[Effects of a long-acting adenosine analogue on insulin and glucagon release (author's transl)]

The adenosine analogue 765-21 (10 micrograms/kg intravenously), substituted at the 5'-position, caused a sustained increase in plasma glucose and a decrease in plasma free fatty acid concentrations in conscious dogs. Concomitantly, plasma glucagon levels rose threefold. Changes in plasma insulin concentration were relatively small and of no statistical significance. A simultaneous fall in arterial blood pressure was also observed. Aminophylline, an adenosine antagonist, inhibited the haemodynamic as well as the metabolic responses evoked by the adenosine analogue. - In collagenase-isolated rat islets of Langerhans 765-21 inhibited glucose-induced insulin release in a dose-dependent manner (concentration range 10(-8) to 10(-5) M). In contrast to the data obtained on conscious dogs, 765-21 did not promote glucagon release from the pancreatic islets. Since stimulation of glucagon secretion was also not observed on decreasing the glucagon concentration in the incubation medium, the collagenase technique of isolation may be responsible for the insensitivity of the islets to glucagon-releasing stimuli. - The results are indicative of a specific inhibition of glucose-induced insulin release by 765-21. The data obtained in vivo additionally suggest a glucagon-releasing activity of the adenosine analogue investigated.