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The fasting hyperinsulinaemia characteristic of obesity is due to pancreatic hypersecretion and is accompanied by a corresponding increase in plasma C-peptide concentrations. The exaggerated plasma insulin and C-peptide responses to oral glucose in obese subjects which is greater for insulin than C-peptide suggests that the stimulated hyperinsulinaemia is due to both pancreatic hypersecretion and decreased fractional hepatic extraction of insulin. In obese subjects fasting and stimulated insulin concentrations, but not those of C-peptide, are lower after 3 weeks of energy restriction than before it. This reduction in fasting and stimulated insulin levels is, therefore, due to an increase in the fractional extraction of insulin by the liver rather than to a reduction in pancreatic secretion as had previously been supposed.

annals of clinical biochemistry

The Reduction of Peripheral Insulin Concentrations in Obese Subjects following a Hypocaloric Diet: Reduced Pancreatic Secretion or Increased Hepatic Extraction?