Non-insulin-dependent diabetes mellitus is associated with loss of
pancreatic [beta]-cell l-type ca2+ channel activity.
Roe, Michael W., Jennings F. Worley, Iii, Yoshiharu Tokuyama, Louis H.
Philipson, Jeppe Sturis, Jiping Tang, Iain D. Dukes, Graeme I. Bell,
and Kenneth S. Polonsky.
Section of Endocrinology, Department of Medicine, and Howard Hughes
Medical Institute, University of Chicago, 5841 S. Maryland Ave. MC
1027, Chicago, IL 60637, Department of Cell Physiology, Glaxo
Research Institute, 5 Moore Dr., Research Triangle Park, NC 27709
APStracts 2:0189G, 1995.
Development of non-insulin-dependent diabetes mellitus (NIDDM) is
associated with defects in glucose-stimulated insulin secretion. We
have investigated Zucker diabetic rats (ZDF), an animal model of
NIDDM, and found, in comparison with control islets, that the
expression of mRNA encoding C- and D-isoforms of [alpha]1-subunits of
[beta]-cell L-type voltage-dependent Ca2+ channels (VDCC) was
significantly reduced in islets isolated from ZDF rats. This
correlated with a substantial reduction of L-type Ca2+ currents (ICa)
in ZDF [beta]-cells. Intracellular Ca2+ concentration responses in
ZDF islets following glucose, KCl, or BAY K8644 stimulation were
markedly attenuated, whereas, responses evoked by carbachol were
unimpaired, consistent with a specific decrease in ICa in the
diabetic islets. This reduction was accompanied by loss of pulsatile
insulin secretion from ZDF islets treated with oscillatory increases
of external glucose concentration. Our findings suggest that the
attenuation of ICa in diabetic islets may contribute to the abnormal
glucose-dependent insulin secretory responses associated with NIDDM,
and indicate that this defect is caused by decreased expression of
genes encoding [beta]-cell VDCC [alpha]1-subunits.
Received 9 June 1995; accepted in final form 7 August 1995.
APS Manuscript Number G265-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95