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Glucose-induced desensitization of the pancreatic β-cell is species dependent

Walter S. Zawalich, Marc Bonnet-Eymard, Kathleen C. Zawalich
1998 American Journal of Physiology. Endocrinology and Metabolism  
Zawalich, Walter S., Marc Bonnet-Eymard, and Kathleen C. Zawalich. Glucose-induced desensitization of the pancreatic ␤-cell is species dependent. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E917-E924, 1998.-The capacity of 20 mM glucose to desensitize insulin release was determined. A prior exposure to 20 mM glucose impaired the response of rat islets to subsequent restimulation. Compared with control islets, insulin secretory rates measured 25-30 min after the onset of 20 mM glucose
more » ... M glucose stimulation were reduced by 75%. Restimulation of glucose-desensitized islets with 20 mM glucose plus 500 nM forskolin resulted in a dramatic enhancement of both phases of secretion. In contrast to the desensitization of rat islets induced by prior 20 mM glucose exposure, mouse islets were immune to this adverse effect of the hexose. Prior exposure to 20 mM glucose had no adverse effect on glucose usage rates. The activation of phospholipase C in glucose-desensitized rat islets was compromised when compared with control islets. The impairment could not be accounted for by a decrease in immunoreactive content of several major phospholipase C isozymes (␤1 or ␦1) or their partitioning between the membrane and cytosolic compartments. In contrast to rat islets, prior exposure of mouse islets to 20 mM glucose for 180 min had no effect on inositol phosphate accumulation. These observations document an additional difference between rat and mouse islets and suggest that the evolution of desensitization is a consequence of the impaired activation of phospholipase C in rat islets. phospholipase C; inositol phosphates; toxicity; islets The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
doi:10.1152/ajpendo.1998.275.6.e917 fatcat:f6sxt2hsqvgvlia57k3o43ml6u