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%).
| Original language | English |
|---|---|
| Journal | Diabetologia |
| Volume | 38 |
| Issue number | 9 |
| Pages (from-to) | 1025-32 |
| Number of pages | 8 |
| ISSN | 0012-186X |
| Publication status | Published - Sept 1995 |
Keywords
- Adenosine Triphosphate
- Animals
- Animals, Newborn
- Calcium
- Carbamates
- Cell Line
- Cells, Cultured
- Cytosol
- Dose-Response Relationship, Drug
- Glyburide
- Hypoglycemic Agents
- Ion Channel Gating
- Islets of Langerhans
- Kinetics
- Membrane Potentials
- Mice
- Patch-Clamp Techniques
- Piperidines
- Potassium Channels
- Rats
- Serum Albumin
- Time Factors
- Verapamil