EFFECTS OF FREE FATTY-ACIDS AND GLUCOSE ON SPLANCHNIC INSULIN DYNAMICS

The mechanism of hyperinsulinemia that accompanies insulin resistance in some abdominally obese and diabetic individuals is poorly understoo d. Both increased secretion of insulin and decreased clearance have be en demonstrated. The present study was undertaken to examine the role of free fatty acids (FFAs) and glucose in regulating splanchnic insuli n dynamics in vivo. Plasma FFA levels were raised approximately twofol d via an intralipid/heparin infusion in eight lean women. Insulin dyna mics were assessed using the individual's C-peptide kinetic coefficien ts. Studies were performed in the basal state and during two levels of glycemia, 7 and 11 mmol/l. Studies were repeated using saline, and th us each subject served as her own control. Under basal conditions, rai sing FFA flux resulted in a modest increase in plasma insulin concentr ation (PIC) secondary to an increase in insulin secretion rate (ISR); however, endogenous insulin clearance (EIC) was not influenced. During the 7 mmol/l hyperglycemic clamp, maintaining a high FFA flux resulte d in a 30% increase in PIC above the effect produced by glucose alone. This represents the cumulative effects of stimulation of ISR and inhi bition of EIC. Clamping plasma glucose at 11 mmol/l while maintaining a high FFA flux increased PIC twofold above that produced by glucose a lone. This increase in PIC was mainly due to a significant reduction i n EIC without an accompanying increase in ISR (392 +/- 159 and 787 +/- 187 ml/min with and without intralipid infusion, respectively). Analy sis of variance indicated that the suppressive effect of FFA on EIC wa s independent of the effect of glucose. The effect of the two substrat es seems to be additive.