Ignet

Gene Information

Gene symbol: ATIC

Gene name: 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase

HGNC ID: 794

Synonyms: PURH, AICARFT, IMPCHASE

Related Genes

#	Gene Symbol	Number of hits
1	ACACA	1 hits
2	ACACB	1 hits
3	ADIPOQ	1 hits
4	AKT1	1 hits
5	ATM	1 hits
6	CD36	1 hits
7	CNBP	1 hits
8	CSK	1 hits
9	DUSP9	1 hits
10	FASN	1 hits
11	GCK	1 hits
12	GLP1R	1 hits
13	GTF3A	1 hits
14	IL6	1 hits
15	INS	1 hits
16	IRS1	1 hits
17	JUN	1 hits
18	LEP	1 hits
19	LPIN1	1 hits
20	LPL	1 hits
21	MAPK1	1 hits
22	MAPK10	1 hits
23	MAPK14	1 hits
24	MAPK3	1 hits
25	MAPK6	1 hits
26	MAPK8	1 hits
27	MAPT	1 hits
28	MARK2	1 hits
29	MARK4	1 hits
30	MDM2	1 hits
31	MLYCD	1 hits
32	NFKB1	1 hits
33	NFKBIA	1 hits
34	NOS1	1 hits
35	NOS2A	1 hits
36	NOS3	1 hits
37	NRF1	1 hits
38	NRIP1	1 hits
39	PCK2	1 hits
40	PDK4	1 hits
41	PDPK1	1 hits
42	PIK3CA	1 hits
43	PLCG1	1 hits
44	PPARG	1 hits
45	PPARGC1A	1 hits
46	PRKAA1	1 hits
47	PRKAA2	1 hits
48	PRKAR1A	1 hits
49	PYGM	1 hits
50	RORC	1 hits
51	SLC2A4	1 hits
52	SNF1LK2	1 hits
53	SOCS3	1 hits
54	SOD2	1 hits
55	STAT3	1 hits
56	STK11	1 hits
57	TBC1D1	1 hits
58	TBC1D4	1 hits
59	TFAM	1 hits
60	TP53	1 hits
61	UCP1	1 hits
62	USF1	1 hits
63	VCAM1	1 hits

Related Sentences

#	PMID	Sentence
1	9703344	This hypothesis was based on recent studies showing the following: 1) muscle contraction increases AMPK activity and 2) perfusion of rat hindlimb skeletal muscles with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that results in increased AMPK activity, increased insulin-stimulated glucose uptake.
2	9703344	In the current study, isolated rat epitrochlearis muscles were treated to contract in vitro (via electrical stimulation for 10 min) and/or incubated in the absence or presence of AICAR (2 mmol/l), insulin (1 micromol/l), or wortmannin (100 nmol/l).
3	9703344	Both contraction and AICAR significantly increased AMPK activity, while the enzyme was not activated by insulin.
4	9703344	AICAR, contraction, and insulin all increased 3-O-methylglucose (3MG) transport by threefold to fivefold above basal.
5	9703344	The phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin completely blocked insulin-stimulated transport, but did not inhibit AICAR- or contraction-stimulated transport.
6	9703344	The increase in glucose transport with the combination of maximal AICAR plus maximal insulin treatments was partially additive, suggesting that these stimuli increase glucose transport by different mechanisms.
7	9703344	These data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake.
8	9703344	This hypothesis was based on recent studies showing the following: 1) muscle contraction increases AMPK activity and 2) perfusion of rat hindlimb skeletal muscles with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that results in increased AMPK activity, increased insulin-stimulated glucose uptake.
9	9703344	In the current study, isolated rat epitrochlearis muscles were treated to contract in vitro (via electrical stimulation for 10 min) and/or incubated in the absence or presence of AICAR (2 mmol/l), insulin (1 micromol/l), or wortmannin (100 nmol/l).
10	9703344	Both contraction and AICAR significantly increased AMPK activity, while the enzyme was not activated by insulin.
11	9703344	AICAR, contraction, and insulin all increased 3-O-methylglucose (3MG) transport by threefold to fivefold above basal.
12	9703344	The phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin completely blocked insulin-stimulated transport, but did not inhibit AICAR- or contraction-stimulated transport.
13	9703344	The increase in glucose transport with the combination of maximal AICAR plus maximal insulin treatments was partially additive, suggesting that these stimuli increase glucose transport by different mechanisms.
14	9703344	These data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake.
15	9703344	This hypothesis was based on recent studies showing the following: 1) muscle contraction increases AMPK activity and 2) perfusion of rat hindlimb skeletal muscles with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that results in increased AMPK activity, increased insulin-stimulated glucose uptake.
16	9703344	In the current study, isolated rat epitrochlearis muscles were treated to contract in vitro (via electrical stimulation for 10 min) and/or incubated in the absence or presence of AICAR (2 mmol/l), insulin (1 micromol/l), or wortmannin (100 nmol/l).
17	9703344	Both contraction and AICAR significantly increased AMPK activity, while the enzyme was not activated by insulin.
18	9703344	AICAR, contraction, and insulin all increased 3-O-methylglucose (3MG) transport by threefold to fivefold above basal.
19	9703344	The phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin completely blocked insulin-stimulated transport, but did not inhibit AICAR- or contraction-stimulated transport.
20	9703344	The increase in glucose transport with the combination of maximal AICAR plus maximal insulin treatments was partially additive, suggesting that these stimuli increase glucose transport by different mechanisms.
21	9703344	These data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake.
22	9703344	This hypothesis was based on recent studies showing the following: 1) muscle contraction increases AMPK activity and 2) perfusion of rat hindlimb skeletal muscles with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that results in increased AMPK activity, increased insulin-stimulated glucose uptake.
23	9703344	In the current study, isolated rat epitrochlearis muscles were treated to contract in vitro (via electrical stimulation for 10 min) and/or incubated in the absence or presence of AICAR (2 mmol/l), insulin (1 micromol/l), or wortmannin (100 nmol/l).
24	9703344	Both contraction and AICAR significantly increased AMPK activity, while the enzyme was not activated by insulin.
25	9703344	AICAR, contraction, and insulin all increased 3-O-methylglucose (3MG) transport by threefold to fivefold above basal.
26	9703344	The phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin completely blocked insulin-stimulated transport, but did not inhibit AICAR- or contraction-stimulated transport.
27	9703344	The increase in glucose transport with the combination of maximal AICAR plus maximal insulin treatments was partially additive, suggesting that these stimuli increase glucose transport by different mechanisms.
28	9703344	These data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake.
29	9703344	This hypothesis was based on recent studies showing the following: 1) muscle contraction increases AMPK activity and 2) perfusion of rat hindlimb skeletal muscles with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that results in increased AMPK activity, increased insulin-stimulated glucose uptake.
30	9703344	In the current study, isolated rat epitrochlearis muscles were treated to contract in vitro (via electrical stimulation for 10 min) and/or incubated in the absence or presence of AICAR (2 mmol/l), insulin (1 micromol/l), or wortmannin (100 nmol/l).
31	9703344	Both contraction and AICAR significantly increased AMPK activity, while the enzyme was not activated by insulin.
32	9703344	AICAR, contraction, and insulin all increased 3-O-methylglucose (3MG) transport by threefold to fivefold above basal.
33	9703344	The phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin completely blocked insulin-stimulated transport, but did not inhibit AICAR- or contraction-stimulated transport.
34	9703344	The increase in glucose transport with the combination of maximal AICAR plus maximal insulin treatments was partially additive, suggesting that these stimuli increase glucose transport by different mechanisms.
35	9703344	These data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake.
36	9703344	This hypothesis was based on recent studies showing the following: 1) muscle contraction increases AMPK activity and 2) perfusion of rat hindlimb skeletal muscles with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that results in increased AMPK activity, increased insulin-stimulated glucose uptake.
37	9703344	In the current study, isolated rat epitrochlearis muscles were treated to contract in vitro (via electrical stimulation for 10 min) and/or incubated in the absence or presence of AICAR (2 mmol/l), insulin (1 micromol/l), or wortmannin (100 nmol/l).
38	9703344	Both contraction and AICAR significantly increased AMPK activity, while the enzyme was not activated by insulin.
39	9703344	AICAR, contraction, and insulin all increased 3-O-methylglucose (3MG) transport by threefold to fivefold above basal.
40	9703344	The phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin completely blocked insulin-stimulated transport, but did not inhibit AICAR- or contraction-stimulated transport.
41	9703344	The increase in glucose transport with the combination of maximal AICAR plus maximal insulin treatments was partially additive, suggesting that these stimuli increase glucose transport by different mechanisms.
42	9703344	These data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake.
43	9703344	This hypothesis was based on recent studies showing the following: 1) muscle contraction increases AMPK activity and 2) perfusion of rat hindlimb skeletal muscles with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that results in increased AMPK activity, increased insulin-stimulated glucose uptake.
44	9703344	In the current study, isolated rat epitrochlearis muscles were treated to contract in vitro (via electrical stimulation for 10 min) and/or incubated in the absence or presence of AICAR (2 mmol/l), insulin (1 micromol/l), or wortmannin (100 nmol/l).
45	9703344	Both contraction and AICAR significantly increased AMPK activity, while the enzyme was not activated by insulin.
46	9703344	AICAR, contraction, and insulin all increased 3-O-methylglucose (3MG) transport by threefold to fivefold above basal.
47	9703344	The phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin completely blocked insulin-stimulated transport, but did not inhibit AICAR- or contraction-stimulated transport.
48	9703344	The increase in glucose transport with the combination of maximal AICAR plus maximal insulin treatments was partially additive, suggesting that these stimuli increase glucose transport by different mechanisms.
49	9703344	These data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake.
50	10866040	5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase.
51	10866040	Insulin regulates the rate of expression of many hepatic genes, including PEPCK, glucose-6-phosphatase (G6Pase), and glucose-6-phosphate dehydrogenase (G6PDHase).
52	10866040	We demonstrate here that treatment of hepatoma cells with 5-aminoimidazole-4-carboxamide riboside (AICAR), an agent that activates AMP-activated protein kinase (AMPK), mimics the ability of insulin to repress PEPCK gene transcription.
53	10866040	Several lines of evidence suggest that the insulin-mimetic effects of AICAR are mediated by activation of AMPK.
54	10866040	Also, insulin does not activate AMPK in H4IIE cells, suggesting that this protein kinase does not link the insulin receptor to the PEPCK and G6Pase gene promoters.
55	10866040	Instead, AMPK and insulin may lie on distinct pathways that converge at a point upstream of these 2 gene promoters.
56	10866040	Our results also suggest that activation of AMPK would inhibit hepatic gluconeogenesis in an insulin-independent manner and thus help to reverse the hyperglycemia associated with type 2 diabetes.
57	10866040	5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase.
58	10866040	Insulin regulates the rate of expression of many hepatic genes, including PEPCK, glucose-6-phosphatase (G6Pase), and glucose-6-phosphate dehydrogenase (G6PDHase).
59	10866040	We demonstrate here that treatment of hepatoma cells with 5-aminoimidazole-4-carboxamide riboside (AICAR), an agent that activates AMP-activated protein kinase (AMPK), mimics the ability of insulin to repress PEPCK gene transcription.
60	10866040	Several lines of evidence suggest that the insulin-mimetic effects of AICAR are mediated by activation of AMPK.
61	10866040	Also, insulin does not activate AMPK in H4IIE cells, suggesting that this protein kinase does not link the insulin receptor to the PEPCK and G6Pase gene promoters.
62	10866040	Instead, AMPK and insulin may lie on distinct pathways that converge at a point upstream of these 2 gene promoters.
63	10866040	Our results also suggest that activation of AMPK would inhibit hepatic gluconeogenesis in an insulin-independent manner and thus help to reverse the hyperglycemia associated with type 2 diabetes.
64	11016448	5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes.
65	11016448	Incubation of skeletal muscle with 5-aminoimidazole-4carboxamide ribonucleoside (AICAR), a compound that activates 5'-AMP-activated protein kinase (AMPK), has been demonstrated to stimulate glucose transport and GLUT4 translocation to the plasma membrane.
66	11016448	In this study, we characterized the AMPK cascade in 3T3-L1 adipocytes and the response of glucose transport to incubation with AICAR.
67	11016448	Both isoforms of the catalytic alpha-subunit of AMPK are expressed in 3T3-L1 adipocytes, in which AICAR stimulated AMPK activity in a time- and dose-dependent fashion.
68	11016448	AICAR stimulated 2-deoxy-D-glucose transport twofold and reduced insulin-stimulated uptake to 62% of the control transport rate dose-dependently, closely correlating with the activation of AMPK.
69	11016448	AICAR also inhibited insulin-stimulated GLUT4 translocation, assessed using the plasma membrane lawn assay.
70	11016448	The effects of AICAR on insulin-stimulated glucose transport are not mediated by either adenosine receptors or nitric oxide synthase and are mediated downstream of phosphatidylinositol 3'-kinase stimulation.
71	11016448	We propose that in contrast to skeletal muscle, in which AMPK stimulation promotes glucose transport to provide ATP as a fuel, AMPK stimulation inhibits insulin-stimulated glucose transport in adipocytes, inhibiting triacylglycerol synthesis, to conserve ATP under conditions of cellular stress.
72	11016448	Investigation of the mode of action of AICAR and AMPK may, therefore, give insight into the mechanism of insulin action.
73	11016448	5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes.
74	11016448	Incubation of skeletal muscle with 5-aminoimidazole-4carboxamide ribonucleoside (AICAR), a compound that activates 5'-AMP-activated protein kinase (AMPK), has been demonstrated to stimulate glucose transport and GLUT4 translocation to the plasma membrane.
75	11016448	In this study, we characterized the AMPK cascade in 3T3-L1 adipocytes and the response of glucose transport to incubation with AICAR.
76	11016448	Both isoforms of the catalytic alpha-subunit of AMPK are expressed in 3T3-L1 adipocytes, in which AICAR stimulated AMPK activity in a time- and dose-dependent fashion.
77	11016448	AICAR stimulated 2-deoxy-D-glucose transport twofold and reduced insulin-stimulated uptake to 62% of the control transport rate dose-dependently, closely correlating with the activation of AMPK.
78	11016448	AICAR also inhibited insulin-stimulated GLUT4 translocation, assessed using the plasma membrane lawn assay.
79	11016448	The effects of AICAR on insulin-stimulated glucose transport are not mediated by either adenosine receptors or nitric oxide synthase and are mediated downstream of phosphatidylinositol 3'-kinase stimulation.
80	11016448	We propose that in contrast to skeletal muscle, in which AMPK stimulation promotes glucose transport to provide ATP as a fuel, AMPK stimulation inhibits insulin-stimulated glucose transport in adipocytes, inhibiting triacylglycerol synthesis, to conserve ATP under conditions of cellular stress.
81	11016448	Investigation of the mode of action of AICAR and AMPK may, therefore, give insight into the mechanism of insulin action.
82	11016448	5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes.
83	11016448	Incubation of skeletal muscle with 5-aminoimidazole-4carboxamide ribonucleoside (AICAR), a compound that activates 5'-AMP-activated protein kinase (AMPK), has been demonstrated to stimulate glucose transport and GLUT4 translocation to the plasma membrane.
84	11016448	In this study, we characterized the AMPK cascade in 3T3-L1 adipocytes and the response of glucose transport to incubation with AICAR.
85	11016448	Both isoforms of the catalytic alpha-subunit of AMPK are expressed in 3T3-L1 adipocytes, in which AICAR stimulated AMPK activity in a time- and dose-dependent fashion.
86	11016448	AICAR stimulated 2-deoxy-D-glucose transport twofold and reduced insulin-stimulated uptake to 62% of the control transport rate dose-dependently, closely correlating with the activation of AMPK.
87	11016448	AICAR also inhibited insulin-stimulated GLUT4 translocation, assessed using the plasma membrane lawn assay.
88	11016448	The effects of AICAR on insulin-stimulated glucose transport are not mediated by either adenosine receptors or nitric oxide synthase and are mediated downstream of phosphatidylinositol 3'-kinase stimulation.
89	11016448	We propose that in contrast to skeletal muscle, in which AMPK stimulation promotes glucose transport to provide ATP as a fuel, AMPK stimulation inhibits insulin-stimulated glucose transport in adipocytes, inhibiting triacylglycerol synthesis, to conserve ATP under conditions of cellular stress.
90	11016448	Investigation of the mode of action of AICAR and AMPK may, therefore, give insight into the mechanism of insulin action.
91	11016448	5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes.
92	11016448	Incubation of skeletal muscle with 5-aminoimidazole-4carboxamide ribonucleoside (AICAR), a compound that activates 5'-AMP-activated protein kinase (AMPK), has been demonstrated to stimulate glucose transport and GLUT4 translocation to the plasma membrane.
93	11016448	In this study, we characterized the AMPK cascade in 3T3-L1 adipocytes and the response of glucose transport to incubation with AICAR.
94	11016448	Both isoforms of the catalytic alpha-subunit of AMPK are expressed in 3T3-L1 adipocytes, in which AICAR stimulated AMPK activity in a time- and dose-dependent fashion.
95	11016448	AICAR stimulated 2-deoxy-D-glucose transport twofold and reduced insulin-stimulated uptake to 62% of the control transport rate dose-dependently, closely correlating with the activation of AMPK.
96	11016448	AICAR also inhibited insulin-stimulated GLUT4 translocation, assessed using the plasma membrane lawn assay.
97	11016448	The effects of AICAR on insulin-stimulated glucose transport are not mediated by either adenosine receptors or nitric oxide synthase and are mediated downstream of phosphatidylinositol 3'-kinase stimulation.
98	11016448	We propose that in contrast to skeletal muscle, in which AMPK stimulation promotes glucose transport to provide ATP as a fuel, AMPK stimulation inhibits insulin-stimulated glucose transport in adipocytes, inhibiting triacylglycerol synthesis, to conserve ATP under conditions of cellular stress.
99	11016448	Investigation of the mode of action of AICAR and AMPK may, therefore, give insight into the mechanism of insulin action.
100	11016448	5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes.
101	11016448	Incubation of skeletal muscle with 5-aminoimidazole-4carboxamide ribonucleoside (AICAR), a compound that activates 5'-AMP-activated protein kinase (AMPK), has been demonstrated to stimulate glucose transport and GLUT4 translocation to the plasma membrane.
102	11016448	In this study, we characterized the AMPK cascade in 3T3-L1 adipocytes and the response of glucose transport to incubation with AICAR.
103	11016448	Both isoforms of the catalytic alpha-subunit of AMPK are expressed in 3T3-L1 adipocytes, in which AICAR stimulated AMPK activity in a time- and dose-dependent fashion.
104	11016448	AICAR stimulated 2-deoxy-D-glucose transport twofold and reduced insulin-stimulated uptake to 62% of the control transport rate dose-dependently, closely correlating with the activation of AMPK.
105	11016448	AICAR also inhibited insulin-stimulated GLUT4 translocation, assessed using the plasma membrane lawn assay.
