Normalization of six key hepatic enzymes after fetal pancreas transplantation in diabetic rats.
In diabetic rats transplanted with fetal pancreata we measured the activities of six important enzymes to assess the return of liver metabolism to normal. Comparison was made among the responses of transplanted rats with and without renal-portal vein shunts and of those not transplanted and injected with insulin in varying doses. Insulin supply was not limited since three or four fetal pancreata were first grown in normal rats before transfer into the diabetic animals. Transplantation normalized blood and urine glucose and the rate of disappearance of intravenous glucose. Glucokinase and pyruvate kinase activities in liver rose toward normal at 7 days after transplantation and reached normal levels at 30 and 90 days. The response of the other four enzymes, glucose-6-phosphate dehydrogenase, citric lyase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase, was more rapidly restored to normal at 7 days and remained normal at 30 and 90 days. No difference was observed in the enzyme activities of transplanted-shunted rats to nonshunted animals. Glucokinase activity was restored to normal after 1 wk of daily injections of 1 U of PZI; pyruvate kinase restoration required 3 U/day. Glucose-6-phosphate dehydrogenase and citric lyase required 2 U/day to be restored to normal; 3 U daily resulted in temporary supernormal activities. The gluconeogenic enzymes, fructose-1,6-bisphosphatase and glucose-6-phosphatase, were only partially suppressed toward normal by insulin even with 3 U daily for 3 wk. These findings indicate that pancreas transplantation is a more effective regulator of liver metabolism in diabetes than insulin injections.
D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005941:Glucokinase / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology*; D008297:Male; D010179:Pancreas / Q000196:embryology; D016035:Pancreas Transplantation; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D007328:Insulin; D005954:Glucosephosphate Dehydrogenase; D001275:ATP Citrate (pro-S)-Lyase; D005941:Glucokinase; D011770:Pyruvate Kinase; D006597:Fructose-Bisphosphatase; D005952:Glucose-6-Phosphatase