Summary
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.
Key-Words
C-peptide
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Insulin
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Glucose
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Obese Hyperglycaemic (ob/ob) Mice
