizing hormone that exerts its action through its receptors AdipoR1, AdipoR2, and T-cadherin.
928	22450341	AdipoR1 is expressed abundantly in muscle, whereas AdipoR2 is predominantly expressed in the liver.
929	22450341	Adiponectin is inversely proportional to obesity, diabetes, and other insulin-resistant states.
930	22450341	Adiponectin enhances AMPK and the PPARα pathway in the liver and skeletal muscle.
931	22450341	Adiponectin increases fatty acids oxidation, which lowers circulating free fatty acids and prevents insulin resistance.
932	22450341	Apart from causing metabolic dysfunction, adiponectin deficiency may also contribute to coronary heart disease, steatohepatitis, insulin resistance, nonalcoholic fatty liver disease, and a wide array of cancers.
933	22492282	Plasma adiponectin and adiponectin receptor (AdipoR1) in muscle are down-regulated in obesity.
934	22492282	Analysis of muscle-specific AdipoR1 knockout mice revealed the pivotal role of adiponectin/AdipoR1 in the regulation of mitochondrial biogenesis via AMPK- and SIRT1-mediated PGC-1α activation as well as Ca(2+)-dependent up-regulation of PGC-1α expression.
935	22492282	Reduced adiponectin/AdipoR1 signals in muscle in obesity appear to cause PGC-1α inactivation as well as down-regulation and consequently impaired mitochondrial biogenesis and insulin resistance.
936	22492282	Computational motif analyses of adipocyte-specific FAIRE peaks confirmed PPARγ and CCAAT-enhancer binding proteins (C/EBPs) on the top list, consistent with their crucial roles in adipogenic transcription, and also revealed NFIA and NFIB to be important regulators of proper adipocyte differentiation.
937	22561086	Moreover, we show that the effect of metformin on Txnip gene transcription is due to the inhibition of mitochondrial complex I and increased glycolysis, and is partially mediated by the AMP activated kinase (AMPK).
938	22571857	The fuel switch to fatty acid oxidation depends on the sensing of AMP and NAD(+) by AMPK and the SirT family of deacetylases (e.g., SirT1, -6, and -3), respectively, which couple inflammation and metabolism by chromatin and protein reprogramming.
939	22579688	In muscle cells, 5' adenosine monophosphate-activated protein kinase (AMPK) is known as another GLUT4 translocation promoter.
940	22579688	Natural compounds that activate AMPK have a possibility to overcome insulin resistance in the diabetic state.
941	22579688	In this study, we investigate the in vitro effect of piceatannol on glucose uptake, AMPK phosphorylation and GLUT4 translocation to plasma membrane in L6 myocytes, and its in vivo effect on blood glucose levels in type 2 diabetic model db/db mice.
942	22579688	Piceatannol was found to promote glucose uptake, AMPK phosphorylation and GLUT4 translocation by Western blotting analyses in L6 myotubes under a condition of insulin absence.
943	22579688	In muscle cells, 5' adenosine monophosphate-activated protein kinase (AMPK) is known as another GLUT4 translocation promoter.
944	22579688	Natural compounds that activate AMPK have a possibility to overcome insulin resistance in the diabetic state.
945	22579688	In this study, we investigate the in vitro effect of piceatannol on glucose uptake, AMPK phosphorylation and GLUT4 translocation to plasma membrane in L6 myocytes, and its in vivo effect on blood glucose levels in type 2 diabetic model db/db mice.
946	22579688	Piceatannol was found to promote glucose uptake, AMPK phosphorylation and GLUT4 translocation by Western blotting analyses in L6 myotubes under a condition of insulin absence.
947	22579688	In muscle cells, 5' adenosine monophosphate-activated protein kinase (AMPK) is known as another GLUT4 translocation promoter.
948	22579688	Natural compounds that activate AMPK have a possibility to overcome insulin resistance in the diabetic state.
949	22579688	In this study, we investigate the in vitro effect of piceatannol on glucose uptake, AMPK phosphorylation and GLUT4 translocation to plasma membrane in L6 myocytes, and its in vivo effect on blood glucose levels in type 2 diabetic model db/db mice.
