Platelet-activating factor-induced increases in glucose kinetics

Abstract

Platelet-activating factor (PAF) is a postulated mediator of many of the early hemodynamic effects of endotoxin. The aim of the present study was to determine whether in vivo administration of PAF could produce alterations in whole-body glucose metabolism that would mimic those seen during endotoxemia. Glucose kinetics were assessed in chronically catheterized conscious rats by the constant infusion of [6-3H]- and [U-14C]glucose before and for 4 h after either a bolus injection (300 ng/kg) or a constant infusion (20 or 220 ng.min-1.kg-1) of PAF. The bolus injection of PAF produced a 30% decrease in blood pressure by 5 min that returned to control levels by 30 min. Increased plasma glucose (40%) and lactate (150%) levels after injection of PAF were also transient. In contrast, the bolus injection of PAF elevated the rate of glucose appearance (Ra; 44%) for 1.5 h. The lower PAF infusion rate decreased blood pressure 11% to 104 mmHg, whereas the higher infusion rate decreased pressure 34% to 77 mmHg. Both PAF infusion rates produced elevations in plasma glucose (28, 150%) and glucose Ra (20, 60%) throughout the 4-h infusion period in a dose-related manner. The PAF infusions also induced dose-related increases in plasma glucagon and catecholamine levels throughout the infusion period. In a separate group of experiments a complete adrenergic blockade, produced by the constant infusion of propranolol and phentolamine, completely prevented PAF-induced increases in glucose kinetics and the hyperglucagonemia.(ABSTRACT TRUNCATED AT 250 WORDS)