Persistently enhanced sensitivity of pancreatic islets from ob/ob
mice to pkc-stimulated insulin secretion.
Chen, Neng-Guin, and Dale R. Romsos.
Department of Food Science and Human Nutrition, Michigan State
University, East Lansing, MI 48824-1224
APStracts 3:0208E, 1996.
Islets from 2-wk-old ob/ob and lean littermate mice were cultured for
4 to 12 days and then perifused or statically incubated to identify
early-onset differences in their regulation of insulin secretion.
Islets from these young ob/ob and lean mice increased insulin
secretion similarly in response to glucose (10 or 20 mM) whereas
responsiveness to glucose plus acetylcholine (10 [mu]M) was greater
in islets from ob/ob mice than lean mice. This phenotype-specific
effect of acetylcholine was mimicked by phorbol-12-myristate-13
-acetate (PMA, 100 nM), a protein kinase C (PKC) agonist, whereas
prior down-regulation of PKC abolished this phenotype-specific effect
of acetylcholine. A high concentration of PMA (1 [mu]M) equally and
substantially increased insulin secretion from islets of ob/ob and
lean mice, suggesting an enhanced regulatory sensitivity rather than
altered responsiveness of the PKC system in islets of ob/ob mice.
Addition of BAY K8644, a Ca2+ channel agonist, to the perifusate
enhanced acetylcholine-induced insulin secretion from islets of lean
mice to attain the high rates observed by islets from ob/ob mice
exposed to acetylcholine alone. We propose that acetylcholine-induced
PKC regulation of insulin secretion is altered in islets from ob/ob
mice, that this alteration may directly or indirectly involve Ca2+
channels, and that it persists even when islets are cultured for up
to 12 days.
Received 13 August 1996; accepted in final form 13 September
1996.
APS Manuscript Number E390-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996