Effects of free fatty acids and glucose on splanchnic insulin dynamics

Diabetes
M M HennesA H Kissebah

Abstract

The mechanism of hyperinsulinemia that accompanies insulin resistance in some abdominally obese and diabetic individuals is poorly understood. Both increased secretion of insulin and decreased clearance have been demonstrated. The present study was undertaken to examine the role of free fatty acids (FFAs) and glucose in regulating splanchnic insulin dynamics in vivo. Plasma FFA levels were raised approximately twofold via an intralipid/heparin infusion in eight lean women. Insulin dynamics were assessed using the individual's C-peptide kinetic coefficients. Studies were performed in the basal state and during two levels of glycemia, 7 and 11 mmol/l. Studies were repeated using saline, and thus each subject served as her own control. Under basal conditions, raising FFA flux resulted in a modest increase in plasma insulin concentration (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 resulted in a 30% increase in PIC above the effect produced by glucose alone. This represents the cumulative effects of stimulation of ISR and inhibition of EIC. Clamping plasma glucose at 11 mmol/l while...Continue Reading

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