950	22579688	Piceatannol was found to promote glucose uptake, AMPK phosphorylation and GLUT4 translocation by Western blotting analyses in L6 myotubes under a condition of insulin absence.
951	22579688	In muscle cells, 5' adenosine monophosphate-activated protein kinase (AMPK) is known as another GLUT4 translocation promoter.
952	22579688	Natural compounds that activate AMPK have a possibility to overcome insulin resistance in the diabetic state.
953	22579688	In this study, we investigate the in vitro effect of piceatannol on glucose uptake, AMPK phosphorylation and GLUT4 translocation to plasma membrane in L6 myocytes, and its in vivo effect on blood glucose levels in type 2 diabetic model db/db mice.
954	22579688	Piceatannol was found to promote glucose uptake, AMPK phosphorylation and GLUT4 translocation by Western blotting analyses in L6 myotubes under a condition of insulin absence.
955	22664981	Effects of lipoic acid on AMPK and adiponectin in adipose tissue of low- and high-fat-fed rats.
956	22674476	Effect of dietary macronutrient composition on AMPK and SIRT1 expression and activity in human skeletal muscle.
957	22674476	Adenosine monophosphate-activated protein kinase (AMPK), silent mating type information regulation 2 homologue 1 (SIRT 1), and peroxisome proliferator-activated receptor γ co-activator α (PGC1α) constitute an energy sensing cellular network that controls mitochondrial biogenesis.
958	22674476	Caloric restriction activates both AMPK and SIRT-1 to increase ATP production from fat oxidation.
959	22674476	AMPK phosphorylation and acetylation of PGC1α (as a measure of SIRT activity) were determined.
960	22674476	Under both conditions - overfeeding and caloric restriction - high fat/low carbohydrate (HF/LC) diet significantly increased phosphorylation of AMPK and deacetylation of PGC1α in skeletal muscle without affecting total amounts of AMPK, PGC1α, or SIRT 1.
961	22674476	Effect of dietary macronutrient composition on AMPK and SIRT1 expression and activity in human skeletal muscle.
962	22674476	Adenosine monophosphate-activated protein kinase (AMPK), silent mating type information regulation 2 homologue 1 (SIRT 1), and peroxisome proliferator-activated receptor γ co-activator α (PGC1α) constitute an energy sensing cellular network that controls mitochondrial biogenesis.
963	22674476	Caloric restriction activates both AMPK and SIRT-1 to increase ATP production from fat oxidation.
964	22674476	AMPK phosphorylation and acetylation of PGC1α (as a measure of SIRT activity) were determined.
965	22674476	Under both conditions - overfeeding and caloric restriction - high fat/low carbohydrate (HF/LC) diet significantly increased phosphorylation of AMPK and deacetylation of PGC1α in skeletal muscle without affecting total amounts of AMPK, PGC1α, or SIRT 1.
966	22674476	Effect of dietary macronutrient composition on AMPK and SIRT1 expression and activity in human skeletal muscle.
967	22674476	Adenosine monophosphate-activated protein kinase (AMPK), silent mating type information regulation 2 homologue 1 (SIRT 1), and peroxisome proliferator-activated receptor γ co-activator α (PGC1α) constitute an energy sensing cellular network that controls mitochondrial biogenesis.
968	22674476	Caloric restriction activates both AMPK and SIRT-1 to increase ATP production from fat oxidation.
969	22674476	AMPK phosphorylation and acetylation of PGC1α (as a measure of SIRT activity) were determined.
970	22674476	Under both conditions - overfeeding and caloric restriction - high fat/low carbohydrate (HF/LC) diet significantly increased phosphorylation of AMPK and deacetylation of PGC1α in skeletal muscle without affecting total amounts of AMPK, PGC1α, or SIRT 1.
971	22674476	Effect of dietary macronutrient composition on AMPK and SIRT1 expression and activity in human skeletal muscle.
972	22674476	Adenosine monophosphate-activated protein kinase (AMPK), silent mating type information regulation 2 homologue 1 (SIRT 1), and peroxisome proliferator-activated receptor γ co-activator α (PGC1α) constitute an energy sensing cellular network that controls mitochondrial biogenesis.
973	22674476	Caloric restriction activates both AMPK and SIRT-1 to increase ATP production from fat oxidation.
