SEARCH

SEARCH BY CITATION

Keywords:

  • islet amyloid polypeptide;
  • islet amyloid protein;
  • patch clamp technique;
  • islet beta cells;
  • high voltage-gated calcium channel

Abstract

Objective

The mechanism by which islet amyloid polypeptide (IAPP) inhibits insulin release is unclear. We hypothesized that reduced voltage-gated calcium channel activity and intracellular Ca2+ concentration might contribute to IAPP-mediated inhibition of glucose-stimulated insulin release.

Research design and methods

Rat islet beta cells were cultured and treated with various extracellular concentrations of IAPP, and insulin release was stimulated via addition of glucose. Activation voltage, high voltage-gated calcium channel currents, intracellular Ca2+ concentration, and insulin secretion were detected by patch clamp electrophysiology, fluorescent digital imaging microscopy using calcium-sensitive fluorescent dye, and radioimmunoassay, respectively.

Results

High voltage-gated calcium channel currents, intracellular Ca2+ concentration, and insulin secretion increased in a dose-dependent manner when rat beta cells were exposed to glucose. After short-term IAPP treatment (5 or 10 µM), these parameters decreased significantly in glucose-stimulated beta cells. However, no significant changes were observed with lower doses of IAPP.

Conclusions

Glucose-stimulated islet beta-cell high voltage-gated calcium channels were activated in conjunction with insulin secretion, while high extracellular concentrations of IAPP inhibited beta-cell high voltage-gated calcium channel activation and insulin secretion in a dose-dependent manner. Copyright © 2010 John Wiley & Sons, Ltd.