Glucagon in spontaneously diabetic KK mice

In order to investigate the relationship between the development of diabetes mellitus and glucagon, experimental studies were performed in genetically diabetic mice (KKA gamma and KK B1) and in C57 mice of various ages. In the KK mice, the fasting plasma glucose increased during the aging process and reached the maximum at 14 weeks. The fasting plasma insulin in the KK mice was significantly elevated during the aging process and continued to increase till 20 weeks of age. In contrast, an increase in the fasting plasma glucagon was observed only at the age of 4 weeks, although the plasma glucagon increased during the aging process. The content of the insulin in the pancreas of the KK mice was significantly higher than that of the C57 mice, continuing to increase during the aging process. the glucagon content of the pancreas increased during the aging process but no significant difference was observed between the KK mice and the control mice. The total immunoreactive glucagon in the jejunum measured by non-specific antiserum was slightly reduced in the KK mice at the age of 14 weeks, compared with the C57 mice. There was no difference in the glucagon content of the stomach between the KK mice and the C57 mice of various ages. The KK mice at 14 weeks showed an elevated plasma glucagon 30 min after glucose injection, compared with the C57 mice, which indicates a reduced suppression of glucagon in response to hyperglycemia in the KK mice. The plasma glucagon in the KK mice 30 min after arginine was slightly higher than in the control mice, although not significantly so. From these results it was concluded that the KK mice revealed an elevation of fasting plasma glucagon in the early stage of diabetes mellitus and a decrease in glucose-induced glucagon suppression at 14 weeks and that diabetes mellitus in the KK mice derived mainly from insulin resistance associated with hyperinsulinemia.