Immunoreactive C-peptide in spontaneous syndromes of obesity and diabetes in mice.
Immunoreactive C-peptide was evaluated in the plasma and pancreas of Aston ob/ob and C57BL/KsJ db/db mice in relation to disturbances in pancreatic B-cell function. At 18-24 weeks of age, ob/ob and db/db mice displayed hyperglycaemia (1.6 and 3.8 fold increases respectively) and hyperinsulinaemia (10.8 and 5.1 fold increases respectively) despite a similar pancreatic insulin content to their respective non-diabetic lean control mice. Immunoreactive C-peptide concentrations in the plasma and pancreas of the mutants corresponded with the degree of hyperinsulinaemia and pancreatic insulin content, and the insulin: C-peptide molar ratios in both mutants were similar to lean controls. In ob/ob mice parenteral glucose administration decreased plasma insulin and C-peptide concentrations, despite markedly raised glucose concentrations. However, administration of a low dose of insulin (5 U/kg) to lean mice and much higher doses of insulin (50 and 120 U/kg) to ob/ob mice markedly decreased plasma glucose and C-peptide concentrations. When the rate and extent of insulin-induced glucose suppression observed in ob/ob mice was mimicked in lean mice, an almost complete (95%) inhibition of C-peptide was achieved compared with a 57% decrease in the ob/ob mutant. Injection of ob/ob mice with glucose to counter the insulin-induced hypoglycaemia failed to affect the fall of C-peptide concentrations. The data suggest that the metabolic processing of insulin and C-peptide are undisturbed in obese-diabetic mice, and that the impaired suppression of circulating C-peptide by insulin-hypoglycaemia in ob/ob mice predominantly reflects impaired feedback inhibition by insulin.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000032:analysis* / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000032:analysis / Q000097:blood; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D009765:Obesity; D011863:Radioimmunoassay
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005947:Glucose