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Low Density Lipoprotein Binding and Uptake by Human and Rat Islet ß Cells¹

Department of Metabolism and Endocrinology (A.Y.G., M.C., C.F.H.V.S., J.C.H., D.G.P.), Vrije Universiteit Brussel, Belgium; and Division of Biopharmaceutics (Th.J.C.V.B.), Center for Bio-Pharmaceutical Sciences, Sylvius Laboratory, University of Leiden, The Netherlands

Address all correspondence and requests for reprints to: A. Y. Grupping, Department of Metabolism and Endocrinology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussel, Belgium. E-mail: agrup{at}mebo.vub.ac.be

Abnormalities in lipoprotein metabolism are common in diabetes. It is unknown whether variations in form or concentration of lipoproteins influence the function of pancreatic ß cells. This study investigates whether low density lipoproteins (LDL) exhibit specific interactions with islet ß cells. Radioactively labeled LDL (¹²⁵I-LDL) and fluorescently labeled LDL (DiI-LDL) were used as tracers. Rat islet cells express high affinity LDL binding sites (K_d = 9 nM), which are also recognized by very low density lipoproteins and which are down-regulated by LDL. Binding of LDL appears restricted to the ß cells, as it was not detected on islet endocrine non-ß cells. At 37 C, LDL is taken up and lysosomally degraded by islet ß cells but not by islet non-ß cells. Human islet cells were also found to present LDL binding, uptake, and degradation. Compared with rat islet cells, human islet cells exhibit 10-fold less binding sites (2.10⁷ vs. 2.10⁸ per 10³ cells) with a 2-fold lower K_d value (5 nM) and an equal sensitivity to LDL-induced down-regulation. In conclusion, human and rat islet ß cells express LDL receptors that can internalize the lipoprotein. This pathway should be examined for its potential role in (dys)regulating pancreatic ß cell functions.

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