Loss of a priming effect of glucose on A and D cell secretion in perfused pancreases from alloxan-diabetic rats: role of insulin and alloxan.
Under normal conditions, glucose acutely influences pancreatic islet B, A and D cell secretion. In addition, prior exposure to glucose modulates the secretory responsiveness of these cells (priming effect). We have tested whether alloxan diabetes influences priming effects of glucose on A and D cell secretion. Rat pancreases were perfused 72 h after alloxan treatment. A 20 min infusion of 27.7 mmol/l of glucose failed to induce priming effects, i.e. it did not inhibit the glucagon nor amplify the somatostatin response to a subsequent (15 min later) infusion of 8 mmol/l of arginine. Insulin treatment in vivo for 48 h restored a priming effect of glucose on glucagon secretion in the perfused pancreas, i.e. exposure to 27.7 mmol/l of glucose now inhibited subsequent arginine-induced glucagon secretion by 48% relative to a stimulation period with arginine preceding the glucose pulse (from 5.0 +/- 0.7 to 2.6 +/- 0.5 ng/min, p less than 0.01). Conversely, insulin treatment in vivo did not restore a priming effect of glucose on somatostatin secretion. Other effects noted were failure of 27.7 mmol/l glucose to stimulate, during its presence, the release of somatostatin from pancreases of the diabetic rats whether untreated or insulin-treated. Furthermore, insulin treatment abolished the arginine-induced somatostatin secretion observed in pancreases from untreated rats. It is concluded that short-term alloxan diabetes leads to loss of a priming effect of glucose on glucagon secretion and that this abnormality is secondary to direct or indirect effects of insulinopenia. Concomittant abnormalities of glucose regulation of somatostatin secretion may, in part, be secondary to a cytotoxic effect of alloxan on the D cell.
D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010187:Pancreatic Hormones / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism
D007328:Insulin; D010187:Pancreatic Hormones; D013004:Somatostatin; D000496:Alloxan; D005934:Glucagon; D001120:Arginine; D005947:Glucose