Summary
In order to investigate the relationship between the development of diabetes mellitus
and glucagon, experimental studies were performed in genetically diabetic mice (KKAy 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.
Key-Words:
KK B1 Mice
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KKAy Mice
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Insulin
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Glucagon
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Gastric Glucagon
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Gut GLI