Interleukin-1β-induced stimulation of insulin release in mouse pancreatic islets is related to diacylglycerol production and protein kinase C activation

Décio L. Eizirik, Stellan Sandler, Nils Welsh, Lisa Juntti-Berggren, Per Olof Berggren

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The aim of the present study was to investigate the mechanisms responsible for the acute, stimulatory effects of interleukin-1β (rIL-1β; 1 ng/ml) on insulin release from mouse pancreatic islets. For this purpose, mouse islets were exposed for 60-120 min to rIL-1β and their function and metabolism characterized during this period. The cytokine did not increase insulin release in the presence of 1.7 mM glucose, but both in the presence of 5.6 or 16.7 mM glucose, or 10 mM leucine + 2 mM glutamine, it induced a 60-100% increase in insulin release. Moreover, rIL-1β also enhanced the effects of 1 μ/ml glipizide on insulin release, but failed to increase insulin release induced by 30 mM KCl or by glucose plus phorbol ester (TPA; 100 nM). These early stimulatory effects of rIL-1β on insulin release were neither accompanied by major increases in glucose or amino acid metabolism, nor by modifications in islet cAMP content, and they were prevented by mannoheptulose, diazoxide or verapamil. rIL-1β potentiation of glucose-induced insulin release was not accompanied by modifications in [Ca2+]i, but the cytokine increased diacylglycerol production and induced protein kinase C (PKC) activation. Down-regulation of PKC completely prevented the stimulatory effects of rIL-1β on glucose-induced insulin release. In conclusion, rIL-1β induces an early stimulation of insulin release in mouse β-cells by a mechanism independent of glucose metabolism, cAMP generation or modifications in [Ca2+]i. This effect is probably related to diacylglycerol formation and stimulation of PKC.

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume111
Issue number2
DOIs
StatePublished - Jun 1995

    Fingerprint

Keywords

  • Diacylglycerol
  • Insulin release
  • Interleukin-1β
  • Pancreatic β-cells
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this