Effect of hyperglycemia-hyperinsulinemia on whole body and regional fatty acid metabolism

The effects of combined hyperglycemia-hyperinsulinemia on whole body, splan chnic, and leg fatty acid metabolism were determined in five volunteers. Ca theters were placed in a femoral artery and vein and a hepatic vein. U-C-13 -labeled fatty acids were infused, once in the basal state and, on a differ ent occasion, during infusion of dextrose (clamp; arterial glucose 8.8 +/- 0.5 mmol/l). Lipids and heparin were infused together with the dextrose to maintain plasma fatty acid concentrations at basal levels. Fatty acid avail ability in plasma and fatty acid uptake across the splanchnic region and th e leg were similar during the basal and clamp experiments. Dextrose infusio n decreased fatty acid oxidation by 51.8% (whole body), 47.4% (splanchnic), and 64.3% (leg). Similarly, the percent fatty acid uptake oxidized decreas ed at the whole body level (53 to 29%), across the splanchnic region (30 to 13%), and in the leg (48 to 22%) during the clamp. We conclude that, in he althy men, combined hyperglycemia-hyperinsulinemia inhibits fatty acid oxid ation to a similar extent at the whole body level, across the leg, and acro ss the splanchnic region, even when fatty acid availability is constant.