Regional substrate metabolism during prolonged hyperglycemia in humans

The effect of prolonged (15 hours) hyperglycemia (glucose ∼160 mg/dl) on splanchnic and leg substrate metabolism was investigated. Catheters were inserted in a peripheral vein for tracer infusion and in a femoral artery, femoral vein and a hepatic vein for blood sampling. [U-¹³C] fatty acids (0.03 μmol/kg.min) were infused for 15h. Plasma FFA enrichment and concentration were maintained constant by infusion of lipids and heparin. Splanchnic and leg blood flow was measured by constant infusion of Indocyanin Green. Results: Neither splanchnic nor leg blood flow changed significantly during the clamp. Splanchnic Bed: Net glucose balance switched from net release during basal (9±1 mg/dl) to net uptake during the clamp (36±12 mg/dl, p<0.05). Fatty acid uptake by the splanchnic bed did not change with hyperglycemia. However, fatty acid oxidation decreased by 57.7% (p<0.05) during the clamp. Leg: Glucose uptake by the leg increased from 1.4±0.8 mg/dl during basal to 24±13 mg/dl during the clamp (p<0.05). Fatty acid uptake decreased from 0.62±0.18 to 0.45±0.16 μmol/kg.min during the clamp (p<0.05), whereas fatty acid oxidation dropped by 63% (p<0.05)). Conclusion: Prolonged hyperglycemia increases glucose but attenuates fatty acid oxidation across both the splanchnic region and the leg in human volunteers. The decrease in splanchnic fatty acid oxidation during the clamp was not accompanied by a drop in FFA uptake, suggesting channeling of FFA into triacylglycerols. This could explain the increased triacylglycerol concentration observed in high carbohydrate feeding.