Chronic Hyperinsulinemia in the Fetal Rhesus Monkey: Effects on Hepatic Enzymes Active in Lipogenesis and Carbohydrate Metabolism

  1. Robert Schwartz
  1. Sections of Reproductive and Developmental Medicine and Pathology, Brown University Program in Medicine; and the Departments of Pediatrics at Rhode Island Hospital and of Pathology and Obstetrics and Gynecology at Women and Infants Hospital Providence, Rhode Island
  1. Address reprint requests to Robert Schwartz, M.D., Department of Pediatrics, Rhode Island Hospital, Providence, Rhode Island 02902.

Abstract

Hyperinsulinemia was produced in fetal rhesus monkeys for 21 days in the last third of gestation by subcutaneous pork insulin injected at 19 U a day. Plasma insulin concentrations in treated fetuses (N = 4) were 3525 μU/ml compared with controls' (N = 6) 51 μ/ml. There was no difference in paired pre- and post-treatment fetal plasma glucose concentration. Activity of the hepatic enzymes that promote glucose utilization (glucokinase and hexokinase) and glycolysis (phos-phofructokinase, pyruvate kinase, and pyruvate dehy-drogenase) was unaffected. Similarly, glycogen metabolism enzymes (active and inactive synthase and phosphorylase) were unaltered. Two gluconeogenic enzymes (PEPCK and glucose-6-phosphatase) were diminished in the treated group compared with controls. Fetal hyperinsulinemia enhanced lipogenic and NADPH-producing enzyme activities, as evidenced by a twofold increase in fatty acid synthase and in citrate cleavage enzyme activity. Malic enzyme was absent. Hyperinsulinemia with euglycemia (1) increases the activity of enzymes that participate in lipogenesis, (2) decreases some of those controlling gluconeogenesis, and (3) has no effect on the enzymes of glycolysis.

  • Received June 14, 1979.
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