Insulin Secretion and Cellular Glucose Metabolism after Prolonged Low-Grade Intralipid Infusion in Young Men

• Published in: The journal of clinical endocrinology and metabolism 2003-06, Vol.88 (6), p.2775-2783
• Main Authors: Jensen, Christine B., Storgaard, Heidi, Holst, Jens J., Dela, Flemming, Madsbad, Sten, Vaag, Allan A.
• Format: Article
• Language: English
• Subjects: Adult; Area Under Curve; Biological and medical sciences; Blood Glucose - metabolism; C-Peptide - blood; Carbohydrates; Endocrine pancreas; Fat Emulsions, Intravenous - pharmacology; Fatty Acids, Nonesterified - blood; Fundamental and applied biological sciences. Psychology; Glucagon - blood; Glucose - metabolism; Glucose Tolerance Test; Hormones. Régulation; Humans; Insulin - blood; Insulin - metabolism; Insulin Resistance; Insulin Secretion; Male; Metabolisms and neurohumoral controls; Oxidation-Reduction; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2002-021430

We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m2·min; high insulin clamp (HI), 40 mU/m2·min], 3-3H-glucose, indirect calorimetry, and iv glucose tolerance test. Free fatty acid concentrations were similar during basal steady state but 3.7- to 13-fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio decreased at both LI and HI during Intralipid infusion. At LI, glucose oxidation decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and glucose production were not significantly altered. At HI, glucose disposal, and glucose oxidation decreased by 12% and 24%, respectively, during Intralipid infusion. Glycolytic flux, glucose storage, and glucose production were unchanged. Insulin secretion rates increased in response to Intralipid infusion, but disposition indices (DI = insulin action·insulin secretion) were unchanged. In conclusion, a 24-h low-grade Intralipid infusion caused insulin resistance in the oxidative (but not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes.