Inhibition of insulin release by enterostatin

Abstract

OBJECTIVE: These studies were designed to investigate the mechanism through which enterostatin inhibits insulin secretion from pancreatic islets.

DESIGN: A static islet incubation method was used to study the effects of enterostatin on insulin secretion induced by various secretagogues and to investigate the effect of calcium ions and 8-Br-cyclic AMP on the response to enterostatin. Measurements of islet cAMP concentrations in response to enterostatin were also made.

RESULTS: Enterostatin (10⁻⁹ to 10⁻⁵ M) inhibited insulin secretion from islets incubated in the presence of 16.7 mM glucose in a dose-dependent manner. Enterostatin also inhibited insulin secretion stimulated by glybenclamide (5.0 and 10 μM), phorbol 12-myristate-13-acetate (TPA) (50 and 100 nM), and the kappa-opioid agonist U50,488 (100 nM). The inhibitory effect of enterostatin on TPA-induced insulin secretion was attenuated but still remained in the absence of extracellular Ca²⁺. The enterostatin inhibition of insulin secretion was blocked by 8-Br-cAMP (1 mM) independent of extracellular Ca²⁺. Enterostatin reduced the increase in intracellular cyclic AMP (cAMP) content produced by U50,488 (100 nM) and the changes in cAMP content were parallel with changes in insulin release.

CONCLUSION: Enterostatin may suppress insulin secretion through the reduction of cAMP, but other mechanisms may also be possible.