Studies on the mechanism of activation of adipose tissue pyruvate dehydrogenase by insulin.

Incubation of rat epididymal adipose tissue fragments with insulin led to increases of up to 2.4-fold in the activity of pyruvate dehydrogenase subsequently assayed in tissue homogenates. The activation of pyruvate dehydrogenase by insulin was greatest when tissue was incubated in the presence of bicarbonate ions and when 2 mg of glucose or fructose per ml was added to the incubation medium. Several other agents known to inhibit lipolysis and to decrease cyclic AMP levels in fat cells, including niacin, 5-methylpyrazole-3-carboxylic acid, and prostaglandin El were also effective in activating pyruvate dehydrogenase. Severe depletion of tissue ATP levels caused by the addition of oligomycin or dinitrophenol, by anaerobic incubation, or by prolonged incubation with epinephrine in the absence of albumin also activated pyruvate dehydrogenase. Incubation of adipose tissue with 1 rnM oleate, 1.5 mM octanoate, 1.5 rnx heptanoate, 1 mM butyrate, or 3 lflM DL-P-hydroxybutyrate decreased pyruvate dehydrogenase activity 20 to 70%. The addition of 5 my acetate, 5 mM propionate, or 3 rnM 4-pentenoate led to 70 to 160% activation of pyruvate dehydrogenase, whereas 1.5 mM pentanoate had no effect. High concentrations of glucose (20 mg per ml) or of pyruvate-lactate (5 and 30 mM, respectively) also increased tissue pyruvate dehydrogenase activity.