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

Department of Endocrinology and Clinical Research Unit (C.B.J., H.S., S.M., A.A.V.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Steno Diabetes Center (H.S., A.A.V.), 2820 Gentofte, Denmark; Department of Medical Physiology (J.J.H., F.D.), Panum Institute, 2200 Copenhagen N, Denmark; and Copenhagen Muscle Research Centre (F.D.), Rigshospitalet, DK-2100 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Christine B. Jensen, Joslin Diabetes Center, Cellular and Molecular Physiology, One Joslin Place, Boston, Massachusetts 02215. E-mail: cbjensen{at}dadlnet.dk or christine.jensen{at}joslin.harvard.edu.

Abstract

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.

Footnotes

This work was supported by grants from The Danish Diabetes Association, Novo Nordisk Research Foundation, H:S Research Foundation, and The Research Fund for Copenhagen, Greenland and The Faeroe Islands. C.B.J. was granted a research fellow scholarship from The Faculty of Medicine, University of Copenhagen, Denmark.

Abbreviations: AUC, Area(s) under the curve; EGP, endogenous glucose production; EGS, exogenous glucose storage; FFA, free fatty acid; FFM, fat free mass; GF, glycolytic flux; GOX, glucose oxidation; HI, high insulin clamp; ISR, insulin secretion rate(s); IVGTT, iv glucose tolerance test; LI, low insulin clamp; LIPOX, lipid oxidation; NIDDM, non-insulin-dependent diabetes mellitus; NS, not significant.

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