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

Guenther Boden, Xinhua Chen, Jose Ruiz, Michael Heifets, Michael Morris, Francisco Badosa

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)657-663
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume78
Issue number3
DOIs
StatePublished - Mar 1994

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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