106	11016448	The effects of AICAR on insulin-stimulated glucose transport are not mediated by either adenosine receptors or nitric oxide synthase and are mediated downstream of phosphatidylinositol 3'-kinase stimulation.
107	11016448	We propose that in contrast to skeletal muscle, in which AMPK stimulation promotes glucose transport to provide ATP as a fuel, AMPK stimulation inhibits insulin-stimulated glucose transport in adipocytes, inhibiting triacylglycerol synthesis, to conserve ATP under conditions of cellular stress.
108	11016448	Investigation of the mode of action of AICAR and AMPK may, therefore, give insight into the mechanism of insulin action.
109	11016448	5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes.
110	11016448	Incubation of skeletal muscle with 5-aminoimidazole-4carboxamide ribonucleoside (AICAR), a compound that activates 5'-AMP-activated protein kinase (AMPK), has been demonstrated to stimulate glucose transport and GLUT4 translocation to the plasma membrane.
111	11016448	In this study, we characterized the AMPK cascade in 3T3-L1 adipocytes and the response of glucose transport to incubation with AICAR.
112	11016448	Both isoforms of the catalytic alpha-subunit of AMPK are expressed in 3T3-L1 adipocytes, in which AICAR stimulated AMPK activity in a time- and dose-dependent fashion.
113	11016448	AICAR stimulated 2-deoxy-D-glucose transport twofold and reduced insulin-stimulated uptake to 62% of the control transport rate dose-dependently, closely correlating with the activation of AMPK.
114	11016448	AICAR also inhibited insulin-stimulated GLUT4 translocation, assessed using the plasma membrane lawn assay.
115	11016448	The effects of AICAR on insulin-stimulated glucose transport are not mediated by either adenosine receptors or nitric oxide synthase and are mediated downstream of phosphatidylinositol 3'-kinase stimulation.
116	11016448	We propose that in contrast to skeletal muscle, in which AMPK stimulation promotes glucose transport to provide ATP as a fuel, AMPK stimulation inhibits insulin-stimulated glucose transport in adipocytes, inhibiting triacylglycerol synthesis, to conserve ATP under conditions of cellular stress.
117	11016448	Investigation of the mode of action of AICAR and AMPK may, therefore, give insight into the mechanism of insulin action.
118	11016448	5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes.
119	11016448	Incubation of skeletal muscle with 5-aminoimidazole-4carboxamide ribonucleoside (AICAR), a compound that activates 5'-AMP-activated protein kinase (AMPK), has been demonstrated to stimulate glucose transport and GLUT4 translocation to the plasma membrane.
120	11016448	In this study, we characterized the AMPK cascade in 3T3-L1 adipocytes and the response of glucose transport to incubation with AICAR.
121	11016448	Both isoforms of the catalytic alpha-subunit of AMPK are expressed in 3T3-L1 adipocytes, in which AICAR stimulated AMPK activity in a time- and dose-dependent fashion.
122	11016448	AICAR stimulated 2-deoxy-D-glucose transport twofold and reduced insulin-stimulated uptake to 62% of the control transport rate dose-dependently, closely correlating with the activation of AMPK.
123	11016448	AICAR also inhibited insulin-stimulated GLUT4 translocation, assessed using the plasma membrane lawn assay.
124	11016448	The effects of AICAR on insulin-stimulated glucose transport are not mediated by either adenosine receptors or nitric oxide synthase and are mediated downstream of phosphatidylinositol 3'-kinase stimulation.
125	11016448	We propose that in contrast to skeletal muscle, in which AMPK stimulation promotes glucose transport to provide ATP as a fuel, AMPK stimulation inhibits insulin-stimulated glucose transport in adipocytes, inhibiting triacylglycerol synthesis, to conserve ATP under conditions of cellular stress.
126	11016448	Investigation of the mode of action of AICAR and AMPK may, therefore, give insight into the mechanism of insulin action.
127	11016448	5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes.
128	11016448	Incubation of skeletal muscle with 5-aminoimidazole-4carboxamide ribonucleoside (AICAR), a compound that activates 5'-AMP-activated protein kinase (AMPK), has been demonstrated to stimulate glucose transport and GLUT4 translocation to the plasma membrane.
129	11016448	In this study, we characterized the AMPK cascade in 3T3-L1 adipocytes and the response of glucose transport to incubation with AICAR.
130	11016448	Both isoforms of the catalytic alpha-subunit of AMPK are expressed in 3T3-L1 adipocytes, in which AICAR stimulated AMPK activity in a time- and dose-dependent fashion.
131	11016448	AICAR stimulated 2-deoxy-D-glucose transport twofold and reduced insulin-stimulated uptake to 62% of the control transport rate dose-dependently, closely correlating with the activation of AMPK.
132	11016448	AICAR also inhibited insulin-stimulated GLUT4 translocation, assessed using the plasma membrane lawn assay.
133	11016448	The effects of AICAR on insulin-stimulated glucose transport are not mediated by either adenosine receptors or nitric oxide synthase and are mediated downstream of phosphatidylinositol 3'-kinase stimulation.
134	11016448	We propose that in contrast to skeletal muscle, in which AMPK stimulation promotes glucose transport to provide ATP as a fuel, AMPK stimulation inhibits insulin-stimulated glucose transport in adipocytes, inhibiting triacylglycerol synthesis, to conserve ATP under conditions of cellular stress.
135	11016448	Investigation of the mode of action of AICAR and AMPK may, therefore, give insight into the mechanism of insulin action.
136	11147776	Chronic treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner.
137	11147776	Recent studies have demonstrated that chronic administration of AICAR (5-aminoimidazole-4-carboxamide- 1-beta-D-ribofuranoside), an activator of the AMP-activated protein kinase, increases hexokinase activity and the contents of total GLUT4 and glycogen in rat skeletal muscles.
138	11147776	To explore whether AICAR also affects insulin-stimulated glucose transport and GLUT4 cell surface content, Wistar rats were subcutaneously injected with AICAR for 5 days in succession (1 mg/g body wt).
139	11147776	In contrast, administration of AICAR did not maximally influence insulin-stimulated glucose transport in soleus muscle.
140	11147776	Studies of EPI muscle with the 4,4'-O-[2-[2-[2-[2-[2-[6-(biotinylamino)hexanoyl]amino]ethoxy]ethoxy] ethoxy]-4-(1-azi-2,2,2,-trifluoroethyl)benzoyl]amino-1,3-propanediyl]bis-D-mannose photolabeling technique showed a concomitant increase (average 68%, P < 0.02) in cell surface GLUT4 content after insulin exposure in AICAR-injected rats when compared with controls.
141	11147776	In conclusion, 5 days of AICAR administration induces a pronounced fiber type-specific increase in insulin-stimulated glucose uptake and GLUT4 cell surface content in rat skeletal muscle with the greatest effect observed on white fast-twitch glycolytic muscles (EPI).
142	11147776	These results are comparable with the effects of chronic exercise training, and it brings the AMP-activated protein kinase into focus as a new interesting target for future pharmacological intervention in insulin-resistant conditions.
143	11147776	Chronic treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner.
144	11147776	Recent studies have demonstrated that chronic administration of AICAR (5-aminoimidazole-4-carboxamide- 1-beta-D-ribofuranoside), an activator of the AMP-activated protein kinase, increases hexokinase activity and the contents of total GLUT4 and glycogen in rat skeletal muscles.
145	11147776	To explore whether AICAR also affects insulin-stimulated glucose transport and GLUT4 cell surface content, Wistar rats were subcutaneously injected with AICAR for 5 days in succession (1 mg/g body wt).
146	11147776	In contrast, administration of AICAR did not maximally influence insulin-stimulated glucose transport in soleus muscle.
147	11147776	Studies of EPI muscle with the 4,4'-O-[2-[2-[2-[2-[2-[6-(biotinylamino)hexanoyl]amino]ethoxy]ethoxy] ethoxy]-4-(1-azi-2,2,2,-trifluoroethyl)benzoyl]amino-1,3-propanediyl]bis-D-mannose photolabeling technique showed a concomitant increase (average 68%, P < 0.02) in cell surface GLUT4 content after insulin exposure in AICAR-injected rats when compared with controls.
148	11147776	In conclusion, 5 days of AICAR administration induces a pronounced fiber type-specific increase in insulin-stimulated glucose uptake and GLUT4 cell surface content in rat skeletal muscle with the greatest effect observed on white fast-twitch glycolytic muscles (EPI).
149	11147776	These results are comparable with the effects of chronic exercise training, and it brings the AMP-activated protein kinase into focus as a new interesting target for future pharmacological intervention in insulin-resistant conditions.
150	11147776	Chronic treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner.
151	11147776	Recent studies have demonstrated that chronic administration of AICAR (5-aminoimidazole-4-carboxamide- 1-beta-D-ribofuranoside), an activator of the AMP-activated protein kinase, increases hexokinase activity and the contents of total GLUT4 and glycogen in rat skeletal muscles.
152	11147776	To explore whether AICAR also affects insulin-stimulated glucose transport and GLUT4 cell surface content, Wistar rats were subcutaneously injected with AICAR for 5 days in succession (1 mg/g body wt).
153	11147776	In contrast, administration of AICAR did not maximally influence insulin-stimulated glucose transport in soleus muscle.
154	11147776	Studies of EPI muscle with the 4,4'-O-[2-[2-[2-[2-[2-[6-(biotinylamino)hexanoyl]amino]ethoxy]ethoxy] ethoxy]-4-(1-azi-2,2,2,-trifluoroethyl)benzoyl]amino-1,3-propanediyl]bis-D-mannose photolabeling technique showed a concomitant increase (average 68%, P < 0.02) in cell surface GLUT4 content after insulin exposure in AICAR-injected rats when compared with controls.
155	11147776	In conclusion, 5 days of AICAR administration induces a pronounced fiber type-specific increase in insulin-stimulated glucose uptake and GLUT4 cell surface content in rat skeletal muscle with the greatest effect observed on white fast-twitch glycolytic muscles (EPI).
156	11147776	These results are comparable with the effects of chronic exercise training, and it brings the AMP-activated protein kinase into focus as a new interesting target for future pharmacological intervention in insulin-resistant conditions.
157	11147776	Chronic treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner.
158	11147776	Recent studies have demonstrated that chronic administration of AICAR (5-aminoimidazole-4-carboxamide- 1-beta-D-ribofuranoside), an activator of the AMP-activated protein kinase, increases hexokinase activity and the contents of total GLUT4 and glycogen in rat skeletal muscles.
159	11147776	To explore whether AICAR also affects insulin-stimulated glucose transport and GLUT4 cell surface content, Wistar rats were subcutaneously injected with AICAR for 5 days in succession (1 mg/g body wt).
160	11147776	In contrast, administration of AICAR did not maximally influence insulin-stimulated glucose transport in soleus muscle.
161	11147776	Studies of EPI muscle with the 4,4'-O-[2-[2-[2-[2-[2-[6-(biotinylamino)hexanoyl]amino]ethoxy]ethoxy] ethoxy]-4-(1-azi-2,2,2,-trifluoroethyl)benzoyl]amino-1,3-propanediyl]bis-D-mannose photolabeling technique showed a concomitant increase (average 68%, P < 0.02) in cell surface GLUT4 content after insulin exposure in AICAR-injected rats when compared with controls.
162	11147776	In conclusion, 5 days of AICAR administration induces a pronounced fiber type-specific increase in insulin-stimulated glucose uptake and GLUT4 cell surface content in rat skeletal muscle with the greatest effect observed on white fast-twitch glycolytic muscles (EPI).
163	11147776	These results are comparable with the effects of chronic exercise training, and it brings the AMP-activated protein kinase into focus as a new interesting target for future pharmacological intervention in insulin-resistant conditions.
164	11147776	Chronic treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner.
165	11147776	Recent studies have demonstrated that chronic administration of AICAR (5-aminoimidazole-4-carboxamide- 1-beta-D-ribofuranoside), an activator of the AMP-activated protein kinase, increases hexokinase activity and the contents of total GLUT4 and glycogen in rat skeletal muscles.
166	11147776	To explore whether AICAR also affects insulin-stimulated glucose transport and GLUT4 cell surface content, Wistar rats were subcutaneously injected with AICAR for 5 days in succession (1 mg/g body wt).
167	11147776	In contrast, administration of AICAR did not maximally influence insulin-stimulated glucose transport in soleus muscle.
168	11147776	Studies of EPI muscle with the 4,4'-O-[2-[2-[2-[2-[2-[6-(biotinylamino)hexanoyl]amino]ethoxy]ethoxy] ethoxy]-4-(1-azi-2,2,2,-trifluoroethyl)benzoyl]amino-1,3-propanediyl]bis-D-mannose photolabeling technique showed a concomitant increase (average 68%, P < 0.02) in cell surface GLUT4 content after insulin exposure in AICAR-injected rats when compared with controls.
169	11147776	In conclusion, 5 days of AICAR administration induces a pronounced fiber type-specific increase in insulin-stimulated glucose uptake and GLUT4 cell surface content in rat skeletal muscle with the greatest effect observed on white fast-twitch glycolytic muscles (EPI).
170	11147776	These results are comparable with the effects of chronic exercise training, and it brings the AMP-activated protein kinase into focus as a new interesting target for future pharmacological intervention in insulin-resistant conditions.
171	11287349	The AMP-activated protein kinase (AMPK) has been hypothesized to mediate contraction and 5-aminoimidazole-4-carboxamide 1-beta-D-ribonucleoside (AICAR)-induced increases in glucose uptake in skeletal muscle.
172	11287349	In isolated muscles, the putative AMPK inhibitors ara-A, 8-bromo-AMP, and iodotubercidin fully inhibited AICAR-stimulated AMPK alpha 2 activity and 3-MG uptake but had little effect on AMPK alpha 1 activity.
173	11287349	The AMP-activated protein kinase (AMPK) has been hypothesized to mediate contraction and 5-aminoimidazole-4-carboxamide 1-beta-D-ribonucleoside (AICAR)-induced increases in glucose uptake in skeletal muscle.
174	11287349	In isolated muscles, the putative AMPK inhibitors ara-A, 8-bromo-AMP, and iodotubercidin fully inhibited AICAR-stimulated AMPK alpha 2 activity and 3-MG uptake but had little effect on AMPK alpha 1 activity.
175	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
176	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
177	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
178	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
179	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
180	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
181	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
182	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
183	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
184	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
185	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
186	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
187	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
188	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
189	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
190	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
191	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
192	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
193	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
194	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
195	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
196	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
197	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
198	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
199	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
200	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
201	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
202	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
203	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
204	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
205	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
206	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
207	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
208	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
209	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
210	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
211	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
212	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
213	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
214	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
215	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
216	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
217	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
218	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
219	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
220	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
221	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
222	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
223	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
224	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
225	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
226	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
227	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
228	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
229	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
230	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
231	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
232	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
233	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
234	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
235	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
236	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
237	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
238	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
239	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
240	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
241	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
242	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
243	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
244	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
245	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
246	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
247	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
248	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
249	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
250	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
251	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
252	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
253	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
254	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
255	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
256	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
257	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
258	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
259	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
260	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
261	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
262	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
263	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
264	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
265	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
266	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
267	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
268	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
269	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
270	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
271	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
272	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
273	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
274	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
275	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
276	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
277	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
278	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
279	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
280	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
281	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
282	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
283	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
284	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
285	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
286	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
287	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
288	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
289	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
290	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
291	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
292	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
293	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
294	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
295	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
296	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
297	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
298	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
299	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
300	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
301	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
302	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
303	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
304	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
305	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
306	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
307	11334411	Activation of AMP-activated protein kinase (AMPK) with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofurano-side (AICAR) increases glucose transport in skeletal muscle via an insulin-independent pathway.
308	11334411	To examine the effects of AMPK activation on skeletal muscle glucose transport activity and whole-body carbohydrate and lipid metabolism in an insulin-resistant rat model, awake obese Zuckerfa/fa rats (n = 26) and their lean (n = 23) littermates were infused for 90 min with AICAR, insulin, or saline.
309	11334411	The insulin infusion rate (4 mU.kg(-1).min(-1)) was selected to match the glucose requirements during AICAR (bolus, 100 mg/kg; constant, 10 mg.kg(-1).min(-1)) isoglycemic clamps in the lean rats.
310	11334411	The effects of these identical AICAR and insulin infusion rates were then examined in the obese Zucker rats.
311	11334411	AICAR infusion increased muscle AMPK activity more than fivefold (P < 0.01 vs. control and insulin) in both lean and obese rats.
312	11334411	Plasma triglycerides, fatty acid concentrations, and glycerol turnover, as assessed by [2-13C]glycerol, were all decreased in both lean and obese rats infused with AICAR (P < 0.05 vs. basal), whereas insulin had no effect on these parameters in the obese rats.
313	11334411	Endogenous glucose production rates, measured by [U-13C]glucose, were suppressed by >50% during AICAR and insulin infusions in both lean and obese rats (P < 0.05 vs. basal).
314	11334411	In lean rats, rates of whole-body glucose disposal increased by more than two-fold (P < 0.05 vs. basal) during both AICAR and insulin infusion; [3H]2-deoxy-D-glucose transport activity increased to a similar extent, by >2.2-fold (both P < 0.05 vs. control), in both soleus and red gastrocnemius muscles of lean rats infused with either AICAR or insulin.
315	11334411	In the obese Zucker rats, neither AICAR nor insulin stimulated whole-body glucose disposal or soleus muscle glucose transport activity.
316	11334411	However, AICAR increased glucose transport activity by approximately 2.4-fold (P < 0.05 vs. control) in the red gastrocnemius from obese rats, whereas insulin had no effect.
317	11334411	In summary, acute infusion of AICAR in an insulin-resistant rat model activates skeletal muscle AMPK and increases glucose transport activity in red gastrocnemius muscle while suppressing endogenous glucose production and lipolysis.
318	11334411	Because type 2 diabetes is characterized by diminished rates of insulin-stimulated glucose uptake as well as increased basal rates of endogenous glucose production and lipolysis, these results suggest that AICAR-related compounds may represent a new class of antidiabetic agents.
319	11352652	AMP-activated protein kinase (AMPK) may regulate a number of metabolic processes including glucose transport. 5-Aminoimidazole-4-carboxamideribonucleoside (AICAR), an AMPK activator, has been used to study the potential role of AMPK in rat skeletal muscle; however, its effects on glucose transport in mouse skeletal muscle are unknown.
320	11440910	Previous studies have shown that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a cell-permeable activator of AMP-activated protein kinase, increases the rate of fatty acid oxidation in skeletal muscle of fed rats.
321	11440910	In incubated soleus muscles isolated from fed rats, AICAR (2 mM) increased fatty acid oxidation (90%) and decreased ACC beta activity (40%) and malonyl-CoA concentration (50%); however, MCD activity was not significantly altered.
322	11440910	In soleus muscles from overnight-fasted rats, AICAR decreased ACC beta activity (40%), as it did in fed rats; however, it had no effect on the already high rate of fatty acid oxidation or the low malonyl-CoA concentration.
