Effect of lipid oxidation on glucose utilization in humans.
The mechanisms responsible for the competition between glucose and fatty acids as oxidative fuels are not yet completely understood in humans. Maintenance of plasma fatty acid concentrations by means of lipid and heparin infusion during hyperinsulinemic, euglycemic clamps in humans first suppresses glucose oxidation and only later decreases nonoxidative glucose disposal; muscle pyruvate dehydrogenase activity is inhibited when plasma fatty acid concentrations are maintained during hyperinsulinemic, euglycemic clamps. The maintenance of plasma fatty acid concentrations impairs insulin-stimulated muscle glucose uptake only if fatty acid uptake by skeletal muscles is increased. The role of hyperglycemia in glucose-fatty acid competition has recently been emphasized. Fatty acid utilization by muscle is impaired in patients with type 2 diabetes mellitus during fasting hyperglycemia: both lipid oxidation and uptake of plasma fatty acids by skeletal muscle are impaired during postabsorptive conditions. Hyperglycemia indirectly activates pyruvate dehydrogenase, the rate-limiting enzyme for glucose oxidation. The ability of increased glucose availability to stimulate glucose oxidation and reduce lipid oxidation by skeletal muscle can be considered a corollary of the Randle glucose-fatty acid cycle. It can be concluded that within a reasonable range of carbohydrate-to-fat ratios, the addition of fat to a meal does not decrease postprandial carbohydrate oxidation. Furthermore, high-fat meals do not promote fat oxidation leading to fat storage in adipose tissue.
Jéquier
E
E
Institute of Physiology, Faculty of Medicine, University of Lausanne, Switzerland.
D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D004040:Dietary Carbohydrates / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D010084:Oxidation-Reduction
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D005947:Glucose