Activation of AMPK is essential for AICAR-induced glucose uptake by skeletal muscle but not adipocytes.
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) reportedly activates AMP-activated protein kinase (AMPK) and stimulates glucose uptake by skeletal muscle cells. In this study, we investigated the role of AMPK in AICAR-induced glucose uptake by 3T3-L1 adipocytes and rat soleus muscle cells by overexpressing wild-type and dominant negative forms of the AMPKalpha2 subunit by use of adenovirus-mediated gene transfer. Overexpression of the dominant negative mutant had no effect on AICAR-induced glucose transport in adipocytes, although AMPK activation was almost completely abolished. This suggests that AICAR-induced glucose uptake by 3T3-L1 adipocytes is independent of AMPK activation. By contrast, overexpression of the dominant negative AMPKalpha2 mutant in muscle markedly suppressed both AICAR-induced glucose uptake and AMPK activation, although insulin-induced uptake was unaffected. Overexpression of the wild-type AMPKalpha2 subunit significantly increased AMPK activity in muscle but did not enhance glucose uptake. Thus, although AMPK activation may not, by itself, be sufficient to increase glucose transport, it appears essential for AICAR-induced glucose uptake in muscle.
Sakoda
Hideyuki
H
Institute for Adult Disease, Asahi Life Foundation, Tokyo 116, Japan.
Ogihara
Takehide
T
Anai
Motonobu
M
Fujishiro
Midori
M
Ono
Hiraku
H
Onishi
Yukiko
Y
Katagiri
Hideki
H
Abe
Miho
M
Fukushima
Yasushi
Y
Shojima
Nobuhiro
N
Inukai
Kouichi
K
Kikuchi
Masatoshi
M
Oka
Yoshitomo
Y
Asano
Tomoichiro
T
D016475:3T3 Cells; D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D004789:Enzyme Activation; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007163:Immunosorbent Techniques; D007328:Insulin / Q000494:pharmacology; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins; D012265:Ribonucleotides / Q000494:pharmacology*; D014162:Transfection
D007004:Hypoglycemic Agents; D007328:Insulin; D008164:Luminescent Proteins; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; D012265:Ribonucleotides; D049452:Green Fluorescent Proteins; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose