Journal of Clinical Endocrinology & Metabolism, Vol 78, 657-663, Copyright © 1994 by Endocrine Society

ARTICLES

Insulin receptor down-regulation and impaired antilipolytic action of insulin in diabetic patients after pancreas/kidney transplantation

G Boden, X Chen, J Ruiz, M Heifets, M Morris and F Badosa
Division of Endocrinology/Metabolism, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.

Patients with insulin-dependent diabetes who receive pancreas/kidney transplants lose their need for insulin injections, but they become hyperinsulinemic and insulin resistant, and sometimes develop noninsulin-dependent diabetes mellitus. The reason for the insulin resistance is not well understood. Specifically, it is not known whether they become resistant to the action of insulin on lipid metabolism. Euglycemic-hyperinsulinemic clamps were performed in six pancreas/kidney (P/K) recipients, six kidney (K) recipients (to control for immunosuppressive therapy), and eight healthy controls. Measured were leg blood flow (by plethysmography), rates of lipolysis (with [2H5] glycerol), fatty acid oxidation (by indirect calorimetry), fatty acid reesterification (with [2H5]glycerol and [1-13C]palmitate), monocyte membrane insulin binding (with [125I]Tyr-A14 insulin), and insulin receptor mass (by RIA). Fasting plasma insulin concentrations were 2 times higher in P/K and K recipients (108 pmol/L) than in controls (54 pmol/L). Insulin receptor mass in solubilized monocyte membranes from P/K and K recipients was reduced by 61% and 63%, respectively, whereas insulin binding was reduced by 73% and 70%, respectively. P/K and K recipients were resistant to the inhibitory action of insulin on lipolysis (P/K vs. controls, P < 0.01; K vs. controls, P < 0.02) and on fatty acid reesterification (P/K vs. controls, P < 0.02; K vs. controls, P < 0.03). P/K recipients appeared to be more resistant than K recipients, but the differences between the two groups were not statistically significant. We conclude that P/K recipients were hyperinsulinemic, had down-regulated the number of their monocyte insulin receptors, and were resistant to the antilipolytic action of insulin.

This article has been cited by other articles:

				S. Tiwari, N. Sharma, P. S. Gill, P. Igarashi, C. R. Kahn, J. B. Wade, and C. M. A. Ecelbarger Impaired sodium excretion and increased blood pressure in mice with targeted deletion of renal epithelial insulin receptor PNAS, April 29, 2008; 105(17): 6469 - 6474. [Abstract] [Full Text] [PDF]

				S. Tiwari, S. Riazi, and C. A. Ecelbarger Insulin's impact on renal sodium transport and blood pressure in health, obesity, and diabetes Am J Physiol Renal Physiol, October 1, 2007; 293(4): F974 - F984. [Abstract] [Full Text] [PDF]

				S. Tiwari, V. K.M. Halagappa, S. Riazi, X. Hu, and C. A. Ecelbarger Reduced Expression of Insulin Receptors in the Kidneys of Insulin-Resistant Rats J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2661 - 2671. [Abstract] [Full Text] [PDF]

				K. Bouzakri, H. K.R. Karlsson, H. Vestergaard, S. Madsbad, E. Christiansen, and J. R. Zierath IRS-1 Serine Phosphorylation and Insulin Resistance in Skeletal Muscle From Pancreas Transplant Recipients Diabetes, March 1, 2006; 55(3): 785 - 791. [Abstract] [Full Text] [PDF]

				G. Perseghin, A. Caumo, L. P. Sereni, A. Battezzati, and L. Luzi Fasting Blood Sample-Based Assessment of Insulin Sensitivity in Kidney-Pancreas-Transplanted Patients Diabetes Care, December 1, 2002; 25(12): 2207 - 2211. [Abstract] [Full Text] [PDF]

				A. Carpentier, B. W. Patterson, K. D. Uffelman, A. Giacca, M. Vranic, M. S. Cattral, and G. F. Lewis The Effect of Systemic Versus Portal Insulin Delivery in Pancreas Transplantation on Insulin Action and VLDL Metabolism Diabetes, June 1, 2001; 50(6): 1402 - 1413. [Abstract] [Full Text]

				E. Christiansen, A. Tibell, Aa. Volund, J. J. Holst, K. Rasmussen, L. Schaffer, and S. Madsbad Metabolism of Oral Glucose in Pancreas Transplant Recipients with Normal and Impaired Glucose Tolerance J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2299 - 2307. [Abstract] [Full Text] [PDF]