Orthotopic pancreas transplantation with portal venous drainage in rats. Surgical technique and metabolic effects(*).

Heterotopic pancreas transplantation in type I diabetic patients does not correct hyperglucagonemia, which is thought to be due to insufficiently suppressed glucagon release by the host pancreas. The diabetogenic effects of glucagon then have to be corrected by higher than normal insulin secretion from the transplant, with the attendant risk of earlier loss of islet cell function, and development of atherosclerosis. To establish whether this situation can be prevented, we investigated glucose homeostasis and blood lipids, as well as fecal fat and chymotrypsin as indicators for pancreatic exocrine function 14 weeks after orthotopic pancreas transplantation in inbred rats. The pancreas was resected before orthotopic transplantation of the donor pancreas with portal venous drainage (n=8). Laparotomized animals served as controls (n=8). Basal plasma glucagon, basal plasma insulin to glucagon molar ratio, and basal and integrated incremental responses of plasma glucose, insulin, and C-peptide after an oral glucose load (2 g/kg body weight) were similar in both groups. However, hepatic insulin clearance was slightly but significantly lower in the transplanted group (1.1+/- 0.1 vs 1.6+/-0.2; P<0.05). Basal plasma levels of free fatty acids, phospholipids, triglycerides, cholesterol, low-density lipoproteins, and high-density lipoproteins were unchanged after transplantation. Also unchanged were fecal fat and chymotrypsin levels, thus indicating preserved pancreatic exocrine function. We concluded that orthotopic pancreas transplantation with portal venous drainage achieves almost optimal metabolic control with respect to endocrine and exocrine pancreatic function as well as blood lipids. This technique could therefore be used to treat combined endocrine and exocrine insufficiency in chronic pancreatitis and thus enlarges the spectrum of indications for pancreas transplantation.