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.
Gross
R
R
Faculty of Medicine, Pharmacology Laboratory, Unité de Recherche Associeé 599 du Centre National de la Recherche Scientifique, Montpellier, France.
Hillaire-Buys
D
D
Bertrand
G
G
Ribes
G
G
Loubatieres-Mariani
M M
MM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000098:blood supply*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects
D007328:Insulin; D005934:Glucagon; D000241:Adenosine