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

Am J Physiol Cell Physiol. 2007 Jan;292(1):C564-72. doi: 10.1152/ajpcell.00269.2006. Epub 2006 Jul 26.

Abstract

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 AMPKalpha(1)) and dominant-negative (DN; which depletes endogenous AMPKalpha) forms of AMPKalpha (Ad-AMPKalpha-CA and Ad-AMPKalpha-DN, respectively) into C(2)C(12) myotubes. Compared with control (Ad-green 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-1beta-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 AMPKalpha(1) is sufficient to increase insulin action and that the presence of functional AMPKalpha is required for 5-aminoimidazole-4-carboxamide-1beta,D-ribofuranoside-related increases in insulin action.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Biological Transport / drug effects
  • Cells, Cultured
  • Drug Synergism
  • Enzyme Activators / pharmacology
  • Genes, Dominant
  • Glucose / metabolism*
  • Green Fluorescent Proteins
  • Hypoglycemic Agents / metabolism*
  • Insulin / metabolism*
  • Insulin Receptor Substrate Proteins
  • Isoenzymes / pharmacology
  • Luminescent Agents
  • Mice
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / pharmacology*
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / pharmacology*
  • Ribonucleotides / pharmacology
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases

Substances

  • Enzyme Activators
  • Hypoglycemic Agents
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Isoenzymes
  • Luminescent Agents
  • Multienzyme Complexes
  • Phosphoproteins
  • Ribonucleotides
  • Green Fluorescent Proteins
  • Aminoimidazole Carboxamide
  • Protein Kinases
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide
  • Glucose