EFFECTS OF FAT ON GLUCOSE-UPTAKE AND UTILIZATION IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES

It was the aim of this study to determine whether FFA inhibit insulin-stimulated whole body glucose uptake and utilization in patients with non-insulin-dependent diabetes. We performed five types of isoglycemic (similar to 11 mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin; (c) with insulin plus glycerol; (d) with saline; (e) with saline plus fat/heparin and two types of euglycemic (similar to 5 mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin, During these studies, we determined rates of glucose uptake, glycolysis (both with 3[H-3]glucose), glycogen synthesis (determined as glucose uptake minus glycolysis), carbohydrate oxidation (by indirect calorimetry) and nonoxidative glycolysis (determined as glycolysis minus carbohydrate oxidation), Fat/heparin infusion did not affect basal glucose uptake, but inhibited total stimulated (insulin stimulated plus basal) glucose uptake by 40-50% in isoglycemic and in euglycemic patients at plasma PFA concentration of similar to 950 and similar to 550 mu M, respectively, In isoglycemic patients, the 40-50% inhibition of total stimulated glucose uptake was due to near complete inhibition of the insulin-stimulated part of glucose uptake, Proportional inhibition of glucose uptake, glycogen synthesis, and glycolysis suggested a major FFA-mediated defect involving glucose transport and/or phosphorylation, In summary, fat produced proportional inhibitions of insulin-stimulated glucose uptake and of intracellular glucose utilization, We conclude, that physiologically elevated levels of FFA could potentially be responsible for a large part of the peripheral insulin resistance in patients with non-insulin-dependent diabetes mellitus.