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Glucose-dependent and -independent electrical activity in islets of Langerhans of Psammomys obesus, an animal model of nutritionally induced obesity and diabetes.

Abstract：

:Glucose-induced insulin secretion from pancreatic beta-cells involves metabolism-induced membrane depolarization and voltage-dependent Ca(2+) influx. The electrical events in beta-cell glucose sensing have been studied intensely using mouse islets of Langerhans, but data from other species, including models of type 2 diabetes mellitus (T2DM), are lacking. In this work, we made intracellular recordings of electrical activity from cells within islets of the gerbil Psammomys obesus (fat sand rat), a model of dietary-induced T2DM. Most islet cells from lean, non-diabetic sand rats displayed glucose-induced, K(ATP) channel-dependent, oscillatory electrical activity that was similar to the classic "bursting" pattern of mouse beta-cells. However, the oscillations were slower in sand rat islets, and the dose-response curve of electrical activity versus glucose concentration was left-shifted. Of the non-bursting cells, some produced action potentials continuously, while others displayed electrical activity that was largely independent of glucose. The latter activity consisted of continuous or intermittent action potential firing, and persisted for long periods in the absence of glucose. The glucose-insensitive activity was suppressed by diazoxide, indicating that the cells expressed K(ATP) channels. Sand rat islets produced intracellular Ca(2+) oscillations reminiscent of the oscillatory electrical pattern observed in most cells, albeit with a longer period. Finally, we found that the glucose dependence of insulin secretion from sand rat islets closely paralleled that of the bursting electrical activity. We conclude that while subpopulations of K(ATP)-expressing cells in sand rat islets display heterogeneous electrical responses to glucose, insulin secretion most closely follows the oscillatory activity. The ease of recording membrane potential from sand rat islets makes this a useful model for studies of beta-cell electrical signaling during the development of T2DM.

journal_name

Gen Comp Endocrinol

journal_title

General and comparative endocrinology

authors

Zimliki CL,Chenault VM,Mears D

doi

10.1016/j.ygcen.2008.12.017

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

193-201

issue

eissn

0016-6480

issn

1095-6840

pii

S0016-6480(08)00473-5

journal_volume

161

pub_type

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Glucose-dependent and -independent electrical activity in islets of Langerhans of Psammomys obesus, an animal model of nutritionally induced obesity and diabetes.