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Tolbutamide and diazoxide modulate phospholipase C-linked Ca(2+) signaling and insulin secretion in beta-cells

C Schöfl1, J Börger, T Mader

  • 1Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, 30623 Hannover, Germany. schefl.christof@mh-hannover.de

American Journal of Physiology. Endocrinology and Metabolism
|April 6, 2000
PubMed

Insights

Tolbutamide and diazoxide regulate pancreatic beta-cell function by affecting calcium signaling and insulin release through ATP-sensitive potassium channels. These drugs modulate voltage-sensitive calcium influx, impacting glucose-induced insulin secretion.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Pharmacology

Background:

  • Arginine vasopressin (AVP), bombesin, and acetylcholine (ACh) stimulate insulin release by activating phospholipase C (PLC)-linked receptors, increasing intracellular calcium.
  • ATP-sensitive potassium (K(ATP)) channels play a crucial role in regulating beta-cell function and insulin secretion.

Purpose of the Study:

  • To investigate the interaction between tolbutamide (K(ATP) channel closer) and diazoxide (K(ATP) channel opener) with PLC-linked calcium signaling and insulin secretion in pancreatic beta-cells.
  • To determine the role of K(ATP) channels in modulating calcium influx and insulin release in response to PLC-linked agonists.

Main Methods:

  • Experiments were conducted using HIT-T15 cells and mouse beta-cells.
  • Measurements included cytosolic free Ca(2+) levels and insulin secretion.
  • The effects of tolbutamide and diazoxide were assessed in the presence and absence of glucose, and in response to AVP and bombesin stimulation.

Main Results:

  • Tolbutamide enhanced and diazoxide inhibited PLC-linked Ca(2+) signals in glucose conditions, effects mimicked by L-type Ca(2+) channel modulators.
  • Neither drug affected internal Ca(2+) mobilization or store-operated Ca(2+) influx.
  • Tolbutamide potentiated and diazoxide inhibited AVP/bombesin-induced insulin secretion, with these effects being dependent on voltage-sensitive Ca(2+) influx.

Conclusions:

  • Tolbutamide and diazoxide modulate both PLC-linked Ca(2+) signaling and insulin secretion in pancreatic beta-cells.
  • These modulations are achieved by altering K(ATP) channel activity, thereby influencing voltage-sensitive Ca(2+) influx.
  • The study highlights the intricate interplay between K(ATP) channels and PLC-mediated pathways in regulating beta-cell function.

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