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 hyper-insulinæmia and insulin resistance, deficiency of this gastrointestinal factor may be the primary pathogenetic event leading to postprandial hyperglycæmia. Postprandial hyperglycæmia brings about an increase in insulin secretion; and hyperinsulinæmia, in turn, results in decreased binding of insulin to its receptor and in peripheral (extrahepatic) resistance to insulin.