Mastoparan stimulates insulin secretion from pancreatic β-cells by effects at a late stage in the secretory pathway

doi:10.1016/0303-7207(93)90056-P

Molecular and Cellular Endocrinology

Volume 94, Issue 1, July 1993, Pages 97-103

https://doi.org/10.1016/0303-7207(93)90056-P Get rights and content

Abstract

Mastoparan (MP) is a component of wasp venom which stimulates secretion from a number of cell types. We have used intact and electrically permeabilised islets of Langerhans to investigate the mechanisms through which MP stimulates insulin secretion from pancreatic β-cells. MP caused a temperature-dependent and dose-related stimulation of insulin secretion from intact islets at a substimulatory concentration (2 mM) of glucose, which was not dependent upon the presence of extracellular Ca²⁺. MP also stimulated ATP-independent insulin secretion from electrically permeabilised islets in which intracellular Ca²⁺ was clamped at a substimulatory concentration (50 nM). MP-induced insulin secretion was not inhibited by down-regulation of islet protein kinase C, nor by the protein kinase inhibitor staurosporine, nor by the cyclic AMP antagonist Rp-adenosine 3′,5′-cyclic phosphorothioate. However, MP-induced secretion from permeabilised islets was inhibited by the presence of guanosine 5′-O-2-thiodiphosphate. These results suggest that MP stimulates insulin secretion by a mechanism that is independent of changes in cytosolic Ca²⁺ or protein kinase activation, but which is dependent, at least in part, upon activation of a GTP-binding protein at a late stage in the secretory process.

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The next series of studies were aimed at examining the effects of mastoparan, a tetradecapeptide from wasp venom, on histidine kinase activity and phosphorylation of the β subunit of trimeric G-proteins from isolated normal rat islets. The choice of mastoparan was based on the fact that it is a global activator of G-proteins, and it has been shown in several studies, including our own [18,19,24–26], that mastoparan stimulates exocytosis of insulin from isolated islets and clonal β cell preparations, involving G-proteins endogenous to β cells. Therefore, we examined the regulation by mastoparan of Gβ subunit phosphorylation and histidine kinase activity in rat islets.
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Mastoparan stimulates insulin secretion from pancreatic β-cells by effects at a late stage in the secretory pathway

Abstract

J. Biol. Chem.

Mol. Cell. Endocrinol.

Life Sci.

Neuroscience

FEBS Lett.

Biochim. Biophys. Acta

J. Biol. Chem.

FEBS Lett.

Prostaglandins, Leukotrienes and Essential Fatty Acids

Biochem. Biophys. Res. Commun.

Biochim. Biophys. Acta

J. Biol. Chem.

J. Biol. Chem.

FEBS Lett.

Biochem. Biophys. Res. Commun.

J. Mol. Endocrinol.

Biochim. Biophys. Acta