Absence of glucopenic inhibition of the insulin response to arginine at the onset of diabetes in BB/W rats.

To determine if the inhibiting effect of glucopenia on arginine-stimulated insulin secretion is impaired at the onset of autoimmune diabetes, the insulin response to arginine was studied at 5.6 and 2.8 mmol/l glucose in perfused pancreata isolated from BB/W rats on the first day of diabetes and from age-matched diabetes-prone BB/W rats without diabetes. During glucopenia the baseline insulin secretion was reduced by more than 80% in both groups. However, the arginine-stimulated insulin response in the diabetic group was only 16.5% lower during glucopenia compared to 79.1% lower in the nondiabetic controls. Also, enhancement of the arginine-stimulated glucagon response by glucopenia was modest compared to controls. The results indicated that at the onset of this form of autoimmune diabetes the surviving B cells are, for unknown reasons, hyperresponsive to arginine and that, in contrast to the controls, this response is not inhibited by glucopenia.