Effects of the Hypoglycaemic Drugs Repaglinide and Glibenclamide on ATP-sensitive Potassium-Channels and Cytosolic Calcium Levels in Beta TC3 Cells and Rat Pancreatic Beta Cells

Diabetologia. 1995 Sep;38(9):1025-32. doi: 10.1007/BF00402171.

Abstract

The present study demonstrates the action of the hypoglycaemic drugs repaglinide and glibenclamide in cultured newborn rat islet cells and mouse beta TC3 cells. In cell-attached membrane patches of newborn rat islet cells repaglinide (10 nmol/l) and glibenclamide (20 nmol/l) decrease the open probability of single ATP-sensitive K(+)-channels to approximately 10% of the activity prior to addition of the drugs in short-term experiments (< 5 min). The influence of repaglinide and glibenclamide on the ATP-sensitive K+ current was studied using the whole-cell patch clamp configuration. A half-maximal steady-state inhibition of the ATP-sensitive K+ currents is observed at 89 pmol/l repaglinide and at 47 pmol/l glibenclamide in whole-cell experiments of longer duration (30 min). Applying digital Ca2+ imaging on single beta TC3 cells we found that repaglinide and glibenclamide induced a concentration-dependent increase in intracellular free Ca2+ concentration ([Ca2+]i) with a half-maximal effect at 0.5 nmol/l for both drugs in long-term experiments (30 min). The rise in [Ca2+]i results from Ca2+ entry through voltage-dependent L-type Ca(2+)-channels since it is inhibited by verapamil (10 mumol/l). The effect of repaglinide and glibenclamide is partly reversible (approximately 80%).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Animals, Newborn
  • Calcium / metabolism
  • Carbamates / pharmacology*
  • Cell Line
  • Cells, Cultured
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Glyburide / pharmacology*
  • Hypoglycemic Agents / pharmacology*
  • Ion Channel Gating / drug effects
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology
  • Kinetics
  • Membrane Potentials / drug effects
  • Mice
  • Patch-Clamp Techniques
  • Piperidines / pharmacology*
  • Potassium Channels / drug effects
  • Potassium Channels / physiology*
  • Rats
  • Serum Albumin / pharmacology
  • Time Factors
  • Verapamil / pharmacology

Substances

  • Carbamates
  • Hypoglycemic Agents
  • Piperidines
  • Potassium Channels
  • Serum Albumin
  • repaglinide
  • Adenosine Triphosphate
  • Verapamil
  • Glyburide
  • Calcium