323	11440910	Surprisingly, AICAR did not significantly increase glucose uptake or assayable AMP-activated protein kinase activity in incubated soleus muscles from fed or fasted rats.
324	11440910	These results indicate that, in incubated rat soleus muscle, 1) AICAR does not activate MCD or stimulate glucose uptake as it does in extensor digitorum longus and epitrochlearis muscles, 2) the ability of AICAR to increase fatty acid oxidation and diminish glucose oxidation and malonyl-CoA concentration is dependent on the nutritional status of the rat, and 3) the ability of AICAR to diminish assayable ACC activity is independent of nutritional state.
325	11440910	Previous studies have shown that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a cell-permeable activator of AMP-activated protein kinase, increases the rate of fatty acid oxidation in skeletal muscle of fed rats.
326	11440910	In incubated soleus muscles isolated from fed rats, AICAR (2 mM) increased fatty acid oxidation (90%) and decreased ACC beta activity (40%) and malonyl-CoA concentration (50%); however, MCD activity was not significantly altered.
327	11440910	In soleus muscles from overnight-fasted rats, AICAR decreased ACC beta activity (40%), as it did in fed rats; however, it had no effect on the already high rate of fatty acid oxidation or the low malonyl-CoA concentration.
328	11440910	Surprisingly, AICAR did not significantly increase glucose uptake or assayable AMP-activated protein kinase activity in incubated soleus muscles from fed or fasted rats.
329	11440910	These results indicate that, in incubated rat soleus muscle, 1) AICAR does not activate MCD or stimulate glucose uptake as it does in extensor digitorum longus and epitrochlearis muscles, 2) the ability of AICAR to increase fatty acid oxidation and diminish glucose oxidation and malonyl-CoA concentration is dependent on the nutritional status of the rat, and 3) the ability of AICAR to diminish assayable ACC activity is independent of nutritional state.
330	11440910	Previous studies have shown that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a cell-permeable activator of AMP-activated protein kinase, increases the rate of fatty acid oxidation in skeletal muscle of fed rats.
331	11440910	In incubated soleus muscles isolated from fed rats, AICAR (2 mM) increased fatty acid oxidation (90%) and decreased ACC beta activity (40%) and malonyl-CoA concentration (50%); however, MCD activity was not significantly altered.
332	11440910	In soleus muscles from overnight-fasted rats, AICAR decreased ACC beta activity (40%), as it did in fed rats; however, it had no effect on the already high rate of fatty acid oxidation or the low malonyl-CoA concentration.
333	11440910	Surprisingly, AICAR did not significantly increase glucose uptake or assayable AMP-activated protein kinase activity in incubated soleus muscles from fed or fasted rats.
334	11440910	These results indicate that, in incubated rat soleus muscle, 1) AICAR does not activate MCD or stimulate glucose uptake as it does in extensor digitorum longus and epitrochlearis muscles, 2) the ability of AICAR to increase fatty acid oxidation and diminish glucose oxidation and malonyl-CoA concentration is dependent on the nutritional status of the rat, and 3) the ability of AICAR to diminish assayable ACC activity is independent of nutritional state.
335	11440910	Previous studies have shown that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a cell-permeable activator of AMP-activated protein kinase, increases the rate of fatty acid oxidation in skeletal muscle of fed rats.
336	11440910	In incubated soleus muscles isolated from fed rats, AICAR (2 mM) increased fatty acid oxidation (90%) and decreased ACC beta activity (40%) and malonyl-CoA concentration (50%); however, MCD activity was not significantly altered.
337	11440910	In soleus muscles from overnight-fasted rats, AICAR decreased ACC beta activity (40%), as it did in fed rats; however, it had no effect on the already high rate of fatty acid oxidation or the low malonyl-CoA concentration.
338	11440910	Surprisingly, AICAR did not significantly increase glucose uptake or assayable AMP-activated protein kinase activity in incubated soleus muscles from fed or fasted rats.
339	11440910	These results indicate that, in incubated rat soleus muscle, 1) AICAR does not activate MCD or stimulate glucose uptake as it does in extensor digitorum longus and epitrochlearis muscles, 2) the ability of AICAR to increase fatty acid oxidation and diminish glucose oxidation and malonyl-CoA concentration is dependent on the nutritional status of the rat, and 3) the ability of AICAR to diminish assayable ACC activity is independent of nutritional state.
340	11440910	Previous studies have shown that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a cell-permeable activator of AMP-activated protein kinase, increases the rate of fatty acid oxidation in skeletal muscle of fed rats.
341	11440910	In incubated soleus muscles isolated from fed rats, AICAR (2 mM) increased fatty acid oxidation (90%) and decreased ACC beta activity (40%) and malonyl-CoA concentration (50%); however, MCD activity was not significantly altered.
342	11440910	In soleus muscles from overnight-fasted rats, AICAR decreased ACC beta activity (40%), as it did in fed rats; however, it had no effect on the already high rate of fatty acid oxidation or the low malonyl-CoA concentration.
343	11440910	Surprisingly, AICAR did not significantly increase glucose uptake or assayable AMP-activated protein kinase activity in incubated soleus muscles from fed or fasted rats.
344	11440910	These results indicate that, in incubated rat soleus muscle, 1) AICAR does not activate MCD or stimulate glucose uptake as it does in extensor digitorum longus and epitrochlearis muscles, 2) the ability of AICAR to increase fatty acid oxidation and diminish glucose oxidation and malonyl-CoA concentration is dependent on the nutritional status of the rat, and 3) the ability of AICAR to diminish assayable ACC activity is independent of nutritional state.
345	11598104	5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside.
346	11598104	Activation of 5'-AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside (AICAR), exercise, or electrically stimulated contraction leads to increased glucose transport in skeletal muscle.
347	11598104	Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin-signaling cascade, insulin receptor substrate-1 (IRS-1).
348	11598104	We find that AMPK rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse C2C12 myotubes incubated with AICAR.
349	11598104	In the C2C12 myotubes activation of AMPK by AICAR matched the phosphorylation of IRS-1 on Ser-789.
350	11598104	This phosphorylation correlates with a 65% increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR.
351	11598104	The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR.
352	11598104	These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling.
353	11598104	5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside.
354	11598104	Activation of 5'-AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside (AICAR), exercise, or electrically stimulated contraction leads to increased glucose transport in skeletal muscle.
355	11598104	Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin-signaling cascade, insulin receptor substrate-1 (IRS-1).
356	11598104	We find that AMPK rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse C2C12 myotubes incubated with AICAR.
357	11598104	In the C2C12 myotubes activation of AMPK by AICAR matched the phosphorylation of IRS-1 on Ser-789.
358	11598104	This phosphorylation correlates with a 65% increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR.
359	11598104	The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR.
360	11598104	These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling.
361	11598104	5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside.
362	11598104	Activation of 5'-AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside (AICAR), exercise, or electrically stimulated contraction leads to increased glucose transport in skeletal muscle.
363	11598104	Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin-signaling cascade, insulin receptor substrate-1 (IRS-1).
364	11598104	We find that AMPK rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse C2C12 myotubes incubated with AICAR.
365	11598104	In the C2C12 myotubes activation of AMPK by AICAR matched the phosphorylation of IRS-1 on Ser-789.
366	11598104	This phosphorylation correlates with a 65% increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR.
367	11598104	The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR.
368	11598104	These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling.
369	11598104	5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside.
370	11598104	Activation of 5'-AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside (AICAR), exercise, or electrically stimulated contraction leads to increased glucose transport in skeletal muscle.
371	11598104	Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin-signaling cascade, insulin receptor substrate-1 (IRS-1).
372	11598104	We find that AMPK rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse C2C12 myotubes incubated with AICAR.
373	11598104	In the C2C12 myotubes activation of AMPK by AICAR matched the phosphorylation of IRS-1 on Ser-789.
374	11598104	This phosphorylation correlates with a 65% increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR.
375	11598104	The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR.
376	11598104	These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling.
377	11598104	5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside.
378	11598104	Activation of 5'-AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside (AICAR), exercise, or electrically stimulated contraction leads to increased glucose transport in skeletal muscle.
379	11598104	Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin-signaling cascade, insulin receptor substrate-1 (IRS-1).
380	11598104	We find that AMPK rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse C2C12 myotubes incubated with AICAR.
381	11598104	In the C2C12 myotubes activation of AMPK by AICAR matched the phosphorylation of IRS-1 on Ser-789.
382	11598104	This phosphorylation correlates with a 65% increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR.
383	11598104	The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR.
384	11598104	These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling.
385	11762693	Diabetes mellitus alters the vascular responsiveness to several vasoconstrictors and vasodilators. 5-amino-4-imidazole-carboxamide riboside (AICA-r), a nucleoside corresponding to AICA-ribotide and an intermediate of the de novo pathway of purine biosynthesis, was recently proposed as a new insulinotropic tool in non-insulin-dependent diabetes mellitus.
386	11872652	AMPK activity and glycogen metabolism were studied in red and white gastrocnemius muscles from rats treated with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) in vivo, and also in muscles incubated with AICAR in vitro.
387	11872652	AICAR increased muscle alpha2 AMPK activity, glycogen, and glucose-6-phosphate concentrations.
388	11872652	In vitro incubation with AICAR activated alpha2 AMPK but had no effect on either glycogen synthase or glycogen phosphorylase.
389	11872652	These results suggest that AICAR treatment does not promote glycogen accumulation in skeletal muscle in vivo by altering glycogen synthase and glycogen phosphorylase.
390	11872652	AMPK activity and glycogen metabolism were studied in red and white gastrocnemius muscles from rats treated with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) in vivo, and also in muscles incubated with AICAR in vitro.
391	11872652	AICAR increased muscle alpha2 AMPK activity, glycogen, and glucose-6-phosphate concentrations.
392	11872652	In vitro incubation with AICAR activated alpha2 AMPK but had no effect on either glycogen synthase or glycogen phosphorylase.
393	11872652	These results suggest that AICAR treatment does not promote glycogen accumulation in skeletal muscle in vivo by altering glycogen synthase and glycogen phosphorylase.
394	11872652	AMPK activity and glycogen metabolism were studied in red and white gastrocnemius muscles from rats treated with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) in vivo, and also in muscles incubated with AICAR in vitro.
395	11872652	AICAR increased muscle alpha2 AMPK activity, glycogen, and glucose-6-phosphate concentrations.
396	11872652	In vitro incubation with AICAR activated alpha2 AMPK but had no effect on either glycogen synthase or glycogen phosphorylase.
397	11872652	These results suggest that AICAR treatment does not promote glycogen accumulation in skeletal muscle in vivo by altering glycogen synthase and glycogen phosphorylase.
398	11872652	AMPK activity and glycogen metabolism were studied in red and white gastrocnemius muscles from rats treated with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) in vivo, and also in muscles incubated with AICAR in vitro.
399	11872652	AICAR increased muscle alpha2 AMPK activity, glycogen, and glucose-6-phosphate concentrations.
400	11872652	In vitro incubation with AICAR activated alpha2 AMPK but had no effect on either glycogen synthase or glycogen phosphorylase.
401	11872652	These results suggest that AICAR treatment does not promote glycogen accumulation in skeletal muscle in vivo by altering glycogen synthase and glycogen phosphorylase.
402	12061777	To investigate the effects of AMPK activation in animal models of type II diabetes, db/db and ob/ob mice were administered 5-aminoimidazole-4-carboxamide 1-beta-ribofuranoside (AICAR) subcutaneously either acutely (single injection) or twice per day for 8 days (chronic treatment).
403	12061777	Chronic AICAR administration also resulted in an elevation of total Glut4 concentration in skeletal muscle from ob/ob mice, but not db/db mice.
404	12061777	To investigate the effects of AMPK activation in animal models of type II diabetes, db/db and ob/ob mice were administered 5-aminoimidazole-4-carboxamide 1-beta-ribofuranoside (AICAR) subcutaneously either acutely (single injection) or twice per day for 8 days (chronic treatment).
405	12061777	Chronic AICAR administration also resulted in an elevation of total Glut4 concentration in skeletal muscle from ob/ob mice, but not db/db mice.
406	12086950	Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome.
407	12086950	Chronic chemical activation of AMP-activated protein kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) has been shown to augment insulin action, upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat.
408	12086950	To investigate whether chronic AICAR administration, in addition to the beneficial effects on insulin sensitivity, is capable of improving other phenotypes associated with the insulin resistance syndrome, obese Zucker (fa/fa) rats (n = 6) exhibiting insulin resistance, hyperlipidemia, and hypertension were subcutaneously injected with AICAR (0.5 mg/g body wt) daily for 7 weeks.
409	12086950	Furthermore, AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals.
410	12086950	Finally, in line with previous findings, AICAR treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles.
411	12086950	Our data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces systolic blood pressure in an insulin-resistant animal model.
412	12086950	The present study gives additional support to the hypothesis that AMPK activation might be a potential future pharmacological strategy for treating the insulin resistance syndrome.
413	12086950	Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome.
414	12086950	Chronic chemical activation of AMP-activated protein kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) has been shown to augment insulin action, upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat.
415	12086950	To investigate whether chronic AICAR administration, in addition to the beneficial effects on insulin sensitivity, is capable of improving other phenotypes associated with the insulin resistance syndrome, obese Zucker (fa/fa) rats (n = 6) exhibiting insulin resistance, hyperlipidemia, and hypertension were subcutaneously injected with AICAR (0.5 mg/g body wt) daily for 7 weeks.
416	12086950	Furthermore, AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals.
417	12086950	Finally, in line with previous findings, AICAR treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles.
418	12086950	Our data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces systolic blood pressure in an insulin-resistant animal model.
419	12086950	The present study gives additional support to the hypothesis that AMPK activation might be a potential future pharmacological strategy for treating the insulin resistance syndrome.
420	12086950	Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome.
421	12086950	Chronic chemical activation of AMP-activated protein kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) has been shown to augment insulin action, upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat.
422	12086950	To investigate whether chronic AICAR administration, in addition to the beneficial effects on insulin sensitivity, is capable of improving other phenotypes associated with the insulin resistance syndrome, obese Zucker (fa/fa) rats (n = 6) exhibiting insulin resistance, hyperlipidemia, and hypertension were subcutaneously injected with AICAR (0.5 mg/g body wt) daily for 7 weeks.
423	12086950	Furthermore, AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals.
424	12086950	Finally, in line with previous findings, AICAR treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles.
425	12086950	Our data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces systolic blood pressure in an insulin-resistant animal model.
426	12086950	The present study gives additional support to the hypothesis that AMPK activation might be a potential future pharmacological strategy for treating the insulin resistance syndrome.
427	12086950	Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome.
428	12086950	Chronic chemical activation of AMP-activated protein kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) has been shown to augment insulin action, upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat.
429	12086950	To investigate whether chronic AICAR administration, in addition to the beneficial effects on insulin sensitivity, is capable of improving other phenotypes associated with the insulin resistance syndrome, obese Zucker (fa/fa) rats (n = 6) exhibiting insulin resistance, hyperlipidemia, and hypertension were subcutaneously injected with AICAR (0.5 mg/g body wt) daily for 7 weeks.
430	12086950	Furthermore, AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals.
431	12086950	Finally, in line with previous findings, AICAR treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles.
432	12086950	Our data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces systolic blood pressure in an insulin-resistant animal model.
433	12086950	The present study gives additional support to the hypothesis that AMPK activation might be a potential future pharmacological strategy for treating the insulin resistance syndrome.
434	12086950	Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome.
435	12086950	Chronic chemical activation of AMP-activated protein kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) has been shown to augment insulin action, upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat.
436	12086950	To investigate whether chronic AICAR administration, in addition to the beneficial effects on insulin sensitivity, is capable of improving other phenotypes associated with the insulin resistance syndrome, obese Zucker (fa/fa) rats (n = 6) exhibiting insulin resistance, hyperlipidemia, and hypertension were subcutaneously injected with AICAR (0.5 mg/g body wt) daily for 7 weeks.
437	12086950	Furthermore, AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals.
438	12086950	Finally, in line with previous findings, AICAR treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles.
439	12086950	Our data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces systolic blood pressure in an insulin-resistant animal model.
440	12086950	The present study gives additional support to the hypothesis that AMPK activation might be a potential future pharmacological strategy for treating the insulin resistance syndrome.
441	12086950	Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome.
442	12086950	Chronic chemical activation of AMP-activated protein kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) has been shown to augment insulin action, upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat.
443	12086950	To investigate whether chronic AICAR administration, in addition to the beneficial effects on insulin sensitivity, is capable of improving other phenotypes associated with the insulin resistance syndrome, obese Zucker (fa/fa) rats (n = 6) exhibiting insulin resistance, hyperlipidemia, and hypertension were subcutaneously injected with AICAR (0.5 mg/g body wt) daily for 7 weeks.
444	12086950	Furthermore, AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals.
445	12086950	Finally, in line with previous findings, AICAR treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles.
446	12086950	Our data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces systolic blood pressure in an insulin-resistant animal model.
447	12086950	The present study gives additional support to the hypothesis that AMPK activation might be a potential future pharmacological strategy for treating the insulin resistance syndrome.
448	12351423	AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats.
449	12351423	As AMP-activated protein kinase (AMPK) plays an important role in muscle metabolism during exercise, we investigated the effects of the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) on insulin action in insulin-resistant high-fat-fed (HF) rats.
450	12351423	Thus, a single dose of AICAR leads to an apparent enhancement in whole-body, muscle, and liver insulin action in HF rats that extends beyond the expected time of AMPK activation.
451	12351423	Whether altered tissue lipid metabolism mediates AICAR effects on insulin action remains to be determined.
452	12351423	Independent of this, the results suggest that pharmacological activation of AMPK may have potential in treating insulin-resistant states and type 2 diabetes.
453	12351423	AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats.
454	12351423	As AMP-activated protein kinase (AMPK) plays an important role in muscle metabolism during exercise, we investigated the effects of the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) on insulin action in insulin-resistant high-fat-fed (HF) rats.
455	12351423	Thus, a single dose of AICAR leads to an apparent enhancement in whole-body, muscle, and liver insulin action in HF rats that extends beyond the expected time of AMPK activation.
456	12351423	Whether altered tissue lipid metabolism mediates AICAR effects on insulin action remains to be determined.
457	12351423	Independent of this, the results suggest that pharmacological activation of AMPK may have potential in treating insulin-resistant states and type 2 diabetes.
458	12351423	AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats.
459	12351423	As AMP-activated protein kinase (AMPK) plays an important role in muscle metabolism during exercise, we investigated the effects of the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) on insulin action in insulin-resistant high-fat-fed (HF) rats.
460	12351423	Thus, a single dose of AICAR leads to an apparent enhancement in whole-body, muscle, and liver insulin action in HF rats that extends beyond the expected time of AMPK activation.
461	12351423	Whether altered tissue lipid metabolism mediates AICAR effects on insulin action remains to be determined.