974	22674476	AMPK phosphorylation and acetylation of PGC1α (as a measure of SIRT activity) were determined.
975	22674476	Under both conditions - overfeeding and caloric restriction - high fat/low carbohydrate (HF/LC) diet significantly increased phosphorylation of AMPK and deacetylation of PGC1α in skeletal muscle without affecting total amounts of AMPK, PGC1α, or SIRT 1.
976	22674476	Effect of dietary macronutrient composition on AMPK and SIRT1 expression and activity in human skeletal muscle.
977	22674476	Adenosine monophosphate-activated protein kinase (AMPK), silent mating type information regulation 2 homologue 1 (SIRT 1), and peroxisome proliferator-activated receptor γ co-activator α (PGC1α) constitute an energy sensing cellular network that controls mitochondrial biogenesis.
978	22674476	Caloric restriction activates both AMPK and SIRT-1 to increase ATP production from fat oxidation.
979	22674476	AMPK phosphorylation and acetylation of PGC1α (as a measure of SIRT activity) were determined.
980	22674476	Under both conditions - overfeeding and caloric restriction - high fat/low carbohydrate (HF/LC) diet significantly increased phosphorylation of AMPK and deacetylation of PGC1α in skeletal muscle without affecting total amounts of AMPK, PGC1α, or SIRT 1.
981	22675305	CoPP increased adiponectin levels and phosphorylation of AKT and AMPK and reversed the eNOS/iNOS expression imbalance observed in the untreated diabetic heart.
982	22675305	In this experimental model of diabetic cardiomyopathy, CoPP treatment improved both cardiac function and coronary flow by blunting oxidative stress, restoring eNOS/iNOS expression balance and increasing HO-1 levels, thereby favoring improvement in both endothelial function and insulin sensitivity.
983	22688332	Nesfatin-1 action in the brain increases insulin sensitivity through Akt/AMPK/TORC2 pathway in diet-induced insulin resistance.
984	22688332	In addition, central nesfatin-1 increased insulin receptor (InsR)/insulin receptor substrate-1 (IRS-1)/AMP-dependent protein kinase (AMPK)/Akt kinase (Akt)/target of rapamycin complex (TORC) 2 phosphorylation and resulted in an increase in Fos immunoreactivity in the hypothalamic nuclei that mediate glucose homeostasis.
985	22688332	Taken together, these results reveal what we believe to be a novel site of action of nesfatin-1 on HGP and the PEPCK/InsR/IRS-1/AMPK/Akt/TORC2 pathway and suggest that hypothalamic nesfatin-1 action through a neural-mediated pathway can contribute to increased peripheral and hepatic insulin sensitivity by decreasing gluconeogenesis and promoting peripheral glucose uptake in vivo.
986	22688332	Nesfatin-1 action in the brain increases insulin sensitivity through Akt/AMPK/TORC2 pathway in diet-induced insulin resistance.
987	22688332	In addition, central nesfatin-1 increased insulin receptor (InsR)/insulin receptor substrate-1 (IRS-1)/AMP-dependent protein kinase (AMPK)/Akt kinase (Akt)/target of rapamycin complex (TORC) 2 phosphorylation and resulted in an increase in Fos immunoreactivity in the hypothalamic nuclei that mediate glucose homeostasis.
988	22688332	Taken together, these results reveal what we believe to be a novel site of action of nesfatin-1 on HGP and the PEPCK/InsR/IRS-1/AMPK/Akt/TORC2 pathway and suggest that hypothalamic nesfatin-1 action through a neural-mediated pathway can contribute to increased peripheral and hepatic insulin sensitivity by decreasing gluconeogenesis and promoting peripheral glucose uptake in vivo.
989	22688332	Nesfatin-1 action in the brain increases insulin sensitivity through Akt/AMPK/TORC2 pathway in diet-induced insulin resistance.
990	22688332	In addition, central nesfatin-1 increased insulin receptor (InsR)/insulin receptor substrate-1 (IRS-1)/AMP-dependent protein kinase (AMPK)/Akt kinase (Akt)/target of rapamycin complex (TORC) 2 phosphorylation and resulted in an increase in Fos immunoreactivity in the hypothalamic nuclei that mediate glucose homeostasis.
