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Chronic free fatty acid infusion in rats results in insulin resistance but no alteration in insulin-responsive glucose transporter levels in skeletal muscle

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Lipids

Abstract

To investigate the mechanism by which free fatty acids (FFA) affect glucose uptake, we studied the effect of chronic elevation (24 h) of plasma FFA in rats on whole body glucose disposal and glucose utilization index (GUI) in the basal state and under a euglycemic hyperinsulinemic clamp in relation to the amount of insulin-responsive glucose transporter (IRGT, i.e., GLUTU), protein in different muscles (oxidative and glycolytic) and adipose tissue. Infusion of Intralipid in the basal state led to a∼40% increase in whole body glucose uptake and a∼250% increase in GUI in adipose tissue as compared to control rats. There was no change in the amount of IRGT protein in any of the muscle types whereas in fat depots it was either unchanged or decreased. Under moderate or supraphysiological hyperinsulinemia, increment of whole body glucose disposal was significantly lower in Intralipid perfused rats when compared to controls (∼110 μU/mL: 0.7±0.1 vs. 1.3±0.1 mg/min,P<0.02; ∼1000 μU/mL: 3.0±0.2 vs. 3.9±0.4 mg/min,P<0.02). Under moderate hyperinsulinemia stimulation, GUI was significantly reduced in different muscles and adipose tissue as compared to controls. We conclude that peripheral insulin resistance which occurs after elevation of plasma FFA levels does not seem to be explained by changes in the amount of IRGT protein in either oxidative or glycolytic skeletal muscle. Thus fatty acid infusion appears to be associated with a defect in IRGT translocation to the plasma membrane, fusion with the membrane, or intrinsic activity.

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Abbreviations

FFA:

free fatty acids

GUI:

glucose utilization index

IRGT:

insulin-sensitive glucose transporter

Ra:

rate of glucose appearance

Rd:

rate of glucose disappearance

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Authors and Affiliations

  1. Laboratoire de Physiopathologie de la Nutrition, CNRS U 307, Université Paris 7, Case 7126, 75251, Paris Cedex 05, France

    C. Magnan & M. Gilbert

  2. Harvard Thorndike Laboratory of Beth Israël Hospital, Harvard Medical School, 02215, Boston, Massachusetts

    B. B. Kahn

Authors
  1. C. Magnan
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  2. M. Gilbert
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  3. B. B. Kahn
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Magnan, C., Gilbert, M. & Kahn, B.B. Chronic free fatty acid infusion in rats results in insulin resistance but no alteration in insulin-responsive glucose transporter levels in skeletal muscle. Lipids 31, 1141–1149 (1996). https://doi.org/10.1007/BF02524288

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  • DOI: https://doi.org/10.1007/BF02524288

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