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 of the 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 microU/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 microU/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.
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- Ader M., Bergman R. N. Peripheral effects of insulin dominate suppression of fasting hepatic glucose production. Am J Physiol. 1990 Jun;258(6 Pt 1):E1020–E1032. doi: 10.1152/ajpendo.1990.258.6.E1020. [DOI] [PubMed] [Google Scholar]
- Bergman R. N., Phillips L. S., Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest. 1981 Dec;68(6):1456–1467. doi: 10.1172/JCI110398. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Botz C. K., Leibel B. S., Zingg W., Gander R. E., Albisser A. M. Comparison of peripheral and portal routes of insulin infusion by a computer-controlled insulin infusion system (artificial endocrine pancreas). Diabetes. 1976 Aug;25(8):691–700. doi: 10.2337/diab.25.8.691. [DOI] [PubMed] [Google Scholar]
- Christiansen E., Andersen H. B., Rasmussen K., Christensen N. J., Olgaard K., Kirkegaard P., Tronier B., Vølund A., Damsbo P., Burcharth F. Pancreatic beta-cell function and glucose metabolism in human segmental pancreas and kidney transplantation. Am J Physiol. 1993 Mar;264(3 Pt 1):E441–E449. doi: 10.1152/ajpendo.1993.264.3.E441. [DOI] [PubMed] [Google Scholar]
- Cobelli C., Mari A., Ferrannini E. Non-steady state: error analysis of Steele's model and developments for glucose kinetics. Am J Physiol. 1987 May;252(5 Pt 1):E679–E689. doi: 10.1152/ajpendo.1987.252.5.E679. [DOI] [PubMed] [Google Scholar]
- DeFronzo R. A., Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. 1991 Mar;14(3):173–194. doi: 10.2337/diacare.14.3.173. [DOI] [PubMed] [Google Scholar]
- Elahi D., Clark B. A., McAloon-Dyke M., Wong G., Brown R., Shapiro M., Minaker K. L., Flanagan T. L., Pruett T., Gingerich R. Islet cell responses to glucose in human transplanted pancreas. Am J Physiol. 1991 Dec;261(6 Pt 1):E800–E808. doi: 10.1152/ajpendo.1991.261.6.E800. [DOI] [PubMed] [Google Scholar]
- Elahi D., McAloon-Dyke M., Clark B. A., Kahn B. B., Weinreb J. E., Minaker K. L., Wong G. A., Morse L. A., Brown R. S., Shapiro M. E. Sequential evaluation of islet cell responses to glucose in the transplanted pancreas in humans. Am J Surg. 1993 Jan;165(1):15–22. doi: 10.1016/s0002-9610(05)80398-8. [DOI] [PubMed] [Google Scholar]
- Falholt K., Cutfield R., Alejandro R., Vølund A., Heding L. G., Mintz D. H. Influence of portal delivery of insulin on intracellular glucose and lipid metabolism. Metabolism. 1991 Feb;40(2):122–126. doi: 10.1016/0026-0495(91)90161-o. [DOI] [PubMed] [Google Scholar]
- Fischer U., Rizza R. A., Hall L. D., Westland R. E., Haymond M. W., Clemens A. H., Gerich J. E., Service F. J. Comparison of peripheral and portal venous insulin administration on postprandial metabolic responses in alloxan-diabetic dogs. Effects of identical preprogrammed complex insulin infusion waveforms. Diabetes. 1982 Jul;31(7):579–584. doi: 10.2337/diab.31.7.579. [DOI] [PubMed] [Google Scholar]
- Freyse E. J., Fischer U., Albrecht G., Marx S., Keilacker H. The effect of prehepatic insulin administration on alanine flux rates in diabetic dogs. Diabetologia. 1987 Jun;30(6):402–408. doi: 10.1007/BF00292542. [DOI] [PubMed] [Google Scholar]
- Goriya Y., Bahoric A., Marliss E. B., Zinman B., Albisser A. M. The metabolic and hormonal responses to a mixed meal in unrestrained pancreatectomised dogs chronically treated by portal or peripheral insulin infusion. Diabetologia. 1981 Jul;21(1):58–64. doi: 10.1007/BF03216226. [DOI] [PubMed] [Google Scholar]
- Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
- Homan M., Nicholson C. P., Katz H., Perkins J., Haymond M., Jensen M., Butler P., Rizza R. Effects of chronic systemic insulin delivery on insulin action in dogs. Diabetologia. 1991 Oct;34(10):702–708. doi: 10.1007/BF00401514. [DOI] [PubMed] [Google Scholar]
- Ishida T., Chap Z., Chou J., Lewis R. M., Hartley C. J., Entman M. L., Field J. B. Effects of portal and peripheral venous insulin infusion on glucose production and utilization in depancreatized, conscious dogs. Diabetes. 1984 Oct;33(10):984–990. doi: 10.2337/diab.33.10.984. [DOI] [PubMed] [Google Scholar]
