Diabetes and impaired response of glucagon cells and vascular bed to adenosine in rat pancreas.

Previous studies have shown that adenosine, by activation of purinergic A2-receptors, stimulates glucagon secretion and increases vascular flow rate in isolated perfused pancreases from nondiabetic rats. Because alpha-cell function and blood flow control are known to be disturbed in diabetes, we investigated whether adenosine was still effective in streptozocin-induced diabetic (STZ-D) rats. Our experiments were performed on isolated perfused rat pancreases. Whereas, in normal rats, adenosine (1.65 microM) induced a 200% increase in glucagon output and a 25% rise in the pancreatic vascular flow rate, in rats diabetic for 5-6 wk, this nucleoside was ineffective on glucagon secretion, and its vasodilatory effect was strongly reduced. Long-term in vivo insulin treatment that reversed high glycemia levels was able to restore in large part both adenosine effects. In contrast, a short-term in vitro pretreatment with insulin was unable to restore the nucleoside effects. We conclude that STZ-D suppresses the stimulatory effect of adenosine on alpha-cells and strongly reduces its vasodilator properties; these abnormalities may be corrected in large part by long-term insulin treatment with normalization of glycemia.