Isotopic studies of carbohydrate metabolism in non-insulin-dependent diabetes mellitus

Isotopic techniques are required for answering many fundamental pathophysiologic questions in diabetes research. Several isolopic methods and results are critically evaluated here, along with a description of recent methodologic advances. Included is the role of hepatic glucose production (HGP) in fasting hyperglycemia, the metabolic source of HGP (gluconeogenesis vs glycogenolysis), whether HGP is substrate-driven, and the tissue location and metabolic fate of glucose disposal. Progress in the measurement of HGP, gluconeogenesis, hepatic substrate fluxes, and hepatic uridine diphosphate-glucose metabolism is described. The uses of isotope-kinetic methods in identifying sites of drug action and genes contributing to non-insulin-dependent diabetes mellitus are also noted.