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 (approximately 11mM) 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 (approximately 5mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin. During these studies, we determined rates of glucose uptake, glycolysis (both with 3[3H] 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 FFA concentration of approximately 950 and approximately 550 microM, 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.
Boden
G
G
Division of Endocrinology/Metabolism, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Chen
X
X
D000368:Aged; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004655:Emulsions; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010743:Phospholipids; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012450:Safflower Oil; D013024:Soybean Oil
D001786:Blood Glucose; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D011994:Recombinant Proteins; C063336:safflower oil, soybean oil, phospholipid emulsion; D007336:Insulin, Isophane; D013024:Soybean Oil; D012450:Safflower Oil; D006493:Heparin; D005934:Glucagon; D005947:Glucose