COMPARISON OF SUBCUTANEOUS AND INTRAPORTAL INSULIN ADMINISTRATIONS ON ADENYLATE ENERGY-CHARGE OF LIVER IN DIABETIC RATS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 89  (5) , 937-945
Abstract
Effects of s.c. and intraportal administrations of insulin on adenine nucleotide metabolism of the liver and oxidative phosphorylation of the isolated mitochondria were investigated in alloxan-diabetic rats. Diabetic rats were classified into 2 groups according to the severity of impaired insulin response to oral glucose: diabetic rats with only minor impairment of insulin response and those with severely defective response. The energy charge levels (ATP + 1/2ADP)/(ATP + ADP + AMP) of the liver in both groups were not significantly different from those of controls. In the 1st group, oxidative phosphorylation of liver mitochondria was within normal limits and was enhanced significantly by s.c. administration of 4 U [units] of insulin (P < 0.005). In the 2nd group, mitochondrial oxidative and phosphorylative activities were inhibited severely and did not recover even with s.c. administration of 20 U of insulin. Intraportal administration of insulin doses (4-8 U) insufficient for normalization of hyperglycemia decreased the energy charge of the liver to a considerably lower than normal (P < 0.01), whereas larger doses (20 U) of insulin raised the energy charge to normal levels, with a concomitant recovery of mitochondrial oxidative phosphorylation. S.C. administration of insulin is effective for hepatic energy metabolism only if insulin response to glucose loading is still present, but only intraportal administration of insulin can exert a beneficial effect in diabetic rats without insulin response.