Altered Functions of Ion Channels in Diabetic β Cells

Abstract

Selective impairment of glucose‐induced insulin secretion and hyper‐responsiveness to arginine are known features of GK rats, a genetic model of NIDDM. We focus on the ionic mechanism underlying these phenomena using patch‐clamp techniques. Pancreatic islets were isolated from male GK rats and age‐matched control Wistar rats and were subjected to dispersion and culture. Single channel recordings of KATP cnannels were performed using either on‐cell mode or inside‐out patch mode. Ca2+ channel currents were recorded under conventional whole‐cell mode. In GK β cells, ATP sensitivity of KATP channels itself was not altered, although glucose‐induced closure of KATP channels was severely impaired. Among substrates for fuel metabolism, only dehy‐droxyacetone (DHA) reproduced this anomaly. On the other hand, current densities of L‐type Ca2+ channels were increased in GK β cells. Since DHA is a known substrate for glycerol phosphate shuttle, current data suggest that major metabolic deficit of GK β cells resides in this shuttle. On the other hand, increased L‐type Ca2+ channel activities might be an ionic basis for augmented insulin response to non‐glucose depolarizing stimuli in GK β cells. 1995 North American Association for the Study of Obesity (NAASO)