Insulin release and pancreatic insulin is reduced in young prediabetic BB rats

The pancreases of approximately 50 days old diabetes-prone BB/Hagedorn (BB/H) and of the genetically closely related, but non-diabetic BB w-subline (control BB) rats were perfused to determine the capacity of D-glucose to release insulin before the expected development of diabetes. The BB/H rats were from a colony with 82-84% incidence of insulin-dependent diabetes mellitus (IDDM) by 140 days of age. The total amount of insulin released from the BB/H rat pancreas during stimulation with 20 mmol/1 mmol/ D-glucose was reduced by nearly 50% (P less than 0.01). The initial peak of insulin release was similar between the two groups of animals, whereas the amount of insulin released during the second peak accounted for the diminished release (P less than 0.01). The extractable pancreatic insulin was 30% (P less than 0.05) less in the BB/H rats. Total insulin release expressed relative to the pancreatic insulin content, was therefore not different between the two groups. It is concluded that about 20-40 days before the mean age of clinical onset of IDDM in BB/H rats, the capacity to release insulin in response to D-glucose is reduced along with a diminished pancreatic insulin content. This abnormality seems to be preceded only by islet cell surface antibodies but not by insulitis.