Lack of a gastrointestinal mediator of insulin action in maturity-onset diabetes.

It is suggested that hepatic uptake of orally ingested glucose depends not only on insulin secretion but also on the release of a gastrointestinal factor which mediates insulin action on the liver. In maturity-onset diabetes characterised by hyperinsulinaemia and insulin resistance, deficiency of this gastrointestinal factor may be the primary pathogenetic event leading to postprandial hyperglycaemia. Postprandial hyperglycaemia brings about an increase in insulin secretion; and hyperinsulinaemia, in turn, results in decreased binding of insulin to its receptor and in peripheral (extrahepatic) resistance to insulin.