991	22688332	Taken together, these results reveal what we believe to be a novel site of action of nesfatin-1 on HGP and the PEPCK/InsR/IRS-1/AMPK/Akt/TORC2 pathway and suggest that hypothalamic nesfatin-1 action through a neural-mediated pathway can contribute to increased peripheral and hepatic insulin sensitivity by decreasing gluconeogenesis and promoting peripheral glucose uptake in vivo.
992	22819702	Western blotting and semiquantitative RT-PCR analysis were used to assess adiponectin, Sirt1, and AMPK levels.
993	22819702	Telmisartan increased expression of Sirt1 mRNA and Sirt1 protein as well as the phosphorylation of AMPK in 3T3-L1 cells.
994	22819702	Telmisartan can increase adiponectin production in white adipose tissue partly via a PPAR-γ2-independent mechanism.
995	22819702	Western blotting and semiquantitative RT-PCR analysis were used to assess adiponectin, Sirt1, and AMPK levels.
996	22819702	Telmisartan increased expression of Sirt1 mRNA and Sirt1 protein as well as the phosphorylation of AMPK in 3T3-L1 cells.
997	22819702	Telmisartan can increase adiponectin production in white adipose tissue partly via a PPAR-γ2-independent mechanism.
998	22869320	Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2.
999	22869320	The insulin receptor substrate proteins IRS1 and IRS2 are key targets of the insulin receptor tyrosine kinase and are required for hormonal control of metabolism.
1000	22869320	However, IRS1 and IRS2 are regulated through a complex mechanism involving phosphorylation of >50 serine/threonine residues (S/T) within their long, unstructured tail regions.
1001	22869320	In cultured cells, insulin-stimulated kinases (including atypical PKC, AKT, SIK2, mTOR, S6K1, ERK1/2 and ROCK1) mediate feedback (autologous) S/T phosphorylation of IRS, with both positive and negative effects on insulin sensitivity.
1002	22869320	Additionally, insulin-independent (heterologous) kinases can phosphorylate IRS1/2 under basal conditions (AMPK, GSK3) or in response to sympathetic activation and lipid/inflammatory mediators, which are present at elevated levels in metabolic disease (GRK2, novel and conventional PKCs, JNK, IKKβ, mPLK).
1003	22916045	Dietary Aloe QDM complex lowered body weight, fasting blood glucose, plasma insulin, and leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice.
1004	22916045	Also, Aloe QDM complex significantly enhanced plasma adiponectin levels and insulin sensitivity via AMPK activity in muscles.
1005	22916045	Dietary Aloe QDM complex reduces obesity-induced glucose tolerance not only by suppressing PPARγ/LXRα but also by enhancing AMPK activity in the WAT and muscles, both of which are important peripheral tissues affecting insulin resistance.
1006	22916045	Dietary Aloe QDM complex lowered body weight, fasting blood glucose, plasma insulin, and leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice.
1007	22916045	Also, Aloe QDM complex significantly enhanced plasma adiponectin levels and insulin sensitivity via AMPK activity in muscles.
1008	22916045	Dietary Aloe QDM complex reduces obesity-induced glucose tolerance not only by suppressing PPARγ/LXRα but also by enhancing AMPK activity in the WAT and muscles, both of which are important peripheral tissues affecting insulin resistance.
1009	23118742	Metabolic status plays an important role in the regulation of FGF21, and we therefore examined whether metformin, an indirect AMPK-activator, regulates FGF21 expression in hepatocytes.
1010	23118742	To study the role of AMPK in the putative regulation of FGF21, hepatocytes were incubated with Compound C (an AMPK inhibitor) in the presence of metformin.
1011	23118742	The study shows that metformin is a potent inducer of hepatic FGF21 expression and that the effect of metformin seems to be mediated through AMPK activation.
1012	23118742	Metabolic status plays an important role in the regulation of FGF21, and we therefore examined whether metformin, an indirect AMPK-activator, regulates FGF21 expression in hepatocytes.
1013	23118742	To study the role of AMPK in the putative regulation of FGF21, hepatocytes were incubated with Compound C (an AMPK inhibitor) in the presence of metformin.
