Cell Surface Expression of LDL Receptor Is Decreased in Type 2 Diabetic Patients and Is Normalized by Insulin Therapy

Cell Surface Expression of LDL Receptor Is Decreased in Type 2 Diabetic Patients and Is Normalized by Insulin Therapy Laurence Duvillard , MD, PHD 1 , Emmanuel Florentin , PHD 1 , Gérard Lizard , PHD 1 , Jean-Michel Petit , MD 1 2 , Françoise Galland 2 , Serge Monier 1 , Philippe Gambert , MD, PHD 1 and Bruno Vergès , MD 1 2 1 Unity INSERM 498, Hôpital du Bocage, Dijon Cédex, France 2 Department of Endocrinology and Metabolic Diseases, Hôpital du Bocage, Dijon Cédex, France Abstract OBJECTIVE —In type 2 diabetic patients with poor metabolic control, kinetic studies have demonstrated that LDL fractional catabolic rate (FCR) is slowed down, whereas it is normalized on insulin therapy. This study was designed to analyze whether variations in the expression of LDL receptors at the cell surface could explain the results observed in kinetic studies. RESEARCH DESIGN AND METHODS —LDL receptors were quantified at the surface of mononuclear cells in fresh fasting blood samples by a flow cytometry method in 21 control subjects and 21 type 2 diabetic patients before and 3 months after the introduction of insulin therapy and concomitant removal of oral antidiabetic drugs. RESULTS —Before insulin treatment, monocyte LDL receptor expression was reduced by 41% (6,439 ± 2,310 vs. 10,846 ± 2,764 receptors per monocyte, P < 0.001) in type 2 diabetic patients compared with control subjects. It increased by 57% after 3 months of insulin therapy (10,096 ± 5,657 vs. 6,439 ± 2,310, P < 0.01) and was similar to that observed in control subjects. CONCLUSIONS —Our results suggest that insulin plays an important role in the in vivo expression of LDL receptors. Moreover, modulations in the expression of LDL receptors in type 2 diabetic patients either with poor metabolic control or on insulin therapy are likely to contribute to the variations of LDL FCR demonstrated by kinetic studies under those circumstances. FCR, fractional catabolic rate FITC, fluorescein isothiocyanate Footnotes Address correspondence and reprint requests to Laurence Duvillard, Unité INSERM 498, Hôpital du Bocage, BP 77908, 21079 Dijon Cédex, France. E-mail: laurence.duvillard{at}chu-dijon.fr . Received for publication 27 September 2002 and accepted in revised form 22 January 2003. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. DIABETES CARE