Paradoxical glucagon response in perifused islets of the diabetic Chinese hamster

Dynamic insulin and glucagon response to glucose was examined in the perifusion system to investigate the relationship between pancreatic hormone content and the pattern of hormone secretion in diabetic Chinese hamsters of the Asahikawa colony (CHA). Isolated islets of normals and diabetics from the CHA were perifused. When the medium was changed to high glucose (500 mg/dl), a low insulin response and paradoxical glucagon response were seen in diabetics compared with normals. Positive correlations were found between pancreatic insulin and the amount of perifusate insulin, and glucagon content and glucagon release, respectively. It is suggested, accordingly, that pancreatic hormone content is related to the amount of hormone release in CHA. A negative correlation between the amount of perifusate insulin and glucagon release was found. It is suggested, therefore, that an impaired suppression of glucagon release in the diabetic CHA animals could be attributed at least to insulin deficiency. These findings agree with the histological discovery of decreased B-cells and increased A-cells in the diabetic islets. Both decreased B-cells and islet numbers could be the cause of the low insulin response to glucose. Increased numbers of A-cells with hyperfunction resulting from local insulin deficiency could be the cause of the paradoxical glucagon response.