HYPERINSULINEMIA INHIBITS HEPATIC PEROXISOMAL BETA-OXIDATION IN RATS

Studies show that insulin deficiency enhances peroxisomal enzyme activ ities. It is not known, however, whether hyperinsulinemia exerts the o pposite effect on peroxisomes. Male Sprague-Dawley rats were infused w ith normal saline, glucose or galactose for 7 days. Only glucose cause d an increase in serum insulin levels. The increase in insulin secreti on, in response to glucose, was blocked with diazoxide. Data show an i nverse relationship between serum insulin levels and hepatic peroxisom al beta-oxidation (r(2) = 0.90, p < 0.01). While hyperinsulinemic rats had diminished peroxisomal beta-oxidation, lowering serum insulin res tored peroxisomal enzyme activity to normal levels. These effects were independent of blood glucose levels (r(2) = 0.35). In addition to dec reasing peroxisomal beta-oxidation, hyperinsulinemia was accompanied b y accelerated animal mortality, an effect which was also prevented by lowering serum insulin levels. Peroxisomal deficit may be a potentiall y lethal consequence of hyperinsulinemia.