ATP-Sensitive potassium channels modulate glucose transport in cultured human skeletal muscle cells

Endocr J. 2001 Jun;48(3):369-75. doi: 10.1507/endocrj.48.369.

Abstract

Several lines of evidence suggest that ATP-sensitive potassium (KATP) channels are involved in glucose uptake by insulin target tissues. The aim of the present study was to prove directly the effect of KATP channel activity on glucose transport into cultured human skeletal muscle cells. We used potassium channel openers PCO-400 and nicorandil alone or in combination with channel blockers glibenclamide and gliclazide to examine their effects on insulin- or high glucose concentration-induced glucose uptake using 2-deoxy-D-3H-glucose or 3-O-methyl-D-3H-glucose as tracer, respectively. PCO-400 inhibited the basal (non-stimulated) uptake of 2-DG or 3-OMG at the glucose concentration of 5 mM. PCO-400 and nicorandil dose-dependently inhibited insulin-stimulated glucose uptake, and their inhibitory effects were reversed by glibenclamide or gliclazide. In addition, PCO-400 inhibited high glucose concentration-facilitated glucose transport in the absence of insulin, and this effect was also antagonized by both sulfonylurea drugs. Regarding the mechanism by which KATP channels modulate glucose transport, we focused on protein kinase C (PKC), because PKC has been supposed to participate in both insulin- and high glucose concentration-stimulated glucose transport. PMA (phorbol 12-myristate 13-acetate) dose-dependently reversed the PCO-400-induced suppression of insulin-stimulated glucose uptake. On the other hand, PCO-400 at the concentration that inhibited glucose uptake caused no alteration of membrane-associated PKC activity in the presence of insulin or PMA. From these results we conclude that KATP channels modulate the basal and insulin-or high glucose level-stimulated glucose transport in skeletal muscle through a mechanism independent of PKC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-O-Methylglucose / metabolism
  • 3-O-Methylglucose / pharmacology
  • Adenosine Triphosphate / pharmacology*
  • Benzopyrans / pharmacology
  • Biological Transport / drug effects
  • Cells, Cultured
  • Cyclopentanes / pharmacology
  • Deoxyglucose / metabolism
  • Enzyme Activation / drug effects
  • Gliclazide / pharmacology
  • Glucose / metabolism*
  • Glyburide / pharmacology
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Ion Channel Gating / drug effects
  • Muscle, Skeletal / metabolism*
  • Nicorandil / pharmacology
  • Potassium Channel Blockers
  • Potassium Channels / physiology*
  • Protein Kinase C / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Benzopyrans
  • Cyclopentanes
  • Hypoglycemic Agents
  • Insulin
  • Potassium Channel Blockers
  • Potassium Channels
  • SDZ PCO 400
  • 3-O-Methylglucose
  • Nicorandil
  • Adenosine Triphosphate
  • Deoxyglucose
  • Protein Kinase C
  • Gliclazide
  • Glucose
  • Tetradecanoylphorbol Acetate
  • Glyburide