Potentiation of insulin-stimulated glucose transport by the AMP-activated protein kinase

Data from the use of activators and inhibitors of the AMP-activated protein kinase (AMPK) suggest that AMPK increases sensitivity of glucose transport to stimulation by insulin in muscle cells. We assayed insulin action after adenoviral (Ad) transduction of constitutively active (CA; a truncated form of AMPK[[alpha].sub.1]) and dominant-negative (DN; which depletes endogenous AMPK[alpha]) forms of AMPK[alpha] (Ad-AMPK[alpha]-CA and Ad-AMPK[alpha]-DN, respectively) into [C.sub.2][C.sub.12] myotubes. Compared with control (Adgreen fluorescent protein), Ad-AMPK-CA increased the ability of insulin to stimulate glucose transport. The increased insulin action in cells expressing AMPK-CA was suppressed by compound C (an AMPK inhibitor). Exposure of cells to 5-aminoimidazole-4-carboxamide-l[beta]-D-ribofuranoside (an AMPK activator) increased insulin action in uninfected myotubes and myotubes transduced with green fluorescent protein but not in Ad-AMPK-DN-infected myotubes. In Ad-AMPK-CA-transduced cells, serine phosphorylation of insulin receptor substrate 1 was decreased at a mammalian target of rapamycin (or p70 S6 kinase) target site that has been reported to be associated with insulin resistance. These data suggest that, in myotubes, activated AMPK[[alpha].sub.1] is sufficient to increase insulin action and that the presence of functional AMPK[alpha] is required for 5-aminoimidazole-4-carboxamide-1[beta],D-ribofuranoside-related increases in insulin action. compound C; AMPK; insulin sensitivity; Akt; mTOR