- Jimenez J. T., Walford S., Home P. D., Hanning I., Alberti K. G. Free insulin levels and metabolic effects of meal-time bolus and square-wave intraperitoneal insulin infusion in insulin-dependent diabetic patients. Diabetologia. 1985 Oct;28(10):728–733. doi: 10.1007/BF00265019. [DOI] [PubMed] [Google Scholar]
- Katz H., Homan M., Velosa J., Robertson P., Rizza R. Effects of pancreas transplantation on postprandial glucose metabolism. N Engl J Med. 1991 Oct 31;325(18):1278–1283. doi: 10.1056/NEJM199110313251804. [DOI] [PubMed] [Google Scholar]
- Kendall D. M., Sutherland D. E., Najarian J. S., Goetz F. C., Robertson R. P. Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans. N Engl J Med. 1990 Mar 29;322(13):898–903. doi: 10.1056/NEJM199003293221305. [DOI] [PubMed] [Google Scholar]
- Kergoat M., Guerre-Millo M., Lauva M., Portha B. Increased insulin action in rats with mild insulin deficiency induced by neonatal streptozotocin. Am J Physiol. 1991 Apr;260(4 Pt 1):E561–E567. doi: 10.1152/ajpendo.1991.260.4.E561. [DOI] [PubMed] [Google Scholar]
- Kolterman O. G., Scarlett J. A., Olefsky J. M. Insulin resistance in non-insulin-dependent, type II diabetes mellitus. Clin Endocrinol Metab. 1982 Jul;11(2):363–388. doi: 10.1016/s0300-595x(82)80020-0. [DOI] [PubMed] [Google Scholar]
- Krusch D. A., Brown K. B., Cornett G., Freedlender A. E., Kaiser D. L., Hanks J. B. Insulin-dependent and insulin-independent effects after surgical alterations of the pancreas. Surgery. 1989 Jul;106(1):60–68. [PubMed] [Google Scholar]
- Kruszynska Y. T., Home P. D., Agius L., Alberti K. G. Hepatic glycogen metabolism and insulin receptor status after long-term peripheral insulin delivery in the islet-transplanted diabetic rat. Diabetes. 1986 Mar;35(3):306–310. doi: 10.2337/diab.35.3.306. [DOI] [PubMed] [Google Scholar]
- Kruszynska Y. T., Home P. D., McIntyre N. Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis. Hepatology. 1991 Jul;14(1):103–111. doi: 10.1002/hep.1840140117. [DOI] [PubMed] [Google Scholar]
- Kryshak E. J., Butler P. C., Marsh C., Miller A., Barr D., Polonsky K., Perkins J. D., Rizza R. A. Pattern of postprandial carbohydrate metabolism and effects of portal and peripheral insulin delivery. Diabetes. 1990 Feb;39(2):142–148. doi: 10.2337/diab.39.2.142. [DOI] [PubMed] [Google Scholar]
- Lickley H. L., Chisholm D. J., Rabinovitch A., Wexler M., Dupre J. Effects of portacaval anastomosis on glucose tolerance in the dog: evidence of an interaction between the gut and the liver in oral glucose dosposal. Metabolism. 1975 Oct;24(10):1157–1168. doi: 10.1016/0026-0495(75)90152-3. [DOI] [PubMed] [Google Scholar]
- Luzi L., Secchi A., Facchini F., Battezzati A., Staudacher C., Spotti D., Castoldi R., Ferrari G., Di Carlo V., Pozza G. Reduction of insulin resistance by combined kidney-pancreas transplantation in type 1 (insulin-dependent) diabetic patients. Diabetologia. 1990 Sep;33(9):549–556. doi: 10.1007/BF00404143. [DOI] [PubMed] [Google Scholar]
- Marangou A. G., Weber K. M., Boston R. C., Aitken P. M., Heggie J. C., Kirsner R. L., Best J. D., Alford F. P. Metabolic consequences of prolonged hyperinsulinemia in humans. Evidence for induction of insulin insensitivity. Diabetes. 1986 Dec;35(12):1383–1389. doi: 10.2337/diab.35.12.1383. [DOI] [PubMed] [Google Scholar]
- Marchesini G., Zoli M., Dondi C., Angiolini A., Forlani G., Melli A., Bianchi F. B., Pisi E. Glycémie et hormones de la glucorégulation au cours de la cirrhose. Etude du rythme circadien et du rôle des dérivations porto-systémiques. Gastroenterol Clin Biol. 1982 Mar;6(3):272–278. [PubMed] [Google Scholar]
- Nankervis A., Proietto J., Aitken P., Harewood M., Alford F. Differential effects of insulin therapy on hepatic and peripheral insulin sensitivity in Type 2 (non-insulin-dependent) diabetes. Diabetologia. 1982 Oct;23(4):320–325. doi: 10.1007/BF00253737. [DOI] [PubMed] [Google Scholar]
