This project will evaluate changes in carbohydrate metabolism during liver regeneration. An increasing number of major partial hepatectomies are being performed. Postoperatively, there is glucose homeostasis with minimal supplementation. Because the liver is the major source of newly synthesized glucose, there must be significant changes in the reduced hepatic mass's handling of insulin and glucose and insulin's effects on the liver's ability to produce new glucose. Investigations have shown that a major hepatotrophic factor, epidermal growth factor (EGF), may have insulin-like actions and may affect glucose homeostasis during regeneration. Rats will be studied before and after 70% hepatectomy. Using tritiated euglycemic glucose clamps we will assess: (1) ability to handle a glucose load, (2) basal hepatic glucose production (HGP), (3) ability of insulin to suppress steady state HGP, (4) glucose disposal during hyperinsulinemia, and (5) effects of EGF on insulin-liver glucose production interactions. Tests will be performed at intervals postoperatively so that HGP can be adjusted for the remaining liver mass. Studies using selective immunoneutralization of insulin and EGF will be performed with antisera to these hormones. From the clamps and serial sacrifice we will study the result of the selective absence of these hormones on regeneration. A parallel group will undergo 70% hepatectomy and livers will be used for hepatic membrane vesicle preparation to study insulin receptor number and binding affinity. These investigations should provide an understanding of the physiology involved in postoperative glucose homeostasis, and facilitate optimal postoperative management of patients undergoing major liver resection.
