Low density lipoprotein binding and uptake by human and rat islet beta cells.
Abnormalities in lipoprotein metabolism are common in diabetes. It is unknown whether variations in form or concentration of lipoproteins influence the function of pancreatic beta cells. This study investigates whether low density lipoproteins (LDL) exhibit specific interactions with islet beta 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 beta cells, as it was not detected on islet endocrine non-beta cells. At 37 C, LDL is taken up and lysosomally degraded by islet beta cells but not by islet non-beta 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 (2.10(7) vs. 2.10(8) per 10(3) 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 beta cells express LDL receptors that can internalize the lipoprotein. This pathway should be examined for its potential role in (dys)regulating pancreatic beta cell functions.
Grupping
A Y
AY
Department of Metabolism and Endocrinology, Vrije Universiteit Brussel, Belgium. agrup@mebo.vub.ac.be
Cnop
M
M
Van Schravendijk
C F
CF
Hannaert
J C
JC
Van Berkel
T J
TJ
Pipeleers
D G
DG
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000502:physiology
D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D000643:Ammonium Chloride; D002738:Chloroquine