Reduced beta-cell mass and altered @entity413 sensing impair insulin-secretory function in betaIRKO XXXX .

@entity6 @entity19 @entity73 @entity4338 @entity30006 @entity3239 @entity52378 @entity4854 @entity413 @entity41341
Pancreatic beta-cell-restricted knockout of the @entity3239 results in @entity4854 due to @entity73 , suggesting that this cell is an important target of insulin action. The present studies were undertaken in beta-cell @entity3239 knockout (betaIRKO) @entity19 to define the mechanisms underlying the defect in insulin secretion. On the basis of responses to intraperitoneal @entity413 , approximately 7-mo-old betaIRKO @entity19 were either @entity6 (25%) or normally @entity413 tolerant (75%). Total insulin content was profoundly reduced in pancreata of mutant @entity19 compared with controls. Both groups also exhibited reduced beta-cell mass and islet number. However, insulin mRNA and protein were similar in islets of @entity6 and normoglycemic betaIRKO @entity19 compared with controls. Insulin secretion in response to insulin secretagogues from the isolated perfused pancreas was markedly reduced in the @entity6 and to a lesser degree in the nondiabetic betaIRKO group. Pancreatic islets of nondiabetic betaIRKO animals also exhibited defects in @entity30006 - and @entity4338 -stimulated insulin release that were milder than in the @entity6 animals. Gene expression analysis of islets revealed a modest reduction of @entity41341 and @entity52378 gene expression in both the nondiabetic and @entity6 mutants. Taken together, these data indicate that loss of functional receptors for insulin in beta-cells leads primarily to profound defects in postnatal beta-cell growth. In addition, altered @entity413 sensing may also contribute to defective insulin secretion in mutant animals that develop @entity6 .
