Comparison of subcutaneous and intraportal insulin administrations on adenylate energy charge of the liver in diabetic rats.
Effects of subcutaneous 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. The diabetic rats were classified into two 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 both groups were not significantly different from those of controls. In the first group, the oxidative phosphorylation of liver mitochondria was within normal limits and was enhanced significantly by subcutaneous administration 4 U. of insulin (p less than 0.005). In the secong group, the mitochondrial oxidative and phosphorylative activities were inhibited severely and did not recover even with subcutaneous administration of 20 U. of insulin. Intraportal administration of insulin doses (4 to 8 U.) insufficient for normalization of hyperglycemia produced a decrease in the energy charge of the liver to a considerably lower level than normal (p less than 0.01), whereas larger doses (20 U.) of insulin raised the energy charge to normal levels, with a concomitant recovery of mitochondrial oxidative phosphorylation. It is suggested that subcutaneous administration of insulin is effective for hepatic energy metabolism only if insulin response to glucose loading is still present but that only intraportal administration of insulin can exert a beneficial effect in diabetic rats without insulin response.
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D010085:Oxidative Phosphorylation; D011169:Portal Vein; D051381:Rats
D000227:Adenine Nucleotides; D007328:Insulin; D005947:Glucose