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Summary. Diabetes mellitus is held to be accompanied by inappropriately high levels of plasma glueagon relative to blood glucose concentrations. This has been interpreted as indicating lack of insulin. To establish ghcagon release in presence of high levels of endogenous insulin, the effects of both glucose and arginine were studied in the isolated perfused pancreas of genetically diabetic mice (db/db). Stimulation with glucose 2.75 mM or glucose plus arginine 8.25 mM exhibited a pronounced hyperglueagonemia. Following glucose 8.25 raM, however, there was no depression of glucagon secretion. Despite excessive high levels of endogenous insulin, there was a pattern of rather non-suppressible glueagon release. Lack of insulin per se, therefore, is unlikely to be the sole cause of hyperglucagonemia in this type of genetic animal diabetes mellitus.Key words : Diabetic mice, isolated perfused pancreas, high insulin levels, hyperglucagonemia.Patients with inherited diabetes mellitus are said to demonstrate increased pancreatic glueagon release relative to blood sugar levels [25,16]. Extremely high levels of glueagon have also been reported in alloxan treated dogs [17], streptozotoein diabetic rats [13] and in patients with severe ketoacidosis [1]. This has been interpreted as a state of decreased suppressibility of the alpha cell in the diabetics, probably on the base of lack of insulin. Infusion of insulin in animals with artificially achieved diabetes corrected instantly the state of hyperglucagonemia.Recent studies-in diabetic patients, however, exhibited only a slow and modest decline of glueagon after infusion of high insulin dosages. It was, therefore, concluded that mere lack of insulin may not adequately explain the alpha cell abnormality in diabetes mellitus [26]. Most of these patients, however, were receiving tolbutamide, and exhibited a markedly decreased insulin release following a carbohydrate meal compared to non diabetic controls.The present report deals with the alpha cell function in diabetic mice. The isolated perfused mouse pancreas was examined. Due to the hyperinsulinism in these obese animals the effect of high endogenous insulin release on pancreatic glueagon secretion was examined. Material and MethodsFor the present experiments diabetic mutant mice (C 57 BL/Ks-db/db ; Jackson Laboratory, Bar Harbour, Maine, USA), weighing 50--60 g, approximately 2--3 months old, and lean litter controls were used. Each group consisted of 5 animals.The mice were operated on after a 6 h fast. The pancreas was dissected under sodium pentobarbital anesthesia in a way similar to that already described for rats [23]. Arterial flow was achieved by cannulation * Supported by Deutsche Forschungsgemeinsehaft, Bad Godesberg. of the thoracic aorta. The perfusion medium consisted of an Umbreit buffer supplemented with 1% albumin (Fa. Behring Werke, Marburg) and equilibrated with 95% O2: 5% C02. The FFA content of the albumin buffer was < 50/~Lva]/1. A constant flow rate of 1 ml/ min was achieved by a pressure of about 40 m...

Experimental diabetes was produced in rats by i.v. streptozotocin injection (65 mg/kg). There was a significant increase in blood glucose and serum glucagon, while there was a significant d~crease in serum insulin in diabetic animals as compared with controls. It is oe interest that the glucagon elevation in the streptozotocin-induced diabetes in animals is of comparable magnitude to that seen in the ketoacidotic state of human diabetes.