The effect of systemic venous drainage of the pancreas on insulin sensitivity in dogs.

Abstract

To assess the metabolic consequences of the diversion of the pancreatic venous drainage to the systemic circulation, the pancreaticoduodenal and gastrosplenic veins were anastomosed to the inferior vena cava in nine normal dogs. This procedure maintained the integrity of the entire pancreas while shunting the hormonal output ofthe pancreas to the periphery. The metabolic effects were assessed from the sensitivity to insulin during a euglycemic hyperinsulinemic glucose clamp using an insulin infusion of 800 IAU/kg per min. The studies were controlled by their duplication in seven dogs identically treated but with the pancreatic veins reanastomosed to the portal vein. No differences in systemic insulin levels or insulin sensitivity before and after surgery were seen under these circumstances. After diversion, however, basal insulin levels rose from 4.5±1.0 to 11.5±2.5 gU/ml. Basal glucose metabolic clearance rate (MCR) rose to 3.0±0.4 from 2.0±0.3 ml/kg per min. On insulin infusion, maximal stimulation of MCR within the 2-h infusion period was to 15.2±2.5 ml/kg per min preoperatively and to 7.2±0.8 ml/kg per min after diversion. Using ratios of MCR-to-insulin concentration as an index of insulin sensitivity, it was demonstrated that this index decreased by at least 50% after diversion. These data imply that portal venous drainage of the pancreas is an important factor in the determination of peripheral insulin sensitivity. (J. Clin. Invest. 92:1713-1721

The effect of portal and peripheral insulin delivery on carbohydrate and lipid metabolism in a miniature pig model of human IDDM

“…Isoglycaemic hyperinsulinaemic clamp data in normal and diabetic pigs after 4 weeks of peripheral and hepatic insulin delivery can remove between 50 and 75 % of insulin in the fasting state [55]. A lack of agreement exists among previous animal investigations, performed in rodents or dogs, concerning whether or not insulin delivery by the peripheral route results, as in our study, in raised [3,7,9,13,[17][18][19][20][21] or unchanged [2,6,11,[14][15][16] peripheral insulin levels. Studies in man comparing intraperitoneal and subcutaneous insulin delivery have similarly yielded conflicting results relating to the extent of systemic insulinisation [23][24][25][26][27][28]56].…”

“…Indeed some acute experiments have shown that peripherally delivered insulin is more effective than the same dose delivered portally [1,5]. A number of investigations have supported the concept that only portal insulin delivery can sustain normal insulin responsiveness [13,18,20]. Others, however, have yielded contradictory findings [2,4,7,11,14,17,19].…”

“…In some studies control of hepatic glucose output or blood glucose concentrations was superior with the portal route of insulin delivery, [3,8,15,16,18,20] while in others no Diabetologia (1997Diabetologia ( ) 40: 1125Diabetologia ( -1134 The effect of portal and peripheral insulin delivery on carbohydrate and lipid metabolism in a miniature pig model of human IDDM Summary A pig model of insulin-dependent diabetes was used to examine the importance of the portal-systemic insulin gradient for whole-body metabolic control. Six pigs had jugular vein, portal vein, and carotid artery cannulae implanted before being made diabetic (150 mg kg − 1 streptozotocin).…”

Insulin signaling is required for insulin’s direct and indirect action on hepatic glucose production

“…We speculated that the marked chronic hyperinsulinemia in the LIRKO mice might have led to secondary insulin resistance in muscle and fat (20)(21)(22) and perhaps limited insulin action on these extrahepatic tissues. We therefore treated a second group of LIRKO mice with streptozotocin (LIRKO+STZ mice) to reduce hyperinsulinemia in an We and others have suggested that insulin predominantly acts indirectly to inhibit hepatic glucose production (HGP) via suppression of gluconeogenic precursors, FFAs, and glucagon.…”

Transplantation in Diabetics with End-Stage Renal Disease

“…Portal drainage is a more physiological alternative, but with regards to the complication rate; graft and patient survival there are not any significant differences. Some data suggests that portal venous drainage is an important factor to determine peripheral insulin sensitivity (Radziuk et al, 1993). In portal venous drainage, serum glucose and insulin concentration recover to normal in contrast with systemic venous drainage, where plasma insulin levels are increased, as a result of bypassing liver circulation (Gu et al, 2002).…”