462	12351423	Independent of this, the results suggest that pharmacological activation of AMPK may have potential in treating insulin-resistant states and type 2 diabetes.
463	12351423	AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats.
464	12351423	As AMP-activated protein kinase (AMPK) plays an important role in muscle metabolism during exercise, we investigated the effects of the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) on insulin action in insulin-resistant high-fat-fed (HF) rats.
465	12351423	Thus, a single dose of AICAR leads to an apparent enhancement in whole-body, muscle, and liver insulin action in HF rats that extends beyond the expected time of AMPK activation.
466	12351423	Whether altered tissue lipid metabolism mediates AICAR effects on insulin action remains to be determined.
467	12351423	Independent of this, the results suggest that pharmacological activation of AMPK may have potential in treating insulin-resistant states and type 2 diabetes.
468	12376323	We examined whether acute activation of 5'-AMP-activated protein kinase (AMPK) by 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) ameliorates insulin resistance in isolated rat skeletal muscle.
469	12376323	When including 2 mM AICAR in the last hour of the 5-h incubation with palmitate, the inhibitory effect of palmitate on insulin-stimulated glycogen synthesis and glucose transport was eliminated.
470	12376323	This effect of AICAR was accompanied by activation of AMPK.
471	12376323	No effect of AICAR on the inhibited insulin-stimulated GS activity or increased GS phosphorylation by palmitate could be detected.
472	12376323	Thus the mechanism by which AMPK activation ameliorates the lipid-induced insulin resistance probably involves induction of compensatory mechanisms overriding the insulin resistance.
473	12376323	Our results emphasize AMPK as a promising molecular target for treatment of insulin resistance.
474	12376323	We examined whether acute activation of 5'-AMP-activated protein kinase (AMPK) by 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) ameliorates insulin resistance in isolated rat skeletal muscle.
475	12376323	When including 2 mM AICAR in the last hour of the 5-h incubation with palmitate, the inhibitory effect of palmitate on insulin-stimulated glycogen synthesis and glucose transport was eliminated.
476	12376323	This effect of AICAR was accompanied by activation of AMPK.
477	12376323	No effect of AICAR on the inhibited insulin-stimulated GS activity or increased GS phosphorylation by palmitate could be detected.
478	12376323	Thus the mechanism by which AMPK activation ameliorates the lipid-induced insulin resistance probably involves induction of compensatory mechanisms overriding the insulin resistance.
479	12376323	Our results emphasize AMPK as a promising molecular target for treatment of insulin resistance.
480	12376323	We examined whether acute activation of 5'-AMP-activated protein kinase (AMPK) by 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) ameliorates insulin resistance in isolated rat skeletal muscle.
481	12376323	When including 2 mM AICAR in the last hour of the 5-h incubation with palmitate, the inhibitory effect of palmitate on insulin-stimulated glycogen synthesis and glucose transport was eliminated.
482	12376323	This effect of AICAR was accompanied by activation of AMPK.
483	12376323	No effect of AICAR on the inhibited insulin-stimulated GS activity or increased GS phosphorylation by palmitate could be detected.
484	12376323	Thus the mechanism by which AMPK activation ameliorates the lipid-induced insulin resistance probably involves induction of compensatory mechanisms overriding the insulin resistance.
485	12376323	Our results emphasize AMPK as a promising molecular target for treatment of insulin resistance.
486	12376323	We examined whether acute activation of 5'-AMP-activated protein kinase (AMPK) by 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) ameliorates insulin resistance in isolated rat skeletal muscle.
487	12376323	When including 2 mM AICAR in the last hour of the 5-h incubation with palmitate, the inhibitory effect of palmitate on insulin-stimulated glycogen synthesis and glucose transport was eliminated.
488	12376323	This effect of AICAR was accompanied by activation of AMPK.
489	12376323	No effect of AICAR on the inhibited insulin-stimulated GS activity or increased GS phosphorylation by palmitate could be detected.
490	12376323	Thus the mechanism by which AMPK activation ameliorates the lipid-induced insulin resistance probably involves induction of compensatory mechanisms overriding the insulin resistance.
491	12376323	Our results emphasize AMPK as a promising molecular target for treatment of insulin resistance.
492	12376337	To determine whether intraislet hyperinsulinemia plays a role in the genesis of this defect, glucagon-secretory responses to moderate hypoglycemia induced by either insulin or a novel combination of the noninsulin glucose-lowering agents 5-aminoimidazole-4-carboxamide (AICAR) and phlorizin were compared in diabetic BB rats (an animal model of type 1 diabetes) and nondiabetic BB rats.
493	12376337	Combining phlorizin, AICAR, and insulin attenuated the glucagon response to hypoglycemia by 70% in the diabetic BB rat.
494	12376337	To determine whether intraislet hyperinsulinemia plays a role in the genesis of this defect, glucagon-secretory responses to moderate hypoglycemia induced by either insulin or a novel combination of the noninsulin glucose-lowering agents 5-aminoimidazole-4-carboxamide (AICAR) and phlorizin were compared in diabetic BB rats (an animal model of type 1 diabetes) and nondiabetic BB rats.
495	12376337	Combining phlorizin, AICAR, and insulin attenuated the glucagon response to hypoglycemia by 70% in the diabetic BB rat.
496	12476786	In skeletal muscle, activation of AMPK leads to increased glucose uptake, enhanced insulin sensitivity and oxidation of fatty acids.
497	12476786	Studies done in animal models of type 2 diabetes have shown that pharmacological activation of AMPK with the compound 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) decreases blood glucose and insulin concentrations.
498	12496137	Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles.
499	12496137	Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression.
500	12496137	AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions.
501	12496137	Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner.
502	12496137	In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.
503	12496137	Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles.
504	12496137	Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression.
505	12496137	AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions.
506	12496137	Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner.
507	12496137	In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.
508	12496137	Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles.
509	12496137	Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression.
510	12496137	AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions.
511	12496137	Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner.
512	12496137	In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.
513	12496137	Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles.
514	12496137	Physical activity is known to increase insulin action in skeletal muscle, and data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) can be used as a pharmacological tool to repetitively activate AMPK, and the objective of this study was to explore whether the increase in insulin-stimulated glucose uptake after either long-term exercise or chronic AICAR administration was followed by fiber-type-specific changes in insulin signaling and/or changes in GLUT-4 expression.
515	12496137	AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT-4 expression were determined in muscles characterized by different fiber type compositions.
516	12496137	Insulin signaling as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced only after AICAR administration and in a non-fiber-type-specific manner.
517	12496137	In conclusion, chronic AICAR administration and long-term exercise both improve insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific way, and this is associated with an increase in GLUT-4 content.
518	12502487	Inclusion of the glycogen phosphorylase inhibitor, CP-91149, prevented the loss of glycogen during glucose deprivation but not the activation of AMPK.
519	12502487	Activation of AMPK by either 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR) or hydrogen peroxide was also associated with a decrease in the activity ratio of GS.
520	12716734	AMP-activated protein kinase (AMPK) activation by AICAR (5-amino-imidazole carboxamide riboside) is correlated with increased glucose transport in rodent skeletal muscle via an insulin-independent pathway.
521	12716734	We determined in vitro effects of insulin and/or AICAR exposure on glucose transport and cell-surface GLUT4 content in skeletal muscle from nondiabetic men and men with type 2 diabetes.
522	12716734	Insulin and AICAR increased glucose transport and cell-surface GLUT4 content to a similar extent in control subjects.
523	12716734	In contrast, insulin- and AICAR-stimulated responses on glucose transport and cell-surface GLUT4 content were impaired in subjects with type 2 diabetes.
524	12716734	Importantly, exposure of type 2 diabetic skeletal muscle to a combination of insulin and AICAR increased glucose transport and cell-surface GLUT4 content to levels achieved in control subjects.
525	12716734	AICAR increased AMPK and acetyl-CoA carboxylase phosphorylation to a similar extent in skeletal muscle from subjects with type 2 diabetes and nondiabetic subjects.
526	12716734	Our studies highlight the potential importance of AMPK-dependent pathways in the regulation of GLUT4 and glucose transport activity in insulin-resistant skeletal muscle.
527	12716734	Activation of AMPK is an attractive strategy to enhance glucose transport through increased cell surface GLUT4 content in insulin-resistant skeletal muscle.
528	12829625	Contraction-induced fatty acid translocase/CD36 translocation in rat cardiac myocytes is mediated through AMP-activated protein kinase signaling.
529	12829625	Contraction of rat cardiac myocytes induces translocation of fatty acid translocase (FAT)/CD36 and GLUT4 from intracellular stores to the sarcolemma, leading to enhanced rates of long-chain fatty acid (FA) and glucose uptake, respectively.
530	12829625	Because intracellular AMP/ATP is elevated in contracting cardiac myocytes, we investigated whether activation of AMP-activated protein kinase (AMP kinase) is involved in contraction-inducible FAT/CD36 translocation.
531	12829625	Furthermore, the stimulating effects of both AICAR and oligomycin were antagonized by blocking FAT/CD36 with sulfo-N-succinimidylpalmitate, but not by inhibiting phosphatidylinositol 3-kinase with wortmannin, indicating the involvement of FAT/CD36, but excluding a role for insulin signaling.
532	12855688	Requirement for 3-phosphoinositide-kependent dinase-1 (PDK-1) in insulin-induced glucose uptake in immortalized brown adipocytes.
533	12855688	To provide insight into the physiological importance of 3-phosphoinositide-dependent kinase-1 (PDK-1) in the metabolic actions of insulin, we have generated mice that harbor a PDK-1 gene containing LoxP sites (PDK-1(lox/lox) mice) and established immortalized brown preadipocyte cell lines both from these animals and from wild-type mice.
534	12855688	In Cre-expressing PDK-1(lox/lox) adipocytes in which the abundance of PDK-1 was reduced by approximately 85%, the insulin-induced phosphorylation both of Akt on threonine 308 and of p70 S6 kinase on threonine-389 was markedly inhibited.
535	12855688	The phosphorylation both of Akt on serine 473 and of p42 and p44 isoforms of mitogen-activated protein kinase induced by insulin was not affected by Cre expression, indicating that the latter specifically inhibits PDK-1-dependent signaling.
536	12855688	Both glucose uptake and the translocation of glucose transporter 4 to the plasma membrane induced by insulin as well as glucose uptake induced by a constitutively active form of phosphoinositide 3-kinase were also greatly inhibited by Cre expression in PDK-1(lox/lox) adipocytes.
537	12855688	Phosphorylation of AMP-activated protein kinase and glucose uptake induced by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) were not affected by Cre expression in PDK-1(lox/lox) adipocytes.
538	12855688	These results indicate that PDK-1 is essential for insulin-induced glucose uptake in adipocytes.
539	12864738	AMPK can also be pharmacologically activated by the compound 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the antidiabetic agent metformin.
540	12864738	In isolated rat muscles, activation of AMPK is associated with increases in glucose uptake through an insulin-independent mechanism.
541	12864738	Studies done in rodents have shown that the activation of AMPK by AICAR is accompanied by decreases in blood glucose concentrations, in part due to enhanced muscle glucose uptake.
542	12864738	Similar to exercise, AICAR not only directly stimulates glucose uptake into the skeletal muscle, but also enhances insulin sensitivity.
543	12864738	AMPK can also be pharmacologically activated by the compound 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the antidiabetic agent metformin.
544	12864738	In isolated rat muscles, activation of AMPK is associated with increases in glucose uptake through an insulin-independent mechanism.
545	12864738	Studies done in rodents have shown that the activation of AMPK by AICAR is accompanied by decreases in blood glucose concentrations, in part due to enhanced muscle glucose uptake.
546	12864738	Similar to exercise, AICAR not only directly stimulates glucose uptake into the skeletal muscle, but also enhances insulin sensitivity.
547	12864738	AMPK can also be pharmacologically activated by the compound 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the antidiabetic agent metformin.
548	12864738	In isolated rat muscles, activation of AMPK is associated with increases in glucose uptake through an insulin-independent mechanism.
549	12864738	Studies done in rodents have shown that the activation of AMPK by AICAR is accompanied by decreases in blood glucose concentrations, in part due to enhanced muscle glucose uptake.
550	12864738	Similar to exercise, AICAR not only directly stimulates glucose uptake into the skeletal muscle, but also enhances insulin sensitivity.
551	13678417	Glucose 6-P levels were modulated in hepatocytes by glucokinase overexpression or inhibition with 5-thioglucose and the effects of AMP were tested using AICAR (5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside), which is metabolized to an AMP analogue.
552	14500570	Thus, factors that activate AMPK and decrease the concentration of malonyl CoA in peripheral tissues, such as exercise, decrease triglyceride accumulation in the adipocyte and other cells.
553	14500570	It also increases the expression of uncoupling proteins and the transcriptional regulator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha), which could possibly increase energy expenditure.
554	14500570	Recent studies suggest that the ability of leptin, adiponectin, 5'-aminoimidazole 4-carboxamide riboside (AICAR), adrenergic agonists, and metformin to diminish adiposity may be mediated, at least in part, by AMPK activation in peripheral tissues.
555	14690455	Over-expression of sterol-regulatory-element-binding protein-1c (SREBP1c) in rat pancreatic islets induces lipogenesis and decreases glucose-stimulated insulin release: modulation by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR).
556	14690455	In the present study, we determine whether over-expression in rat islets of the lipogenic transcription factor SREBP1c (sterol-regulatory-element-binding protein-1c) affects insulin release, and whether changes in islet lipid content may be reversed by activation of AMPK (AMP-activated protein kinase).
557	14690455	Real-time PCR (TaqMan) analysis showed that SREBP1c up-regulated the expression of FAS (fatty acid synthase; 6-fold), acetyl-CoA carboxylase-1 (2-fold), as well as peroxisomal-proliferator-activated receptor-gamma (7-fold), uncoupling protein-2 (1.4-fold) and Bcl2 (B-cell lymphocytic-leukaemia proto-oncogene 2; 1.3-fold).
558	14690455	By contrast, levels of pre-proinsulin, pancreatic duodenal homeobox-1, glucokinase and GLUT2 (glucose transporter isoform-2) mRNAs were unaltered.
559	14690455	Culture of islets with the AMPK activator 5-amino-4-imidazolecarboxamide riboside decreased the expression of the endogenous SREBP1c and FAS genes, and reversed the effect of over-expressing active SREBP1c on FAS mRNA levels and cellular triacylglycerol content.
560	14747282	Activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) also resulted in an approximate threefold increase in glucose transport in the epitrochlearis.
561	15068958	Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.
562	15068958	We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
563	15068958	We have also reported that LKB1 activates 11 other AMPK-related kinases.
564	15068958	The activity of LKB1 or the AMPK-related kinases has not previously been studied in a tissue with physiological relevance to diabetes.
565	15068958	In this study, we have investigated whether contraction, phenformin, and AICAR influence LKB1 and AMPK-related kinase activity in rat skeletal muscle.
566	15068958	Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity.
567	15068958	Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle.
568	15068958	The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1.
569	15068958	They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.
570	15068958	Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.
571	15068958	We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
572	15068958	We have also reported that LKB1 activates 11 other AMPK-related kinases.
573	15068958	The activity of LKB1 or the AMPK-related kinases has not previously been studied in a tissue with physiological relevance to diabetes.
574	15068958	In this study, we have investigated whether contraction, phenformin, and AICAR influence LKB1 and AMPK-related kinase activity in rat skeletal muscle.
575	15068958	Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity.
576	15068958	Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle.
577	15068958	The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1.
578	15068958	They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.
579	15068958	Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.
580	15068958	We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
581	15068958	We have also reported that LKB1 activates 11 other AMPK-related kinases.
582	15068958	The activity of LKB1 or the AMPK-related kinases has not previously been studied in a tissue with physiological relevance to diabetes.
583	15068958	In this study, we have investigated whether contraction, phenformin, and AICAR influence LKB1 and AMPK-related kinase activity in rat skeletal muscle.
584	15068958	Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity.
585	15068958	Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle.
586	15068958	The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1.
587	15068958	They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.
588	15068958	Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.
589	15068958	We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
590	15068958	We have also reported that LKB1 activates 11 other AMPK-related kinases.
591	15068958	The activity of LKB1 or the AMPK-related kinases has not previously been studied in a tissue with physiological relevance to diabetes.
592	15068958	In this study, we have investigated whether contraction, phenformin, and AICAR influence LKB1 and AMPK-related kinase activity in rat skeletal muscle.
593	15068958	Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity.
594	15068958	Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle.
595	15068958	The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1.
596	15068958	They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.
597	15068958	Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.
598	15068958	We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
599	15068958	We have also reported that LKB1 activates 11 other AMPK-related kinases.
600	15068958	The activity of LKB1 or the AMPK-related kinases has not previously been studied in a tissue with physiological relevance to diabetes.
601	15068958	In this study, we have investigated whether contraction, phenformin, and AICAR influence LKB1 and AMPK-related kinase activity in rat skeletal muscle.
602	15068958	Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity.
603	15068958	Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle.
604	15068958	The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1.
605	15068958	They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.
606	15068958	Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.
607	15068958	We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
608	15068958	We have also reported that LKB1 activates 11 other AMPK-related kinases.
609	15068958	The activity of LKB1 or the AMPK-related kinases has not previously been studied in a tissue with physiological relevance to diabetes.
610	15068958	In this study, we have investigated whether contraction, phenformin, and AICAR influence LKB1 and AMPK-related kinase activity in rat skeletal muscle.
611	15068958	Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity.
612	15068958	Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle.
613	15068958	The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1.
614	15068958	They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.
615	15068958	Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.
616	15068958	We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
617	15068958	We have also reported that LKB1 activates 11 other AMPK-related kinases.
618	15068958	The activity of LKB1 or the AMPK-related kinases has not previously been studied in a tissue with physiological relevance to diabetes.
619	15068958	In this study, we have investigated whether contraction, phenformin, and AICAR influence LKB1 and AMPK-related kinase activity in rat skeletal muscle.
620	15068958	Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity.
621	15068958	Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle.
622	15068958	The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1.
623	15068958	They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.
624	15220186	AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo.
625	15220186	Insulin-stimulated glucose uptake is increased in white but not red muscle of insulin-resistant high-fat-fed (HF) rats after administration of the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
626	15220186	AICAR decreased plasma levels of glucose (approximately 25%), insulin (approximately 60%), and FAs (approximately 30%) at various times over the next 46 min (P < 0.05 vs. controls).
627	15220186	We conclude that both glucose and FA fluxes are enhanced by AICAR more in white versus red muscle, consistent with the relative degree of activation of AMPK.
628	15220186	Therefore, a lesser effect of AICAR to alleviate muscle insulin resistance in red versus white muscle is not explained by a relatively greater effect on FA uptake in the red muscle.
629	15220186	AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo.
630	15220186	Insulin-stimulated glucose uptake is increased in white but not red muscle of insulin-resistant high-fat-fed (HF) rats after administration of the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
631	15220186	AICAR decreased plasma levels of glucose (approximately 25%), insulin (approximately 60%), and FAs (approximately 30%) at various times over the next 46 min (P < 0.05 vs. controls).
