Endocrine pancreas in insulin receptor-deficient mouse pups

Insulin receptor (IR)-deficient pups rapidly become hyperglycemic and hyper insulinemic and die of diabetic ketoacidosis within a few days. Immunocytoc hemical analysis of the endocrine pancreas revealed that IR deficiency did not alter islet morphology or the number of beta-, alpha-, delta-, and panc reatic polypeptide (PP) cells. The lack of IR did not result in major chang es in the expression of islet hormone genes or of beta -cell-specific marke r genes encoding pancreas duodenum homeobox-containing transcription factor -1 (PDX-1), glucokinase (GCK), and GLUTS, as shown by reverse transcriptase -polymerase chain reaction analysis. The serum glucagon levels in IR-defici ent and nondiabetic littermates were comparable. Finally, total insulin con tent in the pancreas of IR-deficient pups was gradually depleted, indicatin g sustained insulin secretion, not compensated for by increased insulin bio synthesis. These findings are discussed in light of recent results suggesti ng a role of IR in beta -cell function.