EFFECTS OF FASTING ON HEPATIC AND PERIPHERAL GLUCOSE-METABOLISM IN CONSCIOUS RATS WITH NEAR-TOTAL FAT DEPLETION

Experimental diabetes and fasting are both associated with hypoinsulin aemia and share several other metabolic features. We investigated hepa tic and peripheral glucose metabolism in young rats after near-total d epletion of their fat mass. Conscious rats were fasted for 72 h (n = 1 3), while 6 h-fasted animals (n = 14) served as controls. Rats were st udied either during saline infusion or insulin (18 m-units/kg per min) -clamp studies. In fasting, despite a 2-fold increase in hepatic gluco se-6-phosphatase (Glc-6-Pase) V-max. (from 16 +/- 2 mu mol/g of liver per min in control; P<0.001), the basal hepatic glucose production (HG P) decreased by 47% [from 88 +/- 3 mu mol/kg lean body mass (LBM) per min in control; P < 0.01]. The decreased HGP in fasting was associated with a 70% decrease in the hepatic levels of glucose 6-phosphate (Glc -6-P) (from 366 +/- 53 nmol/g wet wt. in control; P < 0.01). Thus Glc- 6-Pase activity assayed in the presence of the Glc-6-P levels found in vivo was decreased by 44%. During hyperinsulinaemia, peripheral gluco se uptake was decreased by 15% with 3 days of fasting (from 272 +/- 17 mu mol/kg LBM per min in control; P < 0.01). This was completely acco unted for by a 42% decrease in whole-body glycolysis (P < 0.01), while the rate of glycogen synthesis was unchanged. Thus fasting (after nea r-total fat depletion) differs from experimental diabetes because: (1) despite markedly increased Glc-6-Pase, HGP is decreased in fasting, d ue to a marked decrease in the substrate level (Glc-6-P) in vivo; and (2) the impairment in peripheral insulin sensitivity in fasting is due to a decrease in the glycolytic, and not the glycogen-synthetic, path way.