1014	23118742	The study shows that metformin is a potent inducer of hepatic FGF21 expression and that the effect of metformin seems to be mediated through AMPK activation.
1015	23118742	Metabolic status plays an important role in the regulation of FGF21, and we therefore examined whether metformin, an indirect AMPK-activator, regulates FGF21 expression in hepatocytes.
1016	23118742	To study the role of AMPK in the putative regulation of FGF21, hepatocytes were incubated with Compound C (an AMPK inhibitor) in the presence of metformin.
1017	23118742	The study shows that metformin is a potent inducer of hepatic FGF21 expression and that the effect of metformin seems to be mediated through AMPK activation.
1018	23162655	The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase.
1019	23162655	In leptin-treated cells, the drug reversed the effects of the cytokine on the AMPK and STAT3 pathways, but modulated Akt activity in a cell-dependent manner.
1020	23162655	Our results suggest that metformin or similar AMPK-targeting agents with optimized blood-brain-barrier penetrability could be developed as potential treatments of GBM and could be used in conjunction with other target drugs such as leptin receptor antagonists.
1021	23162655	The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase.
1022	23162655	In leptin-treated cells, the drug reversed the effects of the cytokine on the AMPK and STAT3 pathways, but modulated Akt activity in a cell-dependent manner.
1023	23162655	Our results suggest that metformin or similar AMPK-targeting agents with optimized blood-brain-barrier penetrability could be developed as potential treatments of GBM and could be used in conjunction with other target drugs such as leptin receptor antagonists.
1024	23162655	The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase.
1025	23162655	In leptin-treated cells, the drug reversed the effects of the cytokine on the AMPK and STAT3 pathways, but modulated Akt activity in a cell-dependent manner.
1026	23162655	Our results suggest that metformin or similar AMPK-targeting agents with optimized blood-brain-barrier penetrability could be developed as potential treatments of GBM and could be used in conjunction with other target drugs such as leptin receptor antagonists.
1027	23224631	Amylin-induced downregulation of hippocampal neurogenesis is attenuated by leptin in a STAT3/AMPK/ERK-dependent manner in mice.
1028	23261675	Furthermore, reduced thiobarbituric acid reactive substraces (TBARS), as well as increased activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px) in liver tissues were observed in the dieckol administered group.
1029	23261675	In addition, increased levels of the phosphorylation of AMPK and Akt were observed in the muscle tissues of the dieckol administered group in a Western blotting analysis.
1030	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).
1031	23428406	F015 significantly increased the phosphorylation of AKT, AS160 and ERK1/2, account for the augmented glucose transport capacity in L6 myotubes.
1032	23456781	Cocoa flavonoids improve insulin signalling and modulate glucose production via AKT and AMPK in HepG2 cells.
1033	23460046	Impaired mitochondrial biogenesis due to dysfunctional adiponectin-AMPK-PGC-1α signaling contributing to increased vulnerability in diabetic heart.
1034	23460046	Whether adiponectin (APN), a potent cardioprotective molecule, regulates cardiac mitochondrial function has also not been previously investigated.
1035	23460046	Moreover, mitochondrial biogenesis of ob/ob cardiomyocytes is significantly impaired, as evidenced by reduced Ppargc-1a/Nrf-1/Tfam mRNA levels, mitochondrial DNA content, ATP content, citrate synthase activity, complexes I/III/V activity, AMPK phosphorylation, and increased PGC-1α acetylation.
1036	23460046	Since APN is an upstream activator of AMPK and APN plasma levels are significantly reduced in ob/ob mice, we further tested the hypothesis that reduced APN in ob/ob mice is causatively related to mitochondrial biogenesis impairment.
1037	23471027	Discoidal HDL and apoA-I-derived peptides improve glucose uptake in skeletal muscle.
1038	23471027	Increased plasma membrane GLUT4 levels in ex vivo rHDL-stimulated myofibers from HA-GLUT4-GFP transgenic mice support this observation. rHDL increased phosphorylation of AMP kinase (AMPK) and acetyl-coA carboxylase (ACC) but not Akt.
1039	23471027	A survey of domain-specific peptides of apoA-I showed that the lipid-free C-terminal 190-243 fragment increases plasma membrane GLUT4, promotes glucose uptake, and activates AMPK signaling but not Akt.
