This project will evaluate changes in carbohydrate metabolism that occur during postoperative liver regeneration following partial hepatectomy and the result of selective immunoneutralization of gastrointestinal hormones on regeneration. An increasing number of clinical major partial hepatectomies (50% and greater resection) are being performed. Postoperatively, there appears to be glucose homeostasis with minimal supplementation. Since the liver is the major source of newly synthesized glucose in the body, there must be significant changes in the handling of insulin and glucose, and the interactions and effects that insulin has on the liver's ability to produce new glucose. Additionally, investigations have shown that one of the major hepatotrophic factors, epidermal growth factor (EGF), may have insulin-like actions and may affect glucose homeostasis in the regenerating liver. An in depth investigation into the alterations in carbohydrate metabolism that occur following partial hepatectomy is appropriate. Dogs and rats following 60-70% hepatectomy will be studied. The canine studies will complete preliminary work already begun in this area. Rats will undergo preoperative and postoperative oral glucose tolerance tests and tritiated euglycemic glucose clamps to assess: (1) their ability to handle a glucose load, (2) the ability to secrete insulin in response to such load, (3) basal hepatic glucose production, (4) the ability of insulin to suppress steady state hepatic glucose production, (5) total body glucose disposal in response to sustained hyperinsulinemia, peripheral sensitivity to insulin, and (6) the effect of EGF on insulin- liver glucose production interactions. These tests will be performed at sequential, well defined intervals postoperatively so that calculations of hepatic glucose production can be adjusted to compensate for the remaining liver mass at various stages of regeneration. Rat studies using selective immunoneutralization of insulin, EGF, and somatostatin will be performed using antisera to these hormones. Using postoperative physiologic studies and serial sacrifice we will ascertain the result of the selective absence of these hormones on liver regeneration. The dogs will undergo the oral glucose tolerance tests, tritiated euglycemic glucose clamps, and pre and postoperative liver scans to determine residual liver mass. These investigations are directed toward achieving optimal postoperative management of patients undergoing major liver resection and toward improving the understanding of the physiology involved in postoperative glucose homeostasis.
| Kogut, K A; Nifong, L W; Witt, M J et al. (1998) Hepatic insulin extraction after major hepatectomy. Surgery 123:415-20 |
| Jones, C E; Koshibu, K; DeCambre, M et al. (1998) The Kidney's role in glucose balance following partial hepatectomy. J Surg Res 79:136-40 |