632	15220186	We conclude that both glucose and FA fluxes are enhanced by AICAR more in white versus red muscle, consistent with the relative degree of activation of AMPK.
633	15220186	Therefore, a lesser effect of AICAR to alleviate muscle insulin resistance in red versus white muscle is not explained by a relatively greater effect on FA uptake in the red muscle.
634	15220186	AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo.
635	15220186	Insulin-stimulated glucose uptake is increased in white but not red muscle of insulin-resistant high-fat-fed (HF) rats after administration of the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
636	15220186	AICAR decreased plasma levels of glucose (approximately 25%), insulin (approximately 60%), and FAs (approximately 30%) at various times over the next 46 min (P < 0.05 vs. controls).
637	15220186	We conclude that both glucose and FA fluxes are enhanced by AICAR more in white versus red muscle, consistent with the relative degree of activation of AMPK.
638	15220186	Therefore, a lesser effect of AICAR to alleviate muscle insulin resistance in red versus white muscle is not explained by a relatively greater effect on FA uptake in the red muscle.
639	15220186	AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo.
640	15220186	Insulin-stimulated glucose uptake is increased in white but not red muscle of insulin-resistant high-fat-fed (HF) rats after administration of the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
641	15220186	AICAR decreased plasma levels of glucose (approximately 25%), insulin (approximately 60%), and FAs (approximately 30%) at various times over the next 46 min (P < 0.05 vs. controls).
642	15220186	We conclude that both glucose and FA fluxes are enhanced by AICAR more in white versus red muscle, consistent with the relative degree of activation of AMPK.
643	15220186	Therefore, a lesser effect of AICAR to alleviate muscle insulin resistance in red versus white muscle is not explained by a relatively greater effect on FA uptake in the red muscle.
644	15220186	AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo.
645	15220186	Insulin-stimulated glucose uptake is increased in white but not red muscle of insulin-resistant high-fat-fed (HF) rats after administration of the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
646	15220186	AICAR decreased plasma levels of glucose (approximately 25%), insulin (approximately 60%), and FAs (approximately 30%) at various times over the next 46 min (P < 0.05 vs. controls).
647	15220186	We conclude that both glucose and FA fluxes are enhanced by AICAR more in white versus red muscle, consistent with the relative degree of activation of AMPK.
648	15220186	Therefore, a lesser effect of AICAR to alleviate muscle insulin resistance in red versus white muscle is not explained by a relatively greater effect on FA uptake in the red muscle.
649	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.
650	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.
651	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.
652	15235328	Hypoxia and AICAR increase glucose transport via an insulin-independent mechanism involving activation of 5'-AMP-activated kinase (AMPK).
653	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.
654	15235328	Our studies highlight important AMPK-dependent and independent pathways in the regulation of GLUT4 and glucose transport activity in insulin resistant skeletal muscle.
655	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.
656	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.
657	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.
658	15235328	Hypoxia and AICAR increase glucose transport via an insulin-independent mechanism involving activation of 5'-AMP-activated kinase (AMPK).
659	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.
660	15235328	Our studies highlight important AMPK-dependent and independent pathways in the regulation of GLUT4 and glucose transport activity in insulin resistant skeletal muscle.
661	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.
662	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.
663	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.
664	15235328	Hypoxia and AICAR increase glucose transport via an insulin-independent mechanism involving activation of 5'-AMP-activated kinase (AMPK).
665	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.
666	15235328	Our studies highlight important AMPK-dependent and independent pathways in the regulation of GLUT4 and glucose transport activity in insulin resistant skeletal muscle.
667	15277372	The additional chemical activation by AICAR of AMPK in the VMH during hypoglycemia markedly reduced the amount of exogenous glucose required to maintain plasma glucose during hypoglycemia, an effect that was almost completely accounted for by a three- to fourfold increase in hepatic glucose production in comparison to controls.
668	15277372	The combination of hypoglycemia- and AICAR-induced AMPK activity appears to result in a marked stimulus to hepatic glucose counterregulation.
669	15277372	The additional chemical activation by AICAR of AMPK in the VMH during hypoglycemia markedly reduced the amount of exogenous glucose required to maintain plasma glucose during hypoglycemia, an effect that was almost completely accounted for by a three- to fourfold increase in hepatic glucose production in comparison to controls.
670	15277372	The combination of hypoglycemia- and AICAR-induced AMPK activity appears to result in a marked stimulus to hepatic glucose counterregulation.
671	15356065	Obesity in humans is associated with lipid accumulation in skeletal muscle, insulin and leptin resistance, and type 2 diabetes.
672	15356065	To address the hypothesis that lipid accumulation in skeletal muscle of obese subjects may be due to down-regulation of AMPK, we measured mRNA and protein levels of AMPK isoforms, AMPKalpha1 and -alpha2 activity, AMPK kinase activity, acetyl-coenzyme A carboxylase (ACCbeta) expression and phosphorylation, and FA metabolism in biopsies of rectus abdominus muscle from lean and obese women.
673	15356065	We also examined the effect of 5-aminoimidazole-4-carboxamide riboside (AICAR) on AMPK activity and the effects of AICAR and leptin on FA metabolism.
674	15356065	However, AMPK mRNA and protein expression, AMPKalpha1 and -alpha2 activities, AMPK kinase activity, ACCbeta phosphorylation, and FA oxidation were similar in lean and obese subjects.
675	15356065	Moreover, AICAR increased AMPKalpha2 activity, ACCbeta phosphorylation, and palmitate oxidation to a similar degree in muscle from lean and obese subjects.
676	15356065	We conclude that the abnormal lipid metabolism and leptin resistance of skeletal muscle of obese subjects is not due to down-regulation of AMPK.
677	15356065	In addition, the similar stimulation by AICAR of AMPK in skeletal muscle of lean and obese subjects suggests that direct pharmacological activation of AMPK may be a therapeutic approach for stimulating FA oxidation in the treatment of human obesity.
678	15356065	Obesity in humans is associated with lipid accumulation in skeletal muscle, insulin and leptin resistance, and type 2 diabetes.
679	15356065	To address the hypothesis that lipid accumulation in skeletal muscle of obese subjects may be due to down-regulation of AMPK, we measured mRNA and protein levels of AMPK isoforms, AMPKalpha1 and -alpha2 activity, AMPK kinase activity, acetyl-coenzyme A carboxylase (ACCbeta) expression and phosphorylation, and FA metabolism in biopsies of rectus abdominus muscle from lean and obese women.
680	15356065	We also examined the effect of 5-aminoimidazole-4-carboxamide riboside (AICAR) on AMPK activity and the effects of AICAR and leptin on FA metabolism.
681	15356065	However, AMPK mRNA and protein expression, AMPKalpha1 and -alpha2 activities, AMPK kinase activity, ACCbeta phosphorylation, and FA oxidation were similar in lean and obese subjects.
682	15356065	Moreover, AICAR increased AMPKalpha2 activity, ACCbeta phosphorylation, and palmitate oxidation to a similar degree in muscle from lean and obese subjects.
683	15356065	We conclude that the abnormal lipid metabolism and leptin resistance of skeletal muscle of obese subjects is not due to down-regulation of AMPK.
684	15356065	In addition, the similar stimulation by AICAR of AMPK in skeletal muscle of lean and obese subjects suggests that direct pharmacological activation of AMPK may be a therapeutic approach for stimulating FA oxidation in the treatment of human obesity.
685	15356065	Obesity in humans is associated with lipid accumulation in skeletal muscle, insulin and leptin resistance, and type 2 diabetes.
686	15356065	To address the hypothesis that lipid accumulation in skeletal muscle of obese subjects may be due to down-regulation of AMPK, we measured mRNA and protein levels of AMPK isoforms, AMPKalpha1 and -alpha2 activity, AMPK kinase activity, acetyl-coenzyme A carboxylase (ACCbeta) expression and phosphorylation, and FA metabolism in biopsies of rectus abdominus muscle from lean and obese women.
687	15356065	We also examined the effect of 5-aminoimidazole-4-carboxamide riboside (AICAR) on AMPK activity and the effects of AICAR and leptin on FA metabolism.
688	15356065	However, AMPK mRNA and protein expression, AMPKalpha1 and -alpha2 activities, AMPK kinase activity, ACCbeta phosphorylation, and FA oxidation were similar in lean and obese subjects.
689	15356065	Moreover, AICAR increased AMPKalpha2 activity, ACCbeta phosphorylation, and palmitate oxidation to a similar degree in muscle from lean and obese subjects.
690	15356065	We conclude that the abnormal lipid metabolism and leptin resistance of skeletal muscle of obese subjects is not due to down-regulation of AMPK.
691	15356065	In addition, the similar stimulation by AICAR of AMPK in skeletal muscle of lean and obese subjects suggests that direct pharmacological activation of AMPK may be a therapeutic approach for stimulating FA oxidation in the treatment of human obesity.
692	15358229	Inhibition of cell growth was observed when AMPK was activated by either 5-aminoimidazole-4-carboxamide riboside (AICAR) or the thiazolidinedione rosiglitazone.
693	15358229	In addition, AICAR inhibited two key enzymes involved in protein synthesis, mTOR and p70S6K, and blocked the ability of the androgen R1881 to increase cell growth and the expression of two enzymes for de novo fatty acid synthesis, acetyl CoA carboxylase and fatty acid synthase, in the LNCaP cells.
694	15358229	Inhibition of cell growth was observed when AMPK was activated by either 5-aminoimidazole-4-carboxamide riboside (AICAR) or the thiazolidinedione rosiglitazone.
695	15358229	In addition, AICAR inhibited two key enzymes involved in protein synthesis, mTOR and p70S6K, and blocked the ability of the androgen R1881 to increase cell growth and the expression of two enzymes for de novo fatty acid synthesis, acetyl CoA carboxylase and fatty acid synthase, in the LNCaP cells.
696	15383370	To assess whether IL-6 increases fat oxidation, L6 myotubes were treated with PBS (Control), IL-6, or AICAR, a compound known to increase lipid oxidation.
697	15383370	Both IL-6 and AICAR markedly increased (P < 0.05) oxidation of [(14)C]palmitate compared with Control.
698	15383370	To assess whether IL-6 increases fat oxidation, L6 myotubes were treated with PBS (Control), IL-6, or AICAR, a compound known to increase lipid oxidation.
699	15383370	Both IL-6 and AICAR markedly increased (P < 0.05) oxidation of [(14)C]palmitate compared with Control.
700	15504342	AMPK inhibits fatty acid-induced increases in NF-kappaB transactivation in cultured human umbilical vein endothelial cells.
701	15504342	We report here a novel role of AMPK, to prevent the activation of NF-kappaB in endothelial cells exposed to the fatty acid palmitate or the cytokine TNF-alpha.
702	15504342	Incubation of cultured human umbilical vein endothelial cells (HUVEC) with elevated levels of palmitate (0.4mM) increased NF-kappaB reporter gene expression by 2- to 4-fold within 8h and caused a 7-fold increase in VCAM-1 mRNA expression at 24h.
703	15504342	Similar increases in NF-kappaB activation and VCAM-1 expression were not observed in cells incubated with an elevated concentration of glucose (25mM).
704	15504342	The increases in NF-kappaB activation and VCAM-1 expression caused by palmitate were markedly inhibited by co-incubation with the AMPK activator AICAR and, where studied, by expression of a constitutively active AMPK.
705	15504342	Likewise, AMPK activation inhibited the increase in NF-kappaB reporter gene expression observed in HUVEC incubated with TNF-alpha.
706	15504342	The results suggest that AMPK inhibits the activation of NF-kappaB caused by both palmitate and TNF-alpha.
707	15504342	The mechanism responsible for this action, as well as its relevance to the reported anti-atherogenic actions of exercise, metformin, thiazolidinediones, and adiponectin, all of which have been shown to activate AMPK, remains to be determined.
708	15547141	To determine the role of AMP-activated protein kinase (AMPK) activation on the regulation of fatty acid (FA) uptake and oxidation, we perfused rat hindquarters with 6 mM glucose, 10 microU/ml insulin, 550 microM palmitate, and [14C]palmitate during rest (R) or electrical stimulation (ES), inducing low-intensity (0.1 Hz) muscle contraction either with or without 2 mM 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
709	15547141	AICAR treatment significantly increased total FA oxidation (P < 0.05) during both R (0.38 +/- 0.11 vs. 0.89 +/- 0.1 nmol x min(-1) x g(-1)) and ES (0.73 +/- 0.11 vs. 2.01 +/- 0.1 nmol x min(-1) x g(-1)), which was paralleled in both conditions by a significant increase and significant decrease in AMPK and acetyl-CoA carboxylase (ACC) activity, respectively (P < 0.05).
710	15547141	Low-intensity muscle contraction increased glucose uptake, FA uptake, and total FA oxidation (P < 0.05) despite no change in AMPK (950.5 +/- 35.9 vs. 1,067.7 +/- 58.8 nmol x min(-1) x g(-1)) or ACC (51.2 +/- 6.7 vs. 55.7 +/- 2.0 nmol x min(-1) x g(-1)) activity from R to ES (P > 0.05).
711	15547141	When contraction and AICAR treatment were combined, the AICAR-induced increase in AMPK activity (34%) did not account for the synergistic increase in FA oxidation (175%) observed under similar conditions.
712	15547141	To determine the role of AMP-activated protein kinase (AMPK) activation on the regulation of fatty acid (FA) uptake and oxidation, we perfused rat hindquarters with 6 mM glucose, 10 microU/ml insulin, 550 microM palmitate, and [14C]palmitate during rest (R) or electrical stimulation (ES), inducing low-intensity (0.1 Hz) muscle contraction either with or without 2 mM 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
713	15547141	AICAR treatment significantly increased total FA oxidation (P < 0.05) during both R (0.38 +/- 0.11 vs. 0.89 +/- 0.1 nmol x min(-1) x g(-1)) and ES (0.73 +/- 0.11 vs. 2.01 +/- 0.1 nmol x min(-1) x g(-1)), which was paralleled in both conditions by a significant increase and significant decrease in AMPK and acetyl-CoA carboxylase (ACC) activity, respectively (P < 0.05).
714	15547141	Low-intensity muscle contraction increased glucose uptake, FA uptake, and total FA oxidation (P < 0.05) despite no change in AMPK (950.5 +/- 35.9 vs. 1,067.7 +/- 58.8 nmol x min(-1) x g(-1)) or ACC (51.2 +/- 6.7 vs. 55.7 +/- 2.0 nmol x min(-1) x g(-1)) activity from R to ES (P > 0.05).
715	15547141	When contraction and AICAR treatment were combined, the AICAR-induced increase in AMPK activity (34%) did not account for the synergistic increase in FA oxidation (175%) observed under similar conditions.
716	15547141	To determine the role of AMP-activated protein kinase (AMPK) activation on the regulation of fatty acid (FA) uptake and oxidation, we perfused rat hindquarters with 6 mM glucose, 10 microU/ml insulin, 550 microM palmitate, and [14C]palmitate during rest (R) or electrical stimulation (ES), inducing low-intensity (0.1 Hz) muscle contraction either with or without 2 mM 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
717	15547141	AICAR treatment significantly increased total FA oxidation (P < 0.05) during both R (0.38 +/- 0.11 vs. 0.89 +/- 0.1 nmol x min(-1) x g(-1)) and ES (0.73 +/- 0.11 vs. 2.01 +/- 0.1 nmol x min(-1) x g(-1)), which was paralleled in both conditions by a significant increase and significant decrease in AMPK and acetyl-CoA carboxylase (ACC) activity, respectively (P < 0.05).
718	15547141	Low-intensity muscle contraction increased glucose uptake, FA uptake, and total FA oxidation (P < 0.05) despite no change in AMPK (950.5 +/- 35.9 vs. 1,067.7 +/- 58.8 nmol x min(-1) x g(-1)) or ACC (51.2 +/- 6.7 vs. 55.7 +/- 2.0 nmol x min(-1) x g(-1)) activity from R to ES (P > 0.05).
719	15547141	When contraction and AICAR treatment were combined, the AICAR-induced increase in AMPK activity (34%) did not account for the synergistic increase in FA oxidation (175%) observed under similar conditions.
720	15616009	Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity.
721	15616009	In 3T3-L1 adipocytes, insulin-stimulated GLUT4 translocation requires phosphorylation of the protein designated Akt substrate of 160 kDa (AS160).
722	15616009	Both insulin and contractions activate Akt in skeletal muscle.
723	15616009	Therefore, we assessed the effects in skeletal muscle of each stimulus on phosphorylation of proteins, including AS160, on the Akt phosphomotif.
724	15616009	Isolated rat epitrochlearis muscles were incubated with insulin (for time course and dose response), stimulated to contract, or incubated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) and used to assess the following: serine-phosphorylation of Akt (P-Akt), immunoreactivity with an antibody recognizing the Akt phosphomotif (alpha-phospho-[Ser/Thr] Akt substrate [PAS]), and PAS immunoreactivity of samples immunoprecipitated with anti-AS160.
725	15616009	Wortmannin inhibited insulin (120 nmol/l) and contraction effects on AS160 phosphorylation.
726	15616009	Incubation with AICAR caused increased phosphorylation of AMP-activated protein kinase and AS160 but not Akt.
727	15616009	Our working hypothesis is that phosphorylation of these putative Akt substrates is important for some of the insulin and contraction bioeffects.
728	15616009	Increased phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle in response to insulin or contractile activity.
729	15616009	In 3T3-L1 adipocytes, insulin-stimulated GLUT4 translocation requires phosphorylation of the protein designated Akt substrate of 160 kDa (AS160).
730	15616009	Both insulin and contractions activate Akt in skeletal muscle.
731	15616009	Therefore, we assessed the effects in skeletal muscle of each stimulus on phosphorylation of proteins, including AS160, on the Akt phosphomotif.
732	15616009	Isolated rat epitrochlearis muscles were incubated with insulin (for time course and dose response), stimulated to contract, or incubated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) and used to assess the following: serine-phosphorylation of Akt (P-Akt), immunoreactivity with an antibody recognizing the Akt phosphomotif (alpha-phospho-[Ser/Thr] Akt substrate [PAS]), and PAS immunoreactivity of samples immunoprecipitated with anti-AS160.
733	15616009	Wortmannin inhibited insulin (120 nmol/l) and contraction effects on AS160 phosphorylation.
734	15616009	Incubation with AICAR caused increased phosphorylation of AMP-activated protein kinase and AS160 but not Akt.
735	15616009	Our working hypothesis is that phosphorylation of these putative Akt substrates is important for some of the insulin and contraction bioeffects.
736	15677492	These data show that elevations in hepatic ZMP concentrations, induced by portal venous AICAR infusion, cause acute hepatic insulin resistance.
737	15793229	The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined.
738	15793229	Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01).
739	15793229	In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function.
740	15793229	Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.
741	15793229	The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined.
742	15793229	Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01).
743	15793229	In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function.
744	15793229	Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.
745	15793229	The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined.
