PMID- 11117997
OWN - NLM
STAT- MEDLINE
DCOM- 20010104
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 49
IP  - 12
DP  - 2000 Dec
TI  - Activation of glucose transport by AMP-activated protein kinase via stimulation 
      of nitric oxide synthase.
PG  - 1978-85
AB  - Glucose transport in skeletal muscle is stimulated by two distinct stimuli, 
      insulin and exercise. The mechanism by which exercise stimulates glucose 
      transport is not known, although it is distinct from the insulin-mediated 
      pathway. Recently, it has been shown that AMP-activated protein kinase (AMPK) is 
      activated by exercise in skeletal muscle, whereas pharmacological activation of 
      AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) leads to increased 
      glucose transport. It has been postulated, therefore, that AMPK may be the link 
      between exercise and glucose transport. To address this, we have examined the 
      signaling pathway involved in the stimulation of glucose uptake after activation 
      of AMPK. Here we show that activation of AMPK by AICAR in rat muscle and mouse 
      H-2Kb muscle cells activates glucose transport approximately twofold. AMPK in 
      H-2Kb cells is also activated by hyperosmotic stress and the mitochondrial 
      uncoupling agent, dinitrophenol, both of which lead to increased glucose 
      transport. In contrast, insulin, which activates glucose transport two- 
      to-threefold in both rat muscle and H-2Kb cells, has no effect on AMPK activity. 
      A previous study has shown that AMPK phosphorylates and activates endothelial 
      nitric oxide synthase (NOS). We show here that NOS activity in H-2Kb cells is 
      activated after stimulation of AMPK by AICAR. Treatment of H-2Kb cells or rat 
      muscle with NOS inhibitors completely blocks the increase in glucose transport 
      after activation of AMPK. In addition, an inhibitor of guanylate cyclase also 
      blocks activation of glucose transport by AICAR in H-2Kb cells. These results 
      indicate that activation of AMPK in muscle cells stimulates glucose transport by 
      activation of NOS coupled to downstream signaling components, including cyclic 
      GMP.
FAU - Fryer, L G
AU  - Fryer LG
AD  - Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College School of 
      Medicine, Hammersmith Hospital, London, UK.
FAU - Hajduch, E
AU  - Hajduch E
FAU - Rencurel, F
AU  - Rencurel F
FAU - Salt, I P
AU  - Salt IP
FAU - Hundal, H S
AU  - Hundal HS
FAU - Hardie, D G
AU  - Hardie DG
FAU - Carling, D
AU  - Carling D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Dinitrophenols)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insulin)
RN  - 0 (Ribonucleotides)
RN  - 0 (Uncoupling Agents)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - 415SHH325A (Adenosine Monophosphate)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 2.7.- (Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adenosine Monophosphate/*physiology
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Biological Transport/drug effects/physiology
MH  - Cells, Cultured
MH  - Dinitrophenols/pharmacology
MH  - Enzyme Activation/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Glucose/*metabolism
MH  - Hindlimb
MH  - Humans
MH  - In Vitro Techniques
MH  - Insulin/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Muscle, Skeletal/cytology/metabolism
MH  - Nitric Oxide Synthase/antagonists & inhibitors/*metabolism/*physiology
MH  - Osmotic Pressure
MH  - Protein Kinases/*metabolism/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribonucleotides/pharmacology
MH  - Uncoupling Agents/pharmacology
EDAT- 2000/12/16 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/12/16 11:00
PHST- 2000/12/16 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/12/16 11:00 [entrez]
AID - 10.2337/diabetes.49.12.1978 [doi]
PST - ppublish
SO  - Diabetes. 2000 Dec;49(12):1978-85. doi: 10.2337/diabetes.49.12.1978.