- Nauck M., Büsing M., Siegel E. G., Talartschik J., Baartz A., Baartz T., Hopt U. T., Becker H. D., Creutzfeldt W. Consequences of systemic venous drainage and denervation of heterotopic pancreatic transplants for insulin/C-peptide profiles in the basal state and after oral glucose. Diabetologia. 1991 Aug;34 (Suppl 1):S81–S85. doi: 10.1007/BF00587626. [DOI] [PubMed] [Google Scholar]
- Nelson J. A., Stephen R., Landau S. T., Wilson D. E., Tyler F. H. Intraperitoneal insulin administration produces a positive portal-systemic blood insulin gradient in unanesthetized, unrestrained swine. Metabolism. 1982 Oct;31(10):969–972. doi: 10.1016/0026-0495(82)90136-6. [DOI] [PubMed] [Google Scholar]
- Norwich K. H. Measuring rates of appearance in systems which are not in steady state. Can J Physiol Pharmacol. 1973 Feb;51(2):91–101. doi: 10.1139/y73-012. [DOI] [PubMed] [Google Scholar]
- Osei K., Cottrell D. A., Henry M. L., Tesi R. J., Ferguson R. M., O'Dorisio T. M. Insulin insensitivity and glucose effectiveness in type I diabetic allograft pancreas recipients. Transplant Proc. 1992 Jun;24(3):828–830. [PubMed] [Google Scholar]
- Petrides A. S., DeFronzo R. A. Glucose and insulin metabolism in cirrhosis. J Hepatol. 1989 Jan;8(1):107–114. doi: 10.1016/0168-8278(89)90169-4. [DOI] [PubMed] [Google Scholar]
- Radziuk J., Norwich K. H., Vranic M. Experimental validation of measurements of glucose turnover in nonsteady state. Am J Physiol. 1978 Jan;234(1):E84–E93. doi: 10.1152/ajpendo.1978.234.1.E84. [DOI] [PubMed] [Google Scholar]
- Radziuk J., Norwich K. H., Vranic M. Measurement and validation of nonsteady turnover rates with applications to the inulin and glucose systems. Fed Proc. 1974 Jul;33(7):1855–1864. [PubMed] [Google Scholar]
- Rizza R. A., Mandarino L. J., Gerich J. E. Dose-response characteristics for effects of insulin on production and utilization of glucose in man. Am J Physiol. 1981 Jun;240(6):E630–E639. doi: 10.1152/ajpendo.1981.240.6.E630. [DOI] [PubMed] [Google Scholar]
- Rosenlof L. K., Earnhardt R. C., Pruett T. L., Stevenson W. C., Douglas M. T., Cornett G. C., Hanks J. B. Pancreas transplantation. An initial experience with systemic and portal drainage of pancreatic allografts. Ann Surg. 1992 Jun;215(6):586–597. doi: 10.1097/00000658-199206000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Röjdmark S., Bloom G., Chou M. C., Field J. B. Hepatic extraction of exogenous insulin and glucagon in the dog. Endocrinology. 1978 Mar;102(3):806–813. doi: 10.1210/endo-102-3-806. [DOI] [PubMed] [Google Scholar]
- Schade D. S., Eaton R. P., Davis T., Akiya F., Phinney E., Kubica R., Vaughn E. A., Day P. W. The kinetics of peritoneal insulin absorption. Metabolism. 1981 Feb;30(2):149–155. doi: 10.1016/0026-0495(81)90164-5. [DOI] [PubMed] [Google Scholar]
- Sherwin R. S., Kramer K. J., Tobin J. D., Insel P. A., Liljenquist J. E., Berman M., Andres R. A model of the kinetics of insulin in man. J Clin Invest. 1974 May;53(5):1481–1492. doi: 10.1172/JCI107697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soeters P. B., Weir G., Ebeid A. M., Fischer J. E. Insulin, glucagon, portal systemic shunting, and hepatic failure in the dog. J Surg Res. 1977 Sep;23(3):183–188. doi: 10.1016/0022-4804(77)90019-1. [DOI] [PubMed] [Google Scholar]
- Stevenson R. W., Parsons J. A., Alberti K. G. Comparison of the metabolic responses to portal and peripheral infusions of insulin in diabetic dogs. Metabolism. 1981 Aug;30(8):745–752. doi: 10.1016/0026-0495(81)90019-6. [DOI] [PubMed] [Google Scholar]
- Wilczek H., Gunnarsson R., Felig P., Ostman J., Groth C. G., Wahren J. Normalization of hepatic glucose regulation despite systemic insulin delivery. Studies in patients with pancreatic transplantation for type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1991 May;34(5):345–349. doi: 10.1007/BF00405007. [DOI] [PubMed] [Google Scholar]
- van der Burg M. P., Gooszen H. G., Guicherit O. R., Jansen J. B., Frölich M., van Haastert F. A., Lamers C. B. Contribution of partial pancreatectomy, systemic hormone delivery, and duct obliteration to glucose regulation in canine pancreas. Importance in pancreas transplantation. Diabetes. 1989 Sep;38(9):1082–1089. [PubMed] [Google Scholar]