Changes in the pancreatic A-, B- and D-cell populations during development of diabetes in spontaneously diabetic Chinese hamsters of the Asahikawa colony (CHAD)

Abstract

We investigated the pathological changes in pancreatic islets during the development of diabetes in spontaneously diabetic Chinese hamsters of the Asahikawa colony (CHAD), using morphometric analysis and specific immunocytochemical methods. We also investigated the relationships between changes in islet cell composition and the hormonal changes in the plasma and pancreas. Plasma and pancreatic insulin levels were significantly lower in diabetic hamsters than in pre-diabetic hamsters. However, plasma insulin levels in the pre-diabetic hamsters were significantly higher than those in the hamsters from the non-diabetic control strain, although the pancreatic insulin content in the pre-diabetics was significantly lower than that in the non-diabetics. Since even a severely diabetic CHAD is alive for many months after the onset of the disease without injections of insulin, its clinical course seems to be close to that of type 2 human diabetes. In contrast, plasma and pancreatic glucagon levels were significantly higher in diabetic hamsters than in non-diabetics and pre-diabetics. There were significantly positive correlations between plasma and pancreatic insulin, and plasma and pancreatic glucagon levels in CHAD (P less than 0.01). On the other hand, no significant differences in the pancreatic somatostatin content were found among the non-diabetics, pre-diabetics, and severe diabetics. Significant correlations were found between plasma and pancreatic hormone levels (except for somatostatin) and the advance of diabetes in CHAD (P less than 0.01). Morphometric analysis by planimeter revealed that islets in the severe diabetics were 25% smaller than in the pre-diabetics. Significantly less B-cell area within the diabetic islets was found when compared with the non-diabetic and pre-diabetic islets. Significantly larger A- and D-cell areas within the diabetic islets were found compared with the non-diabetic and pre-diabetic islets. There was a significant correlation between the areas of the three types of cell within the islets and the severity of diabetes (P less than 0.01). It is suggested, therefore, that the pancreatic islet function in CHAD is closely associated with the morphologic changes in islet endocrine cells. The elevation of plasma and pancreatic glucagon levels and the marked increase of the A-cell area within the islets from severely diabetic CHAD may reveal an absolute increase of A-cell numbers.