Glucose-induced desensitization of the pancreatic beta-cell is species dependent.
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 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 (beta1 or delta1) 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.
Zawalich
W S
WS
Yale University School of Nursing, New Haven, Connecticut 06536-0740, USA.
Bonnet-Eymard
M
M
Zawalich
K C
KC
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004338:Drug Combinations; D005947:Glucose / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice / Q000378:metabolism; D008815:Mice, Inbred Strains; D051381:Rats / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D010738:Type C Phospholipases / Q000378:metabolism
D004338:Drug Combinations; D007295:Inositol Phosphates; D007328:Insulin; D007527:Isoenzymes; D005576:Colforsin; D010738:Type C Phospholipases; D005947:Glucose