Effects of a 48-h Fat Infusion on Insulin Secretion and Glucose Utilization

Abstract

To determine the effects of prolonged elevation of plasma free fatty acids (FFAs) on insulin secretion, we infused Liposyn II (4.3 μmol · kg−1 · min−1) plus heparin (0.4 U · kg−1 · min−1) intravenously into six healthy volunteers for 48 h. Another six volunteers received saline infusions and served as control subjects. In all 12 subjects (11 men and 1 woman), plasma glucose was clamped at ∼8.6 mmol/l. Liposyn/heparin infusion resulted in a 9.4-fold increase in plasma FFA concentration (from 132 to 1,237 μmol/l), a 46% increase in insulin secretion rates (from 241 to 352 pmol/min, P < 0.05) (determined by deconvolution of plasma C-peptide concentration), and a 30% decrease, during the initial 24 h, in the rate of glucose infusion needed to maintain hyperglycemia (from 55.5 to 39.1 μmol · kg−1 · min−1, P < 0.02). This decrease disappeared during the second 24 h. In summary, we found that physiologically elevated plasma FFAs 1) potentiated glucose-stimulated insulin secretion for 48 h and 2) initially caused peripheral insulin resistance that disappeared during the 2nd day, probably as a result of elevated circulating insulin levels. We conclude that in healthy volunteers under hyperglycemic conditions, fat infusion produced insulin resistance that was compensated for after ∼24 h by persistent hypersecretion of insulin.