Controlled crossover study reveals elevated free fatty acids increase plasma insulin via higher secretion and reduced clearance in lean women, suggesting mechanisms for hyperinsulinemia.
Key Points
To examine the roles of elevated free fatty acids and glucose in regulating splanchnic insulin dynamics, specifically insulin secretion and endogenous clearance in vivo.
Assessed splanchnic insulin dynamics in 8 lean women across basal conditions and two hyperglycemic clamp targets (7 and 11 mmol/l).
Infused intralipid and heparin to raise plasma free fatty acid levels approximately twofold, comparing outcomes against saline control infusions in a within-subject design.
Under basal conditions, elevated free fatty acids modestly increased plasma insulin concentration via increased insulin secretion rate without affecting endogenous insulin clearance.
During a 7 mmol/l glucose clamp, elevated free fatty acids caused a 30% increase in plasma insulin concentration above glucose alone via combined stimulation of insulin secretion and inhibition of clearance.
During an 11 mmol/l glucose clamp, high free fatty acids doubled plasma insulin concentration primarily by significantly reducing endogenous insulin clearance (392 ± 159 vs. 787 ± 187 ml/min with and without intralipid, respectively).