1040	23471027	Discoidal HDL and apoA-I-derived peptides improve glucose uptake in skeletal muscle.
1041	23471027	Increased plasma membrane GLUT4 levels in ex vivo rHDL-stimulated myofibers from HA-GLUT4-GFP transgenic mice support this observation. rHDL increased phosphorylation of AMP kinase (AMPK) and acetyl-coA carboxylase (ACC) but not Akt.
1042	23471027	A survey of domain-specific peptides of apoA-I showed that the lipid-free C-terminal 190-243 fragment increases plasma membrane GLUT4, promotes glucose uptake, and activates AMPK signaling but not Akt.
1043	23482445	Thus, to explore the function of neuronatin further, we used RNAi to silence its expression in murine primary adipocyte cultures and examined the effects on adipocyte phenotype.
1044	23482445	This was accompanied by increased expression of UCP1 and the key genes in mitochondrial oxidative phosphorylation, PGC-1α, Cox8b, and Cox4 in primary subcutaneous white adipocytes, indicative of a "browning" effect.
1045	23482445	In addition, phosphorylation of AMPK and ACC was increased, suggestive of increased fatty acid utilization.
1046	23482445	In contrast, loss of neuronatin caused a reduction in both basal and insulin-stimulated glucose uptake and glycogen synthesis, likely mediated by a reduction in Glut1 protein upon silencing of neuronatin.
1047	23482445	In contrast, loss of neuronatin had no effect on insulin signaling.
1048	23498665	Mechanistically, polyphenolic compounds including non-flavonoids, such as curcumin and resveratrol, and flavonoids, such as catechins (tea-polyphenols), quercetin and isoflavones, suppress nuclear factor-κB (NF-κB) and mitogen-activated protein (MAP) kinases (MAPK) pathways while activating the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway in adipose tissue.
1049	23498665	These include activation of AMPK and peroxisome proliferator-activated receptor gamma (PPAR-γ), as well as suppression of toll-like receptors (TLRs) and NF-κB pathway.
1050	23498665	Mechanistically, polyphenolic compounds including non-flavonoids, such as curcumin and resveratrol, and flavonoids, such as catechins (tea-polyphenols), quercetin and isoflavones, suppress nuclear factor-κB (NF-κB) and mitogen-activated protein (MAP) kinases (MAPK) pathways while activating the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway in adipose tissue.
1051	23498665	These include activation of AMPK and peroxisome proliferator-activated receptor gamma (PPAR-γ), as well as suppression of toll-like receptors (TLRs) and NF-κB pathway.
1052	23638033	We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo.
1053	23638033	BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20-35%.
1054	23638033	We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo.
1055	23638033	BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20-35%.
1056	23639187	Furthermore, the extracts increased activation of key regulatory proteins (AKT and AMPK) involved in insulin-dependent and non-insulin regulated signalling pathways.
1057	23639187	Inhibition of PKC θ activation and increased activation of AMPK and AKT offer a plausible mechanistic explanation for this ameliorative effect.
1058	23639187	Furthermore, the extracts increased activation of key regulatory proteins (AKT and AMPK) involved in insulin-dependent and non-insulin regulated signalling pathways.
1059	23639187	Inhibition of PKC θ activation and increased activation of AMPK and AKT offer a plausible mechanistic explanation for this ameliorative effect.
1060	23649519	Endothelial nitric oxide synthase (eNOS) dysfunction induces insulin resistance and glucose intolerance.
1061	23649519	In addition, the glucose-lowering effect and activation of AMPK by BH4 did not appear in mice with STZ-induced diabetes lacking eNOS.
1062	23649519	Taken together, BH4 suppresses hepatic gluconeogenesis in an eNOS-dependent manner, and BH4 has a glucose-lowering effect as well as an insulin-sensitizing effect in diabetic mice.
1063	23667692	Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation.
1064	23669253	In addition, IL-6 and TNF-α levels as well as phosphorylation of AMPK, p38, ERK1/2, IKK, and IκB were significantly increased.
