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Insulin sensitivity and glucose tolerance following transposition of pancreatic venous drainage to the systemic circulation.

In these studies it has been demonstrated that the diversion of pancreatic venous drainage to the systemic circulation (1) increases the peripheral insulinemia and metabolic clearance of glucose under basal conditions; (2) decreases insulin sensitivity, as measured by the hyperinsulinemic euglycemic clamp, more than 2-fold; and (3) decreases peripheral insulin sensitivity and the suppression of endogenous glucose production during exogenous glucose infusion. In spite of these changes, tolerance to the intravenously infused glucose improves. This is accounted for by higher insulin concentrations following diversion, more than compensating for decreases in insulin sensitivity and the suppression of endogenous glucose production. Data on insulin sensitivity and glucose tolerance after pancreas transplantation are not completely consistent, as discussed above. When the site of venous drainage of the pancreas was the only factor altered in the experimental model, unequivocal insulin resistance resulted. This occurred in a relatively short period (ie, 2 weeks). The results here are consistent with a number of studies that have demonstrated normal glucose tolerance coupled with hyperinsulinemia in a partially pancreatectomized dog model as well as in human pancreas transplants. Data presented here imply that the hyperinsulinemia which results after surgical diversion of the pancreatic venous drainage from the portal to the systemic circulation causes an important degree of insulin resistance. Physiological insulin delivery and therefore portal drainage during transplantation may therefore be relevant for the complete normalization of glucoregulation in diabetes. The reduction of hyperinsulinemia may also be important in light of the recent emphasis on the role that this and insulin resistance may play in the development of complications such as cardiovascular disease or hypertension.