DEVELOPMENT OF THE INSULIN SECRETORY DEFECT IN GENETICALLY DIABETIC (db/db) MOUSE

Abstract

Genetically diabetic mice (C57BL/KsJ-db/db) were used as a model to study the development of defects of insulin secretion in relation to common metabolic indicators (body weight, serum glucose and insulin and islet insulin content). Consistent with the idea of a protective effect of estrogen on the pancreatic .beta.-cell, the female diabetic mice survived longer than the males. In males, while serum insulin decreased in the later stages of the disease, serum glucose increased progressively with age. Perfusion of the diabetic pancreas revealed a rise and subsequent fall with age of the basal insulin released at 3 mM glucose. Despite previous reports of .beta.-cell hyperplasia, progressive impairment of the insulin response to 20 mM glucose or to 20 mM glucose and 1 mM 3-isobutyl-1-methylxanthine, was seen with increasing age in experiments with perfused pancreas or microdissected islets. Islet content of insulin also decreased progressively with age in the diabetic animals.