746	15793229	Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01).
747	15793229	In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function.
748	15793229	Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.
749	15893773	Adiponectin-mediated stimulation of AMP-activated protein kinase (AMPK) in pancreatic beta cells.
750	15893773	The effects were ascribed to adiponectin-receptor mediated activation of the key metabolic regulator AMP-activated protein kinase (AMPK).
751	15893773	We therefore investigated a possible adiponectin-induced activation of AMPK in beta cells.
752	15893773	RT-PCR analysis confirmed the expression of adiponectin receptor subtypes 1 and 2 in rat beta cells and showed their expression in insulin-secreting MIN6 cells.
753	15893773	Culture with physiological concentrations (2.5 microg/ml) of globular adiponectin was found to increase the phosphorylation of both AMPK and acetylcoA carboxylase (ACC) in these cell types.
754	15893773	Like the pharmacological AMPK activator 5-amino-imidazole-4-carboxamide-riboside (AICAR), adiponectin activated AMPK in beta cells and MIN6 cells.
755	15893773	We conclude that adiponectin induces an activation of AMPK in beta cells, which inhibits their cataplerosis of glucose-carbon to lipids.
756	16039647	Metformin reduces adiponectin protein expression and release in 3T3-L1 adipocytes involving activation of AMP activated protein kinase.
757	16039647	Both compounds act through different mechanisms which might include opposing effects on the production of adiponectin, an insulin-sensitizer released by adipocytes.
758	16039647	Addition of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR) also caused a decrease in adiponectin protein expression.
759	16186119	Known AMPK stimuli including 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), rotenone (a Complex I inhibitor), dinitrophenol (a mitochondrial uncoupler), muscle contraction, and sorbitol (producing hyperosmolar shock) did not increase AMPK alpha2 activity in alpha2i TG mice, whereas alpha1 activation was attenuated by only 30-50%.
760	16186119	AICAR- and rotenone-stimulated glucose transport was fully inhibited in alpha2i TG mice; however, the lack of AMPK alpha2 activity had no effect on contraction- or sorbitol-induced glucose transport.
761	16186119	Thus, AMPK alpha2 activation is essential for some, but not all, insulin-independent glucose transport.
762	16186119	Known AMPK stimuli including 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), rotenone (a Complex I inhibitor), dinitrophenol (a mitochondrial uncoupler), muscle contraction, and sorbitol (producing hyperosmolar shock) did not increase AMPK alpha2 activity in alpha2i TG mice, whereas alpha1 activation was attenuated by only 30-50%.
763	16186119	AICAR- and rotenone-stimulated glucose transport was fully inhibited in alpha2i TG mice; however, the lack of AMPK alpha2 activity had no effect on contraction- or sorbitol-induced glucose transport.
764	16186119	Thus, AMPK alpha2 activation is essential for some, but not all, insulin-independent glucose transport.
765	16380484	Treatment with metformin and AICAR inhibited hyperglycemia-induced intracellular and mtROS production, stimulated AMP-activated protein kinase (AMPK) activity, and increased the expression of peroxisome proliferator-activated response-gamma coactivator-1alpha (PGC-1alpha) and manganese superoxide dismutase (MnSOD) mRNAs.
766	16380484	The dominant negative form of AMPKalpha1 diminished the effects of metformin and AICAR on these events, and an overexpression of PGC-1alpha completely blocked the hyperglycemia-induced mtROS production.
767	16380484	In addition, metformin and AICAR increased the mRNA expression of nuclear respiratory factor-1 and mitochondrial DNA transcription factor A (mtTFA) and stimulated the mitochondrial proliferation.
768	16380484	Treatment with metformin and AICAR inhibited hyperglycemia-induced intracellular and mtROS production, stimulated AMP-activated protein kinase (AMPK) activity, and increased the expression of peroxisome proliferator-activated response-gamma coactivator-1alpha (PGC-1alpha) and manganese superoxide dismutase (MnSOD) mRNAs.
769	16380484	The dominant negative form of AMPKalpha1 diminished the effects of metformin and AICAR on these events, and an overexpression of PGC-1alpha completely blocked the hyperglycemia-induced mtROS production.
770	16380484	In addition, metformin and AICAR increased the mRNA expression of nuclear respiratory factor-1 and mitochondrial DNA transcription factor A (mtTFA) and stimulated the mitochondrial proliferation.
771	16380484	Treatment with metformin and AICAR inhibited hyperglycemia-induced intracellular and mtROS production, stimulated AMP-activated protein kinase (AMPK) activity, and increased the expression of peroxisome proliferator-activated response-gamma coactivator-1alpha (PGC-1alpha) and manganese superoxide dismutase (MnSOD) mRNAs.
772	16380484	The dominant negative form of AMPKalpha1 diminished the effects of metformin and AICAR on these events, and an overexpression of PGC-1alpha completely blocked the hyperglycemia-induced mtROS production.
773	16380484	In addition, metformin and AICAR increased the mRNA expression of nuclear respiratory factor-1 and mitochondrial DNA transcription factor A (mtTFA) and stimulated the mitochondrial proliferation.
774	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.
775	16515522	Recent studies have shown that AMPK is the cellular mediator for many of the metabolic effects of drugs such as metformin and thiazolidinediones, as well as the insulin sensitizing adipocytokines leptin and adiponectin.
776	16515522	These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.
777	16563350	Cytokine secretion by human adipocytes is differentially regulated by adiponectin, AICAR, and troglitazone.
778	16563350	Secretion of IL-6, IL-8, MIP-1alpha/beta, and MCP-1 by adipocytes was found to be downregulated by adiponectin.
779	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.
780	16567505	5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation.
781	16567505	We report here that 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), metformin, and oligomycin activated AMPK and inhibited glucose phosphorylation and glycolysis in rat hepatocytes.
782	16567505	In vitro experiments demonstrated that this inhibition was not due to direct phosphorylation of glucokinase or its regulatory protein by AMPK.
783	16567505	By contrast, AMPK phosphorylated liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase without affecting activity.
784	16567505	Inhibitors of the endothelial nitric oxide synthase, stress kinases, and phosphatidylinositol 3-kinase pathways did not counteract the effects of AICAR, metformin, or oligomycin, suggesting that these signaling pathways were not involved.
785	16567505	Finally, AICAR, metformin, and oligomycin were found to inhibit the glucose-induced translocation of glucokinase from the nucleus to the cytosol by a mechanism that could be related to the decrease in intracellular ATP concentrations observed in these conditions.
786	16567505	5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation.
787	16567505	We report here that 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), metformin, and oligomycin activated AMPK and inhibited glucose phosphorylation and glycolysis in rat hepatocytes.
788	16567505	In vitro experiments demonstrated that this inhibition was not due to direct phosphorylation of glucokinase or its regulatory protein by AMPK.
789	16567505	By contrast, AMPK phosphorylated liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase without affecting activity.
790	16567505	Inhibitors of the endothelial nitric oxide synthase, stress kinases, and phosphatidylinositol 3-kinase pathways did not counteract the effects of AICAR, metformin, or oligomycin, suggesting that these signaling pathways were not involved.
791	16567505	Finally, AICAR, metformin, and oligomycin were found to inhibit the glucose-induced translocation of glucokinase from the nucleus to the cytosol by a mechanism that could be related to the decrease in intracellular ATP concentrations observed in these conditions.
792	16567505	5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation.
793	16567505	We report here that 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), metformin, and oligomycin activated AMPK and inhibited glucose phosphorylation and glycolysis in rat hepatocytes.
794	16567505	In vitro experiments demonstrated that this inhibition was not due to direct phosphorylation of glucokinase or its regulatory protein by AMPK.
795	16567505	By contrast, AMPK phosphorylated liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase without affecting activity.
796	16567505	Inhibitors of the endothelial nitric oxide synthase, stress kinases, and phosphatidylinositol 3-kinase pathways did not counteract the effects of AICAR, metformin, or oligomycin, suggesting that these signaling pathways were not involved.
797	16567505	Finally, AICAR, metformin, and oligomycin were found to inhibit the glucose-induced translocation of glucokinase from the nucleus to the cytosol by a mechanism that could be related to the decrease in intracellular ATP concentrations observed in these conditions.
798	16731839	Before the acute study, rats were microinjected to the VMH with either 5-aminoimidazole-4-carboxamide (AICAR; n=12), to activate AMPK, or saline (n=12).
799	16731851	Vascular signal transduction by adiponectin is poorly understood and may involve 5'-AMP-activated protein kinase (AMPK), cAMP signaling, and other pathways.
800	16731851	The AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 1 mmol/l, 16 h) only partially decreased glucose-induced ROS by 22% (P<0.05).
801	16731851	Incubation with the cAMP-dependent protein kinase (PKA) inhibitor H-89 (1 micromol/l) fully abrogated the effect of gAd, but not that of AICAR, on ROS induced by glucose. gAd also increased cellular cAMP content by 70% in an AMPK-independent manner.
802	16731851	Vascular signal transduction by adiponectin is poorly understood and may involve 5'-AMP-activated protein kinase (AMPK), cAMP signaling, and other pathways.
803	16731851	The AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 1 mmol/l, 16 h) only partially decreased glucose-induced ROS by 22% (P<0.05).
804	16731851	Incubation with the cAMP-dependent protein kinase (PKA) inhibitor H-89 (1 micromol/l) fully abrogated the effect of gAd, but not that of AICAR, on ROS induced by glucose. gAd also increased cellular cAMP content by 70% in an AMPK-independent manner.
805	16772328	AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA).
806	16772328	In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and R(d tissue) responses were markedly attenuated, but MCR(g) and GF increased significantly.
807	16772328	AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA).
808	16772328	In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and R(d tissue) responses were markedly attenuated, but MCR(g) and GF increased significantly.
809	16804075	AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.
810	16804075	AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR).
811	16804075	AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake.
812	16804075	We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle.
813	16804075	In mice deficient in AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle.
814	16804075	AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.
815	16804075	AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR).
816	16804075	AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake.
817	16804075	We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle.
818	16804075	In mice deficient in AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle.
819	16804075	AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.
820	16804075	AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR).
821	16804075	AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake.
822	16804075	We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle.
823	16804075	In mice deficient in AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle.
824	16804077	Insulin and contraction increase GLUT4 translocation in skeletal muscle via distinct signaling mechanisms.
825	16804077	Akt substrate of 160 kDa (AS160) mediates insulin-stimulated GLUT4 translocation in L6 myotubes, presumably through activation of Akt.
826	16804077	Using in vivo, in vitro, and in situ methods, insulin, contraction, and the AMP-activated protein kinase (AMPK) activator AICAR all increased AS160 phosphorylation in mouse skeletal muscle.
827	16804077	To determine if AMPK mediates AS160 signaling, we used AMPK alpha2-inactive (alpha2i) transgenic mice.
828	16804077	AICAR-stimulated AS160 phosphorylation was fully inhibited, whereas contraction-stimulated AS160 phosphorylation was partially reduced in the AMPK alpha2i transgenic mice.
829	16804077	Combined AMPK alpha2 and Akt inhibition by wortmannin treatment of AMPK alpha2 transgenic mice did not fully ablate contraction-stimulated AS160 phosphorylation.
830	16804077	While Akt and AMPK alpha2 activities are essential for AS160 phosphorylation by insulin and AICAR, respectively, neither kinase is indispensable for the entire effects of contraction on AS160 phosphorylation.
831	16804077	Insulin and contraction increase GLUT4 translocation in skeletal muscle via distinct signaling mechanisms.
832	16804077	Akt substrate of 160 kDa (AS160) mediates insulin-stimulated GLUT4 translocation in L6 myotubes, presumably through activation of Akt.
833	16804077	Using in vivo, in vitro, and in situ methods, insulin, contraction, and the AMP-activated protein kinase (AMPK) activator AICAR all increased AS160 phosphorylation in mouse skeletal muscle.
834	16804077	To determine if AMPK mediates AS160 signaling, we used AMPK alpha2-inactive (alpha2i) transgenic mice.
835	16804077	AICAR-stimulated AS160 phosphorylation was fully inhibited, whereas contraction-stimulated AS160 phosphorylation was partially reduced in the AMPK alpha2i transgenic mice.
836	16804077	Combined AMPK alpha2 and Akt inhibition by wortmannin treatment of AMPK alpha2 transgenic mice did not fully ablate contraction-stimulated AS160 phosphorylation.
837	16804077	While Akt and AMPK alpha2 activities are essential for AS160 phosphorylation by insulin and AICAR, respectively, neither kinase is indispensable for the entire effects of contraction on AS160 phosphorylation.
838	16816404	5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced AMP-activated protein kinase phosphorylation inhibits basal and insulin-stimulated glucose uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes.
839	16816404	The objective of this study was to investigate the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR)-induced AMP-activated protein kinase (AMPK) activation on basal and insulin-stimulated glucose and fatty acid metabolism in isolated rat adipocytes.
840	16816404	AICAR-induced AMPK activation profoundly inhibited basal and insulin-stimulated glucose uptake, lipogenesis, glucose oxidation, and lactate production in fat cells.
841	16816404	We also describe the novel findings that AICAR-induced AMPK phosphorylation significantly reduced palmitate (32%) and oleate uptake (41%), which was followed by a 50% reduction in palmitate oxidation despite a marked increase in AMPK and acetyl-CoA carboxylase phosphorylation.
842	16816404	Compound C, a selective inhibitor of AMPK, not only completely prevented the inhibitory effect of AICAR on palmitate oxidation but actually caused a 2.2-fold increase in this variable.
843	16816404	5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced AMP-activated protein kinase phosphorylation inhibits basal and insulin-stimulated glucose uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes.
844	16816404	The objective of this study was to investigate the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR)-induced AMP-activated protein kinase (AMPK) activation on basal and insulin-stimulated glucose and fatty acid metabolism in isolated rat adipocytes.
845	16816404	AICAR-induced AMPK activation profoundly inhibited basal and insulin-stimulated glucose uptake, lipogenesis, glucose oxidation, and lactate production in fat cells.
846	16816404	We also describe the novel findings that AICAR-induced AMPK phosphorylation significantly reduced palmitate (32%) and oleate uptake (41%), which was followed by a 50% reduction in palmitate oxidation despite a marked increase in AMPK and acetyl-CoA carboxylase phosphorylation.
847	16816404	Compound C, a selective inhibitor of AMPK, not only completely prevented the inhibitory effect of AICAR on palmitate oxidation but actually caused a 2.2-fold increase in this variable.
848	16816404	5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced AMP-activated protein kinase phosphorylation inhibits basal and insulin-stimulated glucose uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes.
849	16816404	The objective of this study was to investigate the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR)-induced AMP-activated protein kinase (AMPK) activation on basal and insulin-stimulated glucose and fatty acid metabolism in isolated rat adipocytes.
850	16816404	AICAR-induced AMPK activation profoundly inhibited basal and insulin-stimulated glucose uptake, lipogenesis, glucose oxidation, and lactate production in fat cells.
851	16816404	We also describe the novel findings that AICAR-induced AMPK phosphorylation significantly reduced palmitate (32%) and oleate uptake (41%), which was followed by a 50% reduction in palmitate oxidation despite a marked increase in AMPK and acetyl-CoA carboxylase phosphorylation.
852	16816404	Compound C, a selective inhibitor of AMPK, not only completely prevented the inhibitory effect of AICAR on palmitate oxidation but actually caused a 2.2-fold increase in this variable.
853	16816404	5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced AMP-activated protein kinase phosphorylation inhibits basal and insulin-stimulated glucose uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes.
854	16816404	The objective of this study was to investigate the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR)-induced AMP-activated protein kinase (AMPK) activation on basal and insulin-stimulated glucose and fatty acid metabolism in isolated rat adipocytes.
855	16816404	AICAR-induced AMPK activation profoundly inhibited basal and insulin-stimulated glucose uptake, lipogenesis, glucose oxidation, and lactate production in fat cells.
856	16816404	We also describe the novel findings that AICAR-induced AMPK phosphorylation significantly reduced palmitate (32%) and oleate uptake (41%), which was followed by a 50% reduction in palmitate oxidation despite a marked increase in AMPK and acetyl-CoA carboxylase phosphorylation.
857	16816404	Compound C, a selective inhibitor of AMPK, not only completely prevented the inhibitory effect of AICAR on palmitate oxidation but actually caused a 2.2-fold increase in this variable.
858	16822958	Although similar to the effects of insulin to increase glucose transport in muscle, it is clear that the underlying mechanisms for AMPK-mediated glucose transport involve proximal signals that are distinct from that of insulin.
859	16822958	We also discuss evidence that AMPK may play a role in enhancing muscle and whole body insulin sensitivity for glucose transport under conditions such as exercise, as well as the use of the AMPK activator AICAR to reverse insulin-resistant conditions.
860	16949049	Keratinocytes were incubated for 12 h with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
861	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.
862	16949049	Keratinocytes were incubated for 12 h with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR).
863	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.
864	17003345	AMP-activated protein kinase (AMPK) has been implicated in the insulin-sensitizing actions of thiazolidinediones (TZDs), but it is not known whether TZD treatment can enhance tissue glucose uptake in response to AMPK activation.
865	17003345	The present study investigated the influence of the TZD rosiglitazone on glucose turnover induced by intravenous infusion of the AMPK activator 5-aminoimidazole 4-carboxamide riboside (AICAR) under euglycemic and iso-insulinemic conditions in insulin-resistant high-fat-fed rats.
866	17003345	Thus, our findings suggest that in addition to ameliorating insulin resistance, TZDs may enhance AMPK-stimulated glucose clearance into peripheral tissues in insulin-resistant states.
867	17018841	These high-glucose-induced changes in protein synthesis were phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin (mTOR) dependent and transforming growth factor-beta independent.
868	17018841	High glucose reduced AMPK alpha-subunit theronine (Thr) 172 phosphorylation, which required Akt activation.
869	17018841	Metformin and 5-aminoimidazole-4-carboxamide-1beta-riboside (AICAR) increased AMPK phosphorylation, inhibited high-glucose stimulation of protein synthesis, and prevented high-glucose-induced changes in phosphorylation of 4E binding protein 1 and eukaryotic elongation factor 2.
870	17018841	In diabetic rats, metformin and AICAR increased renal AMPK phosphorylation, reversed mTOR activation, and inhibited renal hypertrophy, without affecting hyperglycemia.
871	17018841	These high-glucose-induced changes in protein synthesis were phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin (mTOR) dependent and transforming growth factor-beta independent.
872	17018841	High glucose reduced AMPK alpha-subunit theronine (Thr) 172 phosphorylation, which required Akt activation.
873	17018841	Metformin and 5-aminoimidazole-4-carboxamide-1beta-riboside (AICAR) increased AMPK phosphorylation, inhibited high-glucose stimulation of protein synthesis, and prevented high-glucose-induced changes in phosphorylation of 4E binding protein 1 and eukaryotic elongation factor 2.
874	17018841	In diabetic rats, metformin and AICAR increased renal AMPK phosphorylation, reversed mTOR activation, and inhibited renal hypertrophy, without affecting hyperglycemia.
