Abstract

The metabolic actions of caffeine were investigated in the rat (90 mg/kg bw caffeine intravenously during 3 hours) and in human volunteers (35 mg/kg bw caffeine orally) in the fasting state. Additionally, the effects of caffeine were measured during simultaneous intravenous glucose infusion (0.25 mg/kg bw/h during 6 hours in humans and 1.8 mg/kg bw/h during 3 hours in the rat). In the fasting rat, intravenous caffeine caused an increase in the serum concentrations of glucose, urea, insulin, and free fatty acids, whereas a decrease in glucoplastic amino acids was found. As the liver glycogen concentration was not altered, the increase in blood glucose should be due to an increase in glyconeogenesis. During simultaneous application of carbohydrates and caffeine, the increases in the concentration of blood glucose and serum insulin were intensified, whereas the serum concentrations of lactate and urea as well as hepatic glycogen were not altered. In fasting male volunteers caffeine caused an increase in the concentrations of blood glucose, cortisol, insulin, free fatty acids, free glycerol and ketone bodies. During intravenous glucose infusion, caffeine intensified the decrease in serum phosphate induced by carbohydrates. Neither in volunteers nor in the experimental animal, an alteration in the concentrations of cholesterol or serum triglycerides or serum uric acid was effected by caffeine. It is concluded that high dosed caffeine causes peripheral insulin resistance in the human being as well as in the experimental animal. This peripheral insulin resistance is shown by the simultaneous large increases in concentrations of serum insulin, blood glucose and concentration of free fatty acids. In this situation insulin obviously is not able to inhibit lipolysis or gluconeogenesis nor to increase peripheral glucose utilisation. These metabolic effects of caffeine show some similarities to the metabolic situation in diabetes mellitus type 2 (Non Insulin Dependent Diabetes mellitus).

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