Dynamic Time-Course Studies of the Spontaneously Diabetic BB Wistar Rat. II. Insulin-, Glucagon-, and Somatostatin-Reactive Cells in the Pancreas*

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Abstract
The effects of spontaneous diabetes on pancreatic A, B, and D cells were assessed using immunocytochemical, and histochemical RIA techniques. Three groups of untreated diabetic BB Wistar rats were studied at various stages of the diabetic syndrome: 1) early diabetes (1–3 days post detection of glycosuria), 2) unstable diabetes (end stage; 7–22 days post detection), and 3) stable diabetes (41–63 days post detection). Their data were compared to those of nondiabetic control littermates. The pancreatic immunoreactive insulin (IRI) concentration was severely reduced to less than 3% as early as 1 day post detection. The unstable form of diabetes was characterized by significantly decreased immunoreactive concentrations of all three pancreatic hormones, including glucagon (IRG) and somatostatin (IRS). The stable form differed from the unstable form in having slightly higher pancreatic IRI concentrations and significantly greater IRG and IRS concentrations. The loss of B cells was evident at allstages of diabetes. The number of A and D cells appeared normal in stable diabetics, but was reduced in unstable diabetics. Histological examination of pancreatic islets from a group of young normoglycemic BB rats revealed variable degrees of insulitis, indicating that the destructive process in the pancreas is initiated well in advance of the clinical disease. Despite wide variation in pancreatic hormone concentrations in these animals, significant positive correlations were observed among pancreatic IRI, IRG, and IRS concentrations, suggesting differences in initial islet cell mass between animals. Furthermore, the results suggest that the A and D cells in the unstable form of diabetes may have been affected by the same process which destroyed the B cells, or that the integrity of the A and D cells is dependent on a minimal local concentration of insulin.