AJP - Endocrinology and Metabolism, Vol 270, Issue 3 E424-E429, Copyright © 1996 by American Physiological Society
Differential effects of acute hypertriglyceridemia on insulin action and insulin receptor autophosphorylation
B. Gumbiner, J. F. Mucha, J. E. Lindstrom, I. Rekhi and J. N. Livingston
Department of Medicine, University of Rochester School of Medicine and Dentistry, New York 14620, USA.
Experimentally induced hypertriglyceridemia (HTG) and high plasma free
fatty acid (FFA) levels impair in vivo insulin action. To determine if this
is a consequence of impaired in vivo insulin receptor autophosphorylation
and related to defective receptor signaling, hyperinsulinemic euglycemic
clamps, indirect calorimetry, and skeletal muscle biopsies were performed
in nine healthy subjects. In vivo insulin action was determined from the
glucose infusion rate (GINF) and glucose oxidation (Glcox) during 40 and
120 mU/m2 /min clamps with (HTG clamp) and without (control clamp) a
triglyceride emulsion infusion. The percentage of receptors
autophosphorylated in vivo was determined by 125I-labeled insulin tracer
binding in skeletal muscle immunoprecipitates of insulin receptors and
phosphorylated receptors. Compared with the control clamps, plasma
triglycerides and FFA increased four- and twofold, whereas GINF and Glcox
decreased 15 and 35%, respectively, during the HTG clamps (all P<0.05).
However, the percentages of receptors phosphorylated after the 40 and 120
mU/m2/min HTG clamps (9.2 +/- 1.5 and 21.1 +/- 2.6%, respectively) were
similar to the control clamps (9.0 +/- 0.6 and 18.6 +/- 2.2%,
respectively). These results indicate that, if impaired insulin signal
transduction is a mechanism by which HTG and FFA impair insulin action, it
occurs at a site downstream from insulin receptor autophosphorylation.
