Significance of Extrapancreatic Glucagon in Diabetes Mellitus

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In order to elucidate the significance of extrapancreatic glucagon in diabetes mellitus, experimental and clinical investigations were performed. In the present study, plasma glucagon and total immunoreactive glucagon were measured using an antiserum (G-21) specific for pancreatic glucagon and a non-specific antiserum (G-25), respectively. In a series of experiment with conscious dogs, 30 ml of 10% arginine were administered into the crural vein and blood samples were obtained from the peripheral vein on the other side. Alloxan diabetic dogs revealed not only elevated fasting levels of plasma glucagon but also exaggerated glucagon response to arginine. Insulin treatment in the alloxan diabetic dogs reduced the fasting plasma glucagon levels as well as responsiveness of glucagon to arginine. In the experiments with anesthetized dogs, 60 ml of 10% arginine solution were infused for 10 min before and after total pancreatectomy. Before pancreatectomy, plasma glucagon increased in the normal dogs and alloxan diabetic dogs, whereas that in the alloxan diabetic dogs treated with insulin rose slightly in response to arginine infusion. After total pancreatectomy, plasma glucagon in the portal vein of the normal dogs rose only slightly in response to arginine. In contrast, the alloxan diabetic dogs revealed an increase in plasma glucagon following arginine infusion performed after pancreatectomy. The response of plasma glucagon to arginine was reduced after pancreatectomy in the alloxan diabetic dogs with insulin treatment. Total immunoreactive glucagon increased slightly following arginine infusion before pancreatectomy in the three experimental groups. In the alloxan diabetic dogs, however, it increased markedly in response to arginine infused after pancreatectomy. Here insulin treatment reduced an exaggerated response of total immunoreactive glucagon in alloxan diabetic dogs. In addition, the results obtained in the present study suggest that gut glucagon-like immunoreactivity, which was calculated by subtraction of glucagon from total immunoreactive glucagon, revealed an elevated response to arginine in diabetic states. In two patients with total pancreatectomy and treated with insulin, no increase in plasma glucagon was observed during an arginine infusion test at all, corresponding to the results in the alloxan diabetic dogs with insulin treatment.<BR>From the present experiment it is concluded that alloxan diabetic dogs revealed an increased response of plasma glucagon and extrapancreatic glucagon, which was reduced by insulin treatment.
Japan Society of Clinical Chemistryの論文

Significance of Extrapancreatic Glucagon in Diabetes Mellitus

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