875	17083919	LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
876	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.
877	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.
878	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.
879	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
880	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.
881	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.
882	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
883	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.
884	17083919	LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
885	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.
886	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.
887	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.
888	17083919	In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected.
889	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.
890	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.
891	17083919	The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells.
892	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.
893	17143782	In this study, we aimed to determine the alterations of beta-cell ultrastructure, insulin mRNA and protein products of the same gene on the pancreas of rats following long-term treatment of 5-aminoimidazole-4-carboxamide riboside (AICAR).
894	17143782	In the AICAR-treated group, numerous beta cells showed increased insulin gene expression.
895	17143782	As a result, it is suggested that AICAR may induce insulin synthesis and betacell regeneration in n2 STZ-diabetic rats.
896	17143782	In this study, we aimed to determine the alterations of beta-cell ultrastructure, insulin mRNA and protein products of the same gene on the pancreas of rats following long-term treatment of 5-aminoimidazole-4-carboxamide riboside (AICAR).
897	17143782	In the AICAR-treated group, numerous beta cells showed increased insulin gene expression.
898	17143782	As a result, it is suggested that AICAR may induce insulin synthesis and betacell regeneration in n2 STZ-diabetic rats.
899	17143782	In this study, we aimed to determine the alterations of beta-cell ultrastructure, insulin mRNA and protein products of the same gene on the pancreas of rats following long-term treatment of 5-aminoimidazole-4-carboxamide riboside (AICAR).
900	17143782	In the AICAR-treated group, numerous beta cells showed increased insulin gene expression.
901	17143782	As a result, it is suggested that AICAR may induce insulin synthesis and betacell regeneration in n2 STZ-diabetic rats.
902	17170237	Glucose, insulin, and leptin signaling pathways modulate nitric oxide synthesis in glucose-inhibited neurons in the ventromedial hypothalamus.
903	17170237	Thus this study tests the hypothesis that NO synthesis is a site of convergence for glucose, leptin, and insulin signaling in VMH glucose-sensing neurons.
904	17170237	With the use of the NO-sensitive dye 4-amino-5-methylamino-2',7'-difluorofluorescein in conjunction with the membrane potential-sensitive dye fluorometric imaging plate reader, we found that glucose and leptin suppress, whereas insulin stimulates neuronal nitric oxide synthase (nNOS)-dependent NO production in cultured VMH GI neurons.
905	17170237	The effects of glucose and leptin were mediated by suppression of AMP-activated protein kinase (AMPK).
906	17170237	The AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) increased both NO production and neuronal activity in GI neurons.
907	17170237	Furthermore, decreased glucose, insulin, and AICAR increase the phosphorylation of VMH nNOS, whereas leptin decreases it.
908	17170237	Thus NO may mediate, in part, glucose, leptin, and insulin signaling in VMH glucose-sensing neurons.
909	17170237	Glucose, insulin, and leptin signaling pathways modulate nitric oxide synthesis in glucose-inhibited neurons in the ventromedial hypothalamus.
910	17170237	Thus this study tests the hypothesis that NO synthesis is a site of convergence for glucose, leptin, and insulin signaling in VMH glucose-sensing neurons.
911	17170237	With the use of the NO-sensitive dye 4-amino-5-methylamino-2',7'-difluorofluorescein in conjunction with the membrane potential-sensitive dye fluorometric imaging plate reader, we found that glucose and leptin suppress, whereas insulin stimulates neuronal nitric oxide synthase (nNOS)-dependent NO production in cultured VMH GI neurons.
912	17170237	The effects of glucose and leptin were mediated by suppression of AMP-activated protein kinase (AMPK).
913	17170237	The AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) increased both NO production and neuronal activity in GI neurons.
914	17170237	Furthermore, decreased glucose, insulin, and AICAR increase the phosphorylation of VMH nNOS, whereas leptin decreases it.
915	17170237	Thus NO may mediate, in part, glucose, leptin, and insulin signaling in VMH glucose-sensing neurons.
916	17496363	These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.
917	17513706	Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake.
918	17513706	The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined.
919	17513706	AMPK alpha(1) and alpha(2) activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise.
920	17513706	AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of beta-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged.
921	17513706	Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake.
922	17513706	The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined.
923	17513706	AMPK alpha(1) and alpha(2) activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise.
924	17513706	AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of beta-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged.
925	17513706	Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake.
926	17513706	The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined.
927	17513706	AMPK alpha(1) and alpha(2) activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise.
928	17513706	AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of beta-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged.
929	17513706	Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake.
930	17513706	The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined.
931	17513706	AMPK alpha(1) and alpha(2) activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise.
932	17513706	AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of beta-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged.
933	17709097	Dissociation of AMP-activated protein kinase and p38 mitogen-activated protein kinase signaling in skeletal muscle.
934	17709097	The p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling.
935	17709097	Here we used several different models of altered AMPK activity to determine whether p38 MAPK is a downstream intermediate of AMPK-mediated signaling in skeletal muscle.
936	17709097	First, L6 myoblasts and myotubes were treated with AICAR, an AMPK stimulator.
937	17709097	AMPK phosphorylation was significantly increased, but there was no change in p38 MAPK phosphorylation.
938	17709097	AMPKalpha2i TG mice did not exhibit any defect in basal or contraction-induced p38 MAPK phosphorylation.
939	17709097	Despite activated AMPK, basal p38 MAPK phosphorylation was not different between wild type and gamma1R70Q TG mice.
940	17709097	In addition, muscle contraction-induced p38 MAPK phosphorylation was significantly blunted in the gamma1R70Q TG mice.
941	17709097	In conclusion, increasing AMPK activity by AICAR and AMPKgamma1 mutation does not increase p38 MAPK phosphorylation in skeletal muscle.
942	17709097	Furthermore, AMPKalpha2i TG mice lacking contraction-stimulated AMPK activity have normal p38 MAPK phosphorylation.
943	17709097	These results suggest that p38 MAPK is not a downstream component of AMPK-mediated signaling in skeletal muscle.
944	18256313	The present study aims to determine whether adiponectin and AMPK are involved in the regulation of glycogen synthase (GS) in these structures.
945	18256313	Western blots of isolated distal tubules revealed the presence of adiponectin receptor ADIPOR1, catalytic AMPK subunits alpha(1) and alpha(2), their phosphorylated active forms, and the glycogen-binding AMPK subunit beta(2).
946	18256313	Expression levels of ADIPOR1, AMPKalpha(1), AMPKalpha(2), and AMPKbeta(2) were increased in streptozotocin-treated diabetic rats, whereas phosphorylated active AMPK levels were strongly decreased.
947	18256313	In vitro, 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR; 2 mM) and globular adiponectin (10 mug/ml) activated catalytic AMPK in distal tubules isolated from kidneys of normal rats but much more weakly in those from diabetic rats.
948	18256313	These results demonstrate that in distal tubular cells, adiponectin through luminal ADIPOR1 activates AMPK, leading to the inhibition of GS.
949	18276596	Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle.
950	18276596	The Akt substrate of 160 kDa (AS160) is phosphorylated on Akt substrate (PAS) motifs in response to insulin and contraction in skeletal muscle, regulating glucose uptake.
951	18276596	By immunoprecipitation and mass spectrometry, we identified this protein as the AS160 paralog TBC1D1, an obesity candidate gene regulating GLUT4 translocation in adipocytes.
952	18276596	In vivo stimulation by insulin, contraction, and the AMP-activated protein kinase (AMPK) activator AICAR increased TBC1D1 PAS phosphorylation.
953	18276596	Using mass spectrometry on TBC1D1 from mouse skeletal muscle, we identified several novel phosphorylation sites on TBC1D1 and found the majority were consensus or near consensus sites for AMPK.
954	18276596	Purified Akt and AMPK phosphorylated TBC1D1 in vitro, and AMPK, but not Akt, reduced TBC1D1 electrophoretic mobility.
955	18276596	TBC1D1 is a major PAS immunoreactive protein in skeletal muscle that is phosphorylated in vivo by insulin, AICAR, and contraction.
956	18276596	Both Akt and AMPK phosphorylate TBC1D1, but AMPK may be the more robust regulator.
957	18320901	Another AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-Driboruranoside (AICAR), also inhibited PDGF-induced proliferation.
958	18320901	Furthermore, cells treated with metformin or AICAR, also exhibited an attenuation in the rate of cytoskeletal remodeling, as quantified by spontaneous nanoscale motions of microbeads tightly anchored to the cytoskeleton (CSK) of the ASM cell.
959	18320901	Taken together, these findings suggest that metformin, probably through activation of AMPK, reduces the rate of ongoing reorganization of the CSK and inhibits ASM cell proliferation.
960	18320901	Another AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-Driboruranoside (AICAR), also inhibited PDGF-induced proliferation.
961	18320901	Furthermore, cells treated with metformin or AICAR, also exhibited an attenuation in the rate of cytoskeletal remodeling, as quantified by spontaneous nanoscale motions of microbeads tightly anchored to the cytoskeleton (CSK) of the ASM cell.
962	18320901	Taken together, these findings suggest that metformin, probably through activation of AMPK, reduces the rate of ongoing reorganization of the CSK and inhibits ASM cell proliferation.
963	18377870	Akt activation protects pancreatic beta cells from AMPK-mediated death through stimulation of mTOR.
964	18377870	In pancreatic beta cells this occurs under glucose limitation, or in the presence of the pharmacological AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR).
965	18377870	It is unknown whether Akt activation can counteract AMPK-mediated apoptosis, nor whether mTOR activation downstream of Akt mediates any survival signal in these conditions.
966	18377870	We report that expression of a constitutively active form of Akt increases mTOR activity and prevents apoptosis upon AMPK activation.
967	18377870	Expression of a constitutively active form of the mTOR target ribosomal protein S6 kinase (S6K) or of translation factor eIF4E reduced apoptosis by glucose limitation, and co-expression of S6K and eIF4E protected beta cells to the same extent as active Akt.
968	18377870	The protective effects of active Akt and S6K were associated with increased cellular protein synthesis activity.
969	18377870	It is concluded that Akt stimulation of mTOR and subsequent activation of the targets by which mTOR affects protein translation are required and sufficient mechanisms for Akt-mediated survival of beta cells undergoing sustained AMPK activation.
970	18562038	Effect of fasting on PPARgamma and AMPK activity in adipocytes.
971	18562038	PPARgamma mRNA levels decreased in the adipose tissues isolated from rats fasted for 39h, whereas adipocyte lipid-binding protein (aP2) and lipoprotein lipase (LPL) mRNA levels increased.
972	18562038	In addition, the effect of 5-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) on PPARgamma expression in primary cultured adipocytes was investigated.
973	18562038	AICAR reduced PPARgamma mRNA levels but increased aP2 and LPL mRNA levels.
974	18562038	Effect of fasting on PPARgamma and AMPK activity in adipocytes.
975	18562038	PPARgamma mRNA levels decreased in the adipose tissues isolated from rats fasted for 39h, whereas adipocyte lipid-binding protein (aP2) and lipoprotein lipase (LPL) mRNA levels increased.
976	18562038	In addition, the effect of 5-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) on PPARgamma expression in primary cultured adipocytes was investigated.
977	18562038	AICAR reduced PPARgamma mRNA levels but increased aP2 and LPL mRNA levels.
978	18641273	Both metformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside [AICAR, an AMP-activated protein kinase (AMPK) activator that is also activated by metformin] 1) diminished the tendency for the relaxation to reverse at high ACh concentrations and 2) suppressed both ACh-induced EDCF-mediated contraction and ACh-stimulated production of prostanoids (thromboxane A2 and PGE2).
979	18641273	Metformin did not alter the protein expressions of endothelial nitric oxide synthase (eNOS), phospho-eNOS (Ser1177), or COX-1, but it increased COX-2 protein.
980	19190259	We demonstrated previously that, in healthy young men, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR) stimulates human muscle 2-deoxyglucose (2DG) uptake without detectable activation of muscle AMP-activated protein kinase (AMPK) but with extracellular-regulated kinase 1/2 (ERK1/2) activation.
981	19190259	We determined 1) 2DG uptake, 2) total AMPKalpha activity, AMPK, acetyl-CoA carboxylase (ACC), and AS160 phosphorylation, and 3) ERK1/2 phosphorylation.
982	19190259	At 3-h AMPK activity and AMPK, ACC and AS160 phosphorylation were unchanged, but ERK1/2 phosphorylation increased at both AICAR doses.
983	19190259	We demonstrated previously that, in healthy young men, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR) stimulates human muscle 2-deoxyglucose (2DG) uptake without detectable activation of muscle AMP-activated protein kinase (AMPK) but with extracellular-regulated kinase 1/2 (ERK1/2) activation.
984	19190259	We determined 1) 2DG uptake, 2) total AMPKalpha activity, AMPK, acetyl-CoA carboxylase (ACC), and AS160 phosphorylation, and 3) ERK1/2 phosphorylation.
985	19190259	At 3-h AMPK activity and AMPK, ACC and AS160 phosphorylation were unchanged, but ERK1/2 phosphorylation increased at both AICAR doses.
986	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).
987	19223652	Finally, neither the AMPK inhibitor compound C nor the AMPK activator AICAR altered the activity of VMH GE neurons.
988	19223652	These data suggest that insulin attenuates the ability of VMH GE neurons to sense decreased glucose via the PI3K signaling pathway.
989	19357294	Hypothalamic AMP-activated protein kinase activation with AICAR amplifies counterregulatory responses to hypoglycemia in a rodent model of type 1 diabetes.
990	19357294	All groups subsequently underwent hyperinsulinemic hypoglycemic clamp studies on day 4 in conjunction with VMH microinjection with either saline (control) or AICAR (5-aminoimidazole-4-carboxamide) to activate AMPK.
991	19357294	Hypothalamic AMP-activated protein kinase activation with AICAR amplifies counterregulatory responses to hypoglycemia in a rodent model of type 1 diabetes.
992	19357294	All groups subsequently underwent hyperinsulinemic hypoglycemic clamp studies on day 4 in conjunction with VMH microinjection with either saline (control) or AICAR (5-aminoimidazole-4-carboxamide) to activate AMPK.
993	19635557	High glucose-induced oxidative stress alters estrogen effects on ERalpha and ERbeta in human endothelial cells: reversal by AMPK activator.
994	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.
995	19635557	The role of the AMPK activator AICAR was examined on modulating the effects of high glucose.
996	19635557	Protein levels of estrogen receptors, ERalpha and ERbeta, were measured through western blotting.
997	19635557	Under normal glucose, E2 increased the levels of ERalpha relative ERbeta; however, high glucose reversed the estrogen effects on endothelial ER expression.
998	19923418	Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle.
999	19923418	TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle.
1000	19923418	Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization.
1001	19923418	The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation.
1002	19923418	However, the 5'-AMP-activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites.
1003	19923418	Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4.
1004	19923418	Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro.
1005	19923418	Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli.
1006	19923418	S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle.
1007	19923418	Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle.
1008	19923418	TBC1D4 (also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle.
1009	19923418	Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization.
1010	19923418	The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation.
1011	19923418	However, the 5'-AMP-activated protein kinase (AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites.
1012	19923418	Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4.
1013	19923418	Recombinant AMPK, but not Akt1, Akt2, or PKCzeta, phosphorylated purified muscle TBC1D4 on S711 in vitro.
1014	19923418	Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli.
1015	19923418	S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle.
1016	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.
1017	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.
1018	20393162	Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment.
1019	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.
1020	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.
1021	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).
1022	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).
1023	20393162	Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes.
1024	20393162	Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment.
1025	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.
1026	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.
1027	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).
1028	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).
1029	20393162	Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes.
1030	20393162	Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment.
1031	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.
1032	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.
1033	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).
1034	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).
1035	20393162	Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes.
1036	20393162	Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment.
1037	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.
1038	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.
1039	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).
1040	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).
1041	20393162	Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes.
1042	20739620	A key enzyme in this process is pyruvate dehydrogenase kinase 4 (PDK4).
1043	20739620	We further postulated that the p38 mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase (AMPK) signaling pathways would control PDK4 mRNA expression in cultured adipose tissue.
1044	20739620	In cultured adipose tissue, epinephrine increased p38 and AMPK signaling; however, the direct activation of AMPK by AICAR or metformin led to reductions in PDK4 mRNA levels.
1045	20739620	The p38 inhibitor SB202190 reduced epinephrine-mediated increases in p38 MAPK activation without altering hormone-sensitive lipase or AMPK phosphorylation or attenuating epinephrine-induced increases in lipolysis.
1046	20739620	Reductions in p38 MAPK signaling were associated with decreases in PDK4 mRNA expression.
1047	20739620	Our results are the very first to demonstrate an epinephrine-mediated regulation of PDK4 mRNA levels in white adipose tissue and suggest that p38 MAPK and PPARγ could be involved in this pathway.
1048	20797423	Here we show that ER stress triggers a significant increase in expression of CCAAT/enhancer-binding protein (C/EBPβ) and phosphorylated CREB together with reduced phospho-AMP-activated protein kinase (pAMPK) in hepatoma cells.
1049	20797423	Chromatin immunoprecipitation assays demonstrate that C/EBPβ is recruited to the PEPCK promoter during ER stress and is reversed by pre-treatment with a JNK inhibitor that relieves ER stress.
1050	20797423	C/EBPβ but not pCREB was suppressed by the AMPK-activator AICAR or constitutively active AMPK, while dominant negative AMPK increased C/EBPβ expression.
1051	20797423	These data suggest that ER stress triggers suppression of AMPK while increasing C/EBPβ and pCREB expression which activates PEPCK gene transcription.
1052	21427411	AMP-activated protein kinase rescues the angiogenic functions of endothelial progenitor cells via manganese superoxide dismutase induction in type 1 diabetes.
1053	21427411	AMP-activated protein kinase (AMPK) activation has been shown to induce MnSOD and suppress hyperglycemia-induced mitochondrial ROS production in endothelial cells.
1054	21427411	We tested the hypothesis that AMPK activation rescues impaired EPC functions through MnSOD induction in type 1 diabetes.
1055	21427411	These beneficial effects of AICAR on MnSOD and EPC functions were significantly attenuated by silencing MnSOD or AMPK antagonist compound C pretreatment.
1056	21427411	Finally, the expression of protein phosphatase 2A, a key enzyme for AMPK dephosphorylation and inactivation, was increased in diabetic EPCs, and its inhibition by siRNA or okadaic acid reversed the deficient AMPK activation and MnSOD level in diabetic EPCs.
1057	21427411	These findings demonstrate for the first time that AMPK activation rescues impaired EPC functions and suppresses mitochondrial superoxide by inducing MnSOD in type 1 diabetes.
1058	21479175	Human insulin and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, decreased the hemolymph sugar levels of the hyperglycemic silkworms and restored growth.
1059	21479175	Treatment of the isolated fat body with human insulin in an in vitro culture system increased total sugar in the fat body and stimulated Akt phosphorylation.