1065	23669253	Vitamin D-treated rats showed a significant decrease in plasma CK level, phosphorylation of AMPK, p38, ERK1/2, IKK, and IκB, and gene expression of IL-6 and TNF-α.
1066	23669253	Therefore, we concluded that vitamin D may play a pivotal role in exercise-induced muscle damage and inflammation through the modulation of MAPK and NF-κB involved with VDR.
1067	23669253	In addition, IL-6 and TNF-α levels as well as phosphorylation of AMPK, p38, ERK1/2, IKK, and IκB were significantly increased.
1068	23669253	Vitamin D-treated rats showed a significant decrease in plasma CK level, phosphorylation of AMPK, p38, ERK1/2, IKK, and IκB, and gene expression of IL-6 and TNF-α.
1069	23669253	Therefore, we concluded that vitamin D may play a pivotal role in exercise-induced muscle damage and inflammation through the modulation of MAPK and NF-κB involved with VDR.
1070	23748787	Stilbene analogs of resveratrol improve insulin resistance through activation of AMPK.
1071	23771523	Previously, we showed that metformin prevented tobacco carcinogen (NNK)-induced lung tumorigenesis in a non-diabetic mouse model, which was associated with decreased IGF-I/insulin receptor signaling but not activation of AMPK in lung tissues, as well as decreased circulating levels of IGF-I and insulin.
1072	23773982	Thyroid hormone improves the mechanical performance of the post-infarcted diabetic myocardium: a response associated with up-regulation of Akt/mTOR and AMPK activation.
1073	23819014	Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions.
1074	23842676	CTRP9 is a secreted multimeric protein of the C1q family and the closest paralog of the insulin-sensitizing adipokine, adiponectin.
1075	23842676	Enhanced fat oxidation in CTRP9 transgenic mice resulted from increases in skeletal muscle mitochondrial content, expression of enzymes involved in fatty acid oxidation (LCAD and MCAD), and chronic AMPK activation.
1076	23846758	Orai1 and STIM1 transcription is stimulated by NF-κB (nuclear factor kappa B).
1077	23846758	Serum- and glucocorticoid-inducible kinase 1 (SGK1) up-regulates NF-κB-activity in megakaryocytes and thus Orai1-expression and SOCE in platelets.
1078	23846758	Additional potential regulators of Orai1/STIM1 and thus SOCE in platelets include AMP activated kinase (AMPK), protein kinase A (PKA), reactive oxygen species, lipid rafts, pH and mitochondrial Ca2+ buffering.
1079	23859619	Although AMPK activation inhibits tumor growth by targeting multiple signaling pathways relevant to tumorigenesis, under certain cellular contexts or certain stages of tumor development, AMPK might act as a protective response to metabolic stresses, such as nutrient deprivation, low oxygen, and low pH, or as downstream effectors of oncogenic proteins, including androgen receptor, hypoxia-inducible factor-1α, c-Src, and MYC.
1080	23864882	Phosphorylation of AMP-dependent protein kinase (AMPK), Akt, and Glycogen synthase kinase-3 (GSK-3) were probed by Western blot.
1081	23864882	This action involved both Akt and AMPK phosphorylation.
1082	23864882	Phosphorylation of AMP-dependent protein kinase (AMPK), Akt, and Glycogen synthase kinase-3 (GSK-3) were probed by Western blot.
1083	23864882	This action involved both Akt and AMPK phosphorylation.
1084	23879009	Influencing the transduction mechanisms primarily through activation of protein kinase activated by 5'AMP (AMPK) regulates the activity of the AMPK/mTOR signaling pathway.
1085	23879009	Metformin has antiproliferative properties; reduces the VEGF levels, causing a reduction in tumor vasculature; causes an increase in progesterone receptor, which increases the response to hormonal therapy; inhibits the expression of glyoxalase I, mediating resistance to chemotherapy; decreases in the concentration of human telomerase; reduces the activity of Akt and Erk kinases, key regulators of metabolism and progression of tumors and also inhibits the formation of metastases.
1086	23891087	Contributions of AMPK and p53 dependent signaling to radiation response in the presence of metformin.
1087	23973646	Intracerebroventricular treatment with the AMPK activator AICAR increased blood glucose levels in the glucose tolerance test, and this increase was inhibited by compound C.