Endocrinology, Vol 130, 3135-3142, Copyright © 1992 by Endocrine Society

ARTICLES

Glucosamine-induced desensitization of beta-cell responses: possible involvement of impaired information flow in the phosphoinositide cycle

WS Zawalich and KC Zawalich
Yale University School of Nursing, New Haven, Connecticut 06536-0740.

The influence of glucosamine on beta-cell response characteristics of collagenase-isolated rat islets was determined. Groups of islets were incubated for 2 h with myo-[2-3H]inositol to label their phosphoinositide (PI) pools. Also included in some experiments was glucosamine (0.1-10 mM). Subsequently, these islets were perifused, and their responses to 10 mM glucose, 10 mM alpha-ketoisocaproate (KIC), and 1 microM of the phorbol ester phorbol 12-myristate 13-acetate were assessed. Increases in PI hydrolysis were monitored during the perfusion by measuring fractional efflux rates of [3H]inositol. The accumulation of inositol phosphates after the perifusion was also determined. In other experiments, the use of 10 mM glucose was measured after a 2-h exposure to 5 or 10 mM glucosamine. Finally, the ability of glucosamine itself to augment release and activate PI hydrolysis was assessed. The following observations were made. 1) A prior 2-h exposure to 5-10 mM glucosamine resulted in parallel dose-dependent impairments in 10 mM glucose-induced insulin release and PI hydrolysis. 2) Glucosamine (5-10 mM) also impaired the subsequent response to alpha- ketoisocaproate (KIC). Parallel deficits in KIC-induced PI hydrolysis were noted under conditions where insulin secretion was impaired. 3) Under several conditions where glucosamine impaired glucose-induced secretion, it had no adverse effect on phorbol 12-myristate 13-acetate- induced release. 4) The desensitizing effect of 10 mM glucosamine on 10 mM glucose-induced release and PI hydrolysis developed within 30 min of exposure to it. 5) Glucosamine (5-10 mM) preexposure had no adverse effect on the use of 10 mM glucose by desensitized islets. 6) Short term (5-min) exposure to glucosamine (10 mM) alone stimulated PI hydrolysis, while a 30-min exposure to the same level of the hexosamine depressed it. 7) In the presence of 0.25 microM forskolin, 10 mM glucosamine also had a transient stimulatory effect on insulin release. These findings support the concept that the acute and chronic effects of glucosamine on the beta-cell result at least in part from its ability to influence PI hydrolysis in islets.

This article has been cited by other articles:

				H. Yamazaki, K. C. Zawalich, and W. S. Zawalich Desensitization of the pancreatic beta-cell: effects of sustained physiological hyperglycemia and potassium Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): H1381 - H1387. [Abstract] [Full Text] [PDF]

				R. C. Cooksey, S. Pusuluri, M. Hazel, and D. A. McClain Hexosamines regulate sensitivity of glucose-stimulated insulin secretion in {beta}-cells Am J Physiol Endocrinol Metab, February 1, 2006; 290(2): E334 - E340. [Abstract] [Full Text] [PDF]

				H. Yamazaki, W. Philbrick, K. C. Zawalich, and W. S. Zawalich Acute and chronic effects of glucose and carbachol on insulin secretion and phospholipase C activation: studies with diazoxide and atropine Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E26 - E33. [Abstract] [Full Text] [PDF]

				W. S. Zawalich, M. Bonnet-Eymard, and K. C. Zawalich Glucose-induced desensitization of the pancreatic beta -cell is species dependent Am J Physiol Endocrinol Metab, December 1, 1998; 275(6): E917 - E924. [Abstract] [Full Text] [PDF]