Simulation of the normal glucopenia-induced decline in insulin partially restores the glucagon response to glucopenia in isolated perfused pancreata of streptozotocin-diabetic rats.
To determine if the loss of the glucagon response to glucopenia that follows destruction of beta cells is at least in part a consequence of the absence of the normal glucopenia-induced decline in insulin secretion, pancreata from insulin-requiring streptozotocin-diabetic rats were studied. In the absence of insulin, a reduction in perfusate glucose concentration from 150 to 25 mg/dl failed to elicit a rise in glucagon concentration. When insulin was co-perfused at 30 mU/ml, the estimated within-islet concentration of insulin under these circumstances, but discontinued during the glucopenic interval, reducing the insulin concentration in the pancreatic venous effluent from approximately 26 mU/ml to less than 100 microU/ml, a prompt and significant rise in glucagon was observed until glucose and insulin levels were raised to their original concentrations. The rise in glucagon, which was approximately 25% of the normal response, did not occur when insulin concentration in the perfusate was maintained at 30 mU/ml during the glucopenic period. Nor did it occur when insulin was perfused at 360 microU/ml and discontinued during the glucopenic period, thereby lowering insulin in the venous effluent from 300 microU/ml to 5 microU/ml. It is concluded that the decline in insulin from its normal concentrations within the islets makes a modest but significant contribution to the rise in glucagon that occurs during glucopenia.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D005934:Glucagon; D005947:Glucose