Stimulation of non-oxidative glucose utilization by L-carnitine in isolated myocytes

J Mol Cell Cardiol. 1995 Nov;27(11):2465-72. doi: 10.1006/jmcc.1995.0234.

Abstract

The effects of L-carnitine on 14CO2 release from [1-14C]pyruvate oxidation (an index of pyruvate dehydrogenase activity, PDH), [2-14C]pyruvate, and [6-14C]glucose oxidation (indices of the acetyl-CoA flux through citric acid cycle), and [U-14C]glucose (an index of both PDH activity and the flux of acetyl-CoA through the citric acid cycle), were studied using isolated rat cardiac myocytes. L-carnitine increased the release of 14CO2 from [1-14C]pyruvate, and decreased that of [2-14C]pyruvate in a time and concentration-dependent manner. At a concentration of 2.5 mM, L-carnitine produced a 50% increase of CO2 release from [1-14C]pyruvate and a 50% decrease from [2-14C]pyruvate oxidation. L-carnitine also increased CO2 release from [1-14C]pyruvate oxidation by 35%, and decreased that of [2-14C]pyruvate oxidation 30%, in isolated rat heart mitochondria. The fatty acid oxidation inhibitor, etomoxir, stimulated the release of CO2 from both [1-14]pyruvate and [2-14C]pyruvate. These results were supported by the effects of L-carnitine on the CO2 release from [6-14C]- and [U-14C]glucose oxidation. L-carnitine (5 mM) decreased the CO2 release from [6-14C]glucose by 37%, while etomoxir (50 microM) increased its release by 24%. L-carnitine had no effect on the oxidation of [U-14C]glucose. L-carnitine increased palmitate oxidation in a time- and concentration-dependent manner in myocytes. Also, it increased the rate of efflux of acetylcarnitine generated from pyruvate in myocytes. These results suggest that L-carnitine stimulates pyruvate dehydrogenase complex activity and enhances non-oxidative glucose metabolism by increasing the mitochondrial acetylcarnitine efflux in the absence of exogenous fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcarnitine / metabolism
  • Animals
  • Carbon Dioxide / metabolism
  • Carnitine / pharmacology*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Epoxy Compounds / pharmacology
  • Glucose / metabolism*
  • Hypoglycemic Agents / pharmacology
  • Male
  • Mitochondria / metabolism
  • Myocardium / metabolism*
  • Myocardium / ultrastructure
  • Oxidation-Reduction
  • Palmitates / metabolism
  • Pyruvate Dehydrogenase Complex / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Epoxy Compounds
  • Hypoglycemic Agents
  • Palmitates
  • Pyruvate Dehydrogenase Complex
  • Carbon Dioxide
  • Acetylcarnitine
  • Glucose
  • etomoxir
  • Carnitine