1060	21479175	Moreover, AICAR stimulated AMPK phosphorylation in the silkworm fat body.
1061	21479175	Human insulin and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, decreased the hemolymph sugar levels of the hyperglycemic silkworms and restored growth.
1062	21479175	Treatment of the isolated fat body with human insulin in an in vitro culture system increased total sugar in the fat body and stimulated Akt phosphorylation.
1063	21479175	Moreover, AICAR stimulated AMPK phosphorylation in the silkworm fat body.
1064	21543418	The transcription factor upstream stimulatory factor 1 (USF1) is an important regulator of glucose-mediated transforming growth factor (TGF)-β1 expression in mesangial cells; however, its role in the development of diabetic kidney disease has not been evaluated.
1065	21543418	TGF-β1 and renin gene expression and protein were substantially increased in the WT diabetic mice but not in USF1 -/- diabetic mice.
1066	21543418	High glucose inhibited AMP-activated protein kinase (AMPK) activity and increased USF1 nuclear translocation.
1067	21543418	Activation of AMPK with AICAR stimulated AMPK activity and reduced nuclear accumulation of USF1.
1068	21543418	We thus conclude that USF1 is a critical transcription factor regulating diabetic kidney disease and plays a critical role in albuminuria, mesangial matrix accumulation, and TGF-β1 and renin stimulation in diabetic kidney disease.
1069	21543418	AMPK activity may play a key role in high glucose-induced regulation of USF1.
1070	21586697	The present study determined the dynamic change of adiponectin (APN, a cardioprotective adipokine), its receptor expression, and their impact upon myocardial ischemia/reperfusion (MI/R) injury during type 1 diabetes mellitus (T1DM) progression, and involved underlying mechanisms.
1071	21586697	Administration of globular APN (gAD) failed to attenuate MI/R injury in 1-wk T1DM mice, while an AMP-activated protein kinase (AMPK) activator (AICAR) reduced MI/R injury.
1072	21586697	In conclusion, our results demonstrate a dynamic dysfunction of APN/AdipoR1 during T1DM progression.
1073	21700896	Reductions in RIP140 are not required for exercise- and AICAR-mediated increases in skeletal muscle mitochondrial content.
1074	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.
1075	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.
1076	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.
1077	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.
1078	21700896	Reductions in RIP140 are not required for exercise- and AICAR-mediated increases in skeletal muscle mitochondrial content.
1079	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.
1080	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.
1081	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.
1082	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.
1083	21700896	Reductions in RIP140 are not required for exercise- and AICAR-mediated increases in skeletal muscle mitochondrial content.
1084	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.
1085	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.
1086	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.
1087	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.
1088	21937027	AMPK activation inhibits apoptosis and tau hyperphosphorylation mediated by palmitate in SH-SY5Y cells.
1089	21937027	We also observed increases in c-Jun N-terminal kinase (JNK) activation and tau hyperphosphorylation in response to palmitate.
1090	21937027	Although palmitate did not impair insulin signaling as shown by the immunoblotting analysis of AKT phosphorylation, it did inactivate AMP-activated protein kinase (AMPK).
1091	21937027	Activation of AMPK by N(1)-(β-d-Ribofuranosyl)-5-aminoimidazole-4-carboxamide (AICAR), significantly reduced the apoptosis of cells treated with palmitate.
1092	21937027	AICAR also significantly inhibited ER stress, resulting in reduced tau hyperphosphorylation in cells treated with palmitate.
1093	21937027	Similarly, A769662, a direct activator of AMPK, also abolished the ER stress-mediated apoptosis and tau hyperphosphorylation.
1094	21937027	Therefore, these data suggest that palmitate triggers ER stress-mediated lipotoxicity and that AMPK activation inhibits apoptosis and tau hyperphosphorylation mediated by palmitate in SH-SY5Y cells.
1095	21937027	AMPK activation inhibits apoptosis and tau hyperphosphorylation mediated by palmitate in SH-SY5Y cells.
1096	21937027	We also observed increases in c-Jun N-terminal kinase (JNK) activation and tau hyperphosphorylation in response to palmitate.
1097	21937027	Although palmitate did not impair insulin signaling as shown by the immunoblotting analysis of AKT phosphorylation, it did inactivate AMP-activated protein kinase (AMPK).
1098	21937027	Activation of AMPK by N(1)-(β-d-Ribofuranosyl)-5-aminoimidazole-4-carboxamide (AICAR), significantly reduced the apoptosis of cells treated with palmitate.
1099	21937027	AICAR also significantly inhibited ER stress, resulting in reduced tau hyperphosphorylation in cells treated with palmitate.
1100	21937027	Similarly, A769662, a direct activator of AMPK, also abolished the ER stress-mediated apoptosis and tau hyperphosphorylation.
1101	21937027	Therefore, these data suggest that palmitate triggers ER stress-mediated lipotoxicity and that AMPK activation inhibits apoptosis and tau hyperphosphorylation mediated by palmitate in SH-SY5Y cells.
1102	21945951	The activation of the p53 pathway by the AMP mimetic AICAR is reduced by inhibitors of the ATM or mTOR kinases.
1103	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.
1104	21945951	The activation of the p53 tumor suppressor protein by metabolic stress has been shown to be mediated by AMPK.
1105	21945951	We showed that AICAR activated the p53 pathway in LKB1-deficient cells.
1106	21945951	In cells with ATM expression silenced by shRNA, AICAR-induced p53 phosphorylation at Ser(15) and Ser(37) was attenuated.
1107	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.
1108	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).
1109	21945951	Thus, ATM and mTOR participate in the activation of p53 in response to a compound mimicking metabolic stress.
1110	21945951	The activation of the p53 pathway by the AMP mimetic AICAR is reduced by inhibitors of the ATM or mTOR kinases.
1111	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.
1112	21945951	The activation of the p53 tumor suppressor protein by metabolic stress has been shown to be mediated by AMPK.
1113	21945951	We showed that AICAR activated the p53 pathway in LKB1-deficient cells.
1114	21945951	In cells with ATM expression silenced by shRNA, AICAR-induced p53 phosphorylation at Ser(15) and Ser(37) was attenuated.
1115	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.
1116	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).
1117	21945951	Thus, ATM and mTOR participate in the activation of p53 in response to a compound mimicking metabolic stress.
1118	21945951	The activation of the p53 pathway by the AMP mimetic AICAR is reduced by inhibitors of the ATM or mTOR kinases.
1119	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.
1120	21945951	The activation of the p53 tumor suppressor protein by metabolic stress has been shown to be mediated by AMPK.
1121	21945951	We showed that AICAR activated the p53 pathway in LKB1-deficient cells.
1122	21945951	In cells with ATM expression silenced by shRNA, AICAR-induced p53 phosphorylation at Ser(15) and Ser(37) was attenuated.
1123	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.
1124	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).
1125	21945951	Thus, ATM and mTOR participate in the activation of p53 in response to a compound mimicking metabolic stress.
1126	21945951	The activation of the p53 pathway by the AMP mimetic AICAR is reduced by inhibitors of the ATM or mTOR kinases.
1127	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.
1128	21945951	The activation of the p53 tumor suppressor protein by metabolic stress has been shown to be mediated by AMPK.
1129	21945951	We showed that AICAR activated the p53 pathway in LKB1-deficient cells.
1130	21945951	In cells with ATM expression silenced by shRNA, AICAR-induced p53 phosphorylation at Ser(15) and Ser(37) was attenuated.
1131	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.
1132	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).
1133	21945951	Thus, ATM and mTOR participate in the activation of p53 in response to a compound mimicking metabolic stress.
1134	21945951	The activation of the p53 pathway by the AMP mimetic AICAR is reduced by inhibitors of the ATM or mTOR kinases.
1135	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.
1136	21945951	The activation of the p53 tumor suppressor protein by metabolic stress has been shown to be mediated by AMPK.
1137	21945951	We showed that AICAR activated the p53 pathway in LKB1-deficient cells.
1138	21945951	In cells with ATM expression silenced by shRNA, AICAR-induced p53 phosphorylation at Ser(15) and Ser(37) was attenuated.
1139	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.
1140	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).
1141	21945951	Thus, ATM and mTOR participate in the activation of p53 in response to a compound mimicking metabolic stress.
1142	22778921	Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter.
1143	22778921	These data indicate a different route to increase skeletal muscle GLUT4 expression, through the potential inhibition of the enzyme AICAR transformylase.
1144	22778921	Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter.
1145	22778921	These data indicate a different route to increase skeletal muscle GLUT4 expression, through the potential inhibition of the enzyme AICAR transformylase.
1146	23116613	The human glucagon-like peptide-1 analogue liraglutide regulates pancreatic beta-cell proliferation and apoptosis via an AMPK/mTOR/P70S6K signaling pathway.
1147	23116613	The purpose of the present study was to explore whether liraglutide, a human GLP-1 analogue, protects beta cells via AMPK/mTOR signaling.
1148	23116613	Liraglutide (100 nmol/L) activated mTOR and its downstream effectors, 70-kDa ribosomal protein S6 kinase and eIF4E-binding protein-1, in INS-1 cells.
1149	23116613	This effect was abated by pathway blockers: the AMPK activator AICAR and the mTOR inhibitor rapamycin.
1150	23116613	These results suggest that the enhancement of beta-cell proliferation by that GLP-1 receptor agonist liraglutide is mediated, at least in part, by AMPK/mTOR signaling.
1151	23341495	Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose.
1152	23341495	Glucagon-like peptide-1 (GLP-1) suppresses food intake via activation of a central (i.e., brain) GLP-1 receptor (GLP-1R).
1153	23341495	The anorectic effect elicited by hindbrain GLP-1R activation is attenuated by the AMPK stimulator AICAR.
1154	23341495	This suggests that central GLP-1R activation suppresses food intake via inhibition of central AMPK.
1155	23341495	The present studies examined the mechanism(s) by which central GLP-1R activation inhibits AMPK.
1156	23341495	In summary, we propose a model whereby activation of the central GLP-1R reduces food intake via glucose metabolism-dependent inhibition of central AMPK.
1157	23698110	Inhibition of the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 by AICAR.
1158	23698110	AMP-activated protein kinase (AMPK) contributes to the acceleration of insulin signaling.
1159	23698110	However, the mechanism by which AMPK regulates insulin signaling remains unclear.
1160	23698110	Here we investigated the role of AMPK in serine phosphorylation of IRS-1 at 636/639 and 307, which is induced by tumor necrosis factor (TNF)-α in 3T3L1 adipocytes.
1161	23698110	We demonstrated that the AMPK activator 5-aminoimidazole-4-carboxamide-1-d-ribofuranoside (AICAR) significantly inhibited the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by suppression of extracellular signal-regulated kinase (ERK) phosphorylation but not c-Jun-NH2-terminal kinase (JNK) phosphorylation.
1162	23698110	In addition, AICAR stimulation resulted in enhanced interaction between ERK and MAP kinase phosphatase-4 (DUSP9/MKP-4) without affecting DUSP9/MPK4 mRNA synthesis.
1163	23698110	Moreover, intraperitoneal administration (0.25 g/kg) of AICAR to db/db mice improved blood glucose levels and inhibited the phosphorylation of ERK in adipose tissue.
1164	23698110	In conclusion, we propose a new mechanism in which AICAR suppresses TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by enhancing the interaction between ERK and DUSP9/MKP-4.
1165	23698110	Inhibition of the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 by AICAR.
1166	23698110	AMP-activated protein kinase (AMPK) contributes to the acceleration of insulin signaling.
1167	23698110	However, the mechanism by which AMPK regulates insulin signaling remains unclear.
1168	23698110	Here we investigated the role of AMPK in serine phosphorylation of IRS-1 at 636/639 and 307, which is induced by tumor necrosis factor (TNF)-α in 3T3L1 adipocytes.
1169	23698110	We demonstrated that the AMPK activator 5-aminoimidazole-4-carboxamide-1-d-ribofuranoside (AICAR) significantly inhibited the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by suppression of extracellular signal-regulated kinase (ERK) phosphorylation but not c-Jun-NH2-terminal kinase (JNK) phosphorylation.
1170	23698110	In addition, AICAR stimulation resulted in enhanced interaction between ERK and MAP kinase phosphatase-4 (DUSP9/MKP-4) without affecting DUSP9/MPK4 mRNA synthesis.
1171	23698110	Moreover, intraperitoneal administration (0.25 g/kg) of AICAR to db/db mice improved blood glucose levels and inhibited the phosphorylation of ERK in adipose tissue.
1172	23698110	In conclusion, we propose a new mechanism in which AICAR suppresses TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by enhancing the interaction between ERK and DUSP9/MKP-4.
1173	23698110	Inhibition of the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 by AICAR.
1174	23698110	AMP-activated protein kinase (AMPK) contributes to the acceleration of insulin signaling.
1175	23698110	However, the mechanism by which AMPK regulates insulin signaling remains unclear.
1176	23698110	Here we investigated the role of AMPK in serine phosphorylation of IRS-1 at 636/639 and 307, which is induced by tumor necrosis factor (TNF)-α in 3T3L1 adipocytes.
1177	23698110	We demonstrated that the AMPK activator 5-aminoimidazole-4-carboxamide-1-d-ribofuranoside (AICAR) significantly inhibited the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by suppression of extracellular signal-regulated kinase (ERK) phosphorylation but not c-Jun-NH2-terminal kinase (JNK) phosphorylation.
1178	23698110	In addition, AICAR stimulation resulted in enhanced interaction between ERK and MAP kinase phosphatase-4 (DUSP9/MKP-4) without affecting DUSP9/MPK4 mRNA synthesis.
1179	23698110	Moreover, intraperitoneal administration (0.25 g/kg) of AICAR to db/db mice improved blood glucose levels and inhibited the phosphorylation of ERK in adipose tissue.
1180	23698110	In conclusion, we propose a new mechanism in which AICAR suppresses TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by enhancing the interaction between ERK and DUSP9/MKP-4.
1181	23698110	Inhibition of the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 by AICAR.
1182	23698110	AMP-activated protein kinase (AMPK) contributes to the acceleration of insulin signaling.
1183	23698110	However, the mechanism by which AMPK regulates insulin signaling remains unclear.
1184	23698110	Here we investigated the role of AMPK in serine phosphorylation of IRS-1 at 636/639 and 307, which is induced by tumor necrosis factor (TNF)-α in 3T3L1 adipocytes.
1185	23698110	We demonstrated that the AMPK activator 5-aminoimidazole-4-carboxamide-1-d-ribofuranoside (AICAR) significantly inhibited the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by suppression of extracellular signal-regulated kinase (ERK) phosphorylation but not c-Jun-NH2-terminal kinase (JNK) phosphorylation.
1186	23698110	In addition, AICAR stimulation resulted in enhanced interaction between ERK and MAP kinase phosphatase-4 (DUSP9/MKP-4) without affecting DUSP9/MPK4 mRNA synthesis.
1187	23698110	Moreover, intraperitoneal administration (0.25 g/kg) of AICAR to db/db mice improved blood glucose levels and inhibited the phosphorylation of ERK in adipose tissue.
1188	23698110	In conclusion, we propose a new mechanism in which AICAR suppresses TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by enhancing the interaction between ERK and DUSP9/MKP-4.
1189	23698110	Inhibition of the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 by AICAR.
1190	23698110	AMP-activated protein kinase (AMPK) contributes to the acceleration of insulin signaling.
1191	23698110	However, the mechanism by which AMPK regulates insulin signaling remains unclear.
1192	23698110	Here we investigated the role of AMPK in serine phosphorylation of IRS-1 at 636/639 and 307, which is induced by tumor necrosis factor (TNF)-α in 3T3L1 adipocytes.
1193	23698110	We demonstrated that the AMPK activator 5-aminoimidazole-4-carboxamide-1-d-ribofuranoside (AICAR) significantly inhibited the TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by suppression of extracellular signal-regulated kinase (ERK) phosphorylation but not c-Jun-NH2-terminal kinase (JNK) phosphorylation.
1194	23698110	In addition, AICAR stimulation resulted in enhanced interaction between ERK and MAP kinase phosphatase-4 (DUSP9/MKP-4) without affecting DUSP9/MPK4 mRNA synthesis.
1195	23698110	Moreover, intraperitoneal administration (0.25 g/kg) of AICAR to db/db mice improved blood glucose levels and inhibited the phosphorylation of ERK in adipose tissue.
1196	23698110	In conclusion, we propose a new mechanism in which AICAR suppresses TNF-α-induced serine phosphorylation of IRS-1 at 636/639 and 307 by enhancing the interaction between ERK and DUSP9/MKP-4.
1197	23761105	Contraction and AICAR stimulate IL-6 vesicle depletion from skeletal muscle fibers in vivo.
1198	23761105	However, contraction-mediated IL-6-EGFP reduction was normal in muscle-specific AMP-activated protein kinase (AMPK) α2-inactive transgenic mice.
1199	23761105	In contrast, the AMPK activator AICAR decreased IL-6-EGFP vesicles, an effect that was inhibited in the transgenic mice.
1200	23761105	Contraction and AICAR stimulate IL-6 vesicle depletion from skeletal muscle fibers in vivo.
1201	23761105	However, contraction-mediated IL-6-EGFP reduction was normal in muscle-specific AMP-activated protein kinase (AMPK) α2-inactive transgenic mice.
1202	23761105	In contrast, the AMPK activator AICAR decreased IL-6-EGFP vesicles, an effect that was inhibited in the transgenic mice.
1203	23967267	Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside administration despite reducing hypothalamic AMP-activated protein kinase phosphorylation in insulin-deficient rats.
1204	23967267	This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats.
1205	23967267	Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3).
1206	23967267	In non-diabetic rats, despite reducing adiposity, AICAR increased (∼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively.
1207	23967267	The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals.
1208	23967267	Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR.
1209	23967267	Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside administration despite reducing hypothalamic AMP-activated protein kinase phosphorylation in insulin-deficient rats.
1210	23967267	This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats.
1211	23967267	Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3).
1212	23967267	In non-diabetic rats, despite reducing adiposity, AICAR increased (∼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively.
1213	23967267	The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals.
1214	23967267	Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR.
1215	23967267	Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside administration despite reducing hypothalamic AMP-activated protein kinase phosphorylation in insulin-deficient rats.
1216	23967267	This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats.
1217	23967267	Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3).
1218	23967267	In non-diabetic rats, despite reducing adiposity, AICAR increased (∼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively.
1219	23967267	The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals.
1220	23967267	Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR.
1221	23967267	Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside administration despite reducing hypothalamic AMP-activated protein kinase phosphorylation in insulin-deficient rats.
1222	23967267	This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats.
1223	23967267	Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3).
1224	23967267	In non-diabetic rats, despite reducing adiposity, AICAR increased (∼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively.
1225	23967267	The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals.
1226	23967267	Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR.
1227	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.
1228	24008375	The human HCC cell lines HepG2 and PLC/PRF/5 were cultured and treated with metformin or 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an activator of adenosine monophosphate (AMP)-activated protein kinase.