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(American Journal of Pathology. 2000;156:237-244.)
© 2000 American Society for Investigative Pathology


Regular Articles

Endocytosis of Low-Density Lipoprotein by Human Pancreatic ß Cells and Uptake in Lipid-Storing Vesicles, Which Increase with Age

Miriam Cnop, Annick Grupping, Anne Hoorens, Luc Bouwens, Myriam Pipeleers-Marichal and Daniel Pipeleers

From the Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium

Studies with I125-labeled low-density lipoproteins (LDLs) have shown the presence of high-affinity LDL receptors on insulin-producing ß cells but not on neighboring {alpha} cells. By using gold-labeled lipoproteins, we demonstrate receptor-mediated endocytosis of LDLs and very low-density lipoproteins in rat and human ß cells. Specific for human ß cells is the fusion of LDL-containing endocytotic vesicles with lipid-storing vesicles (LSVs; diameter, 0.6–3.6 µm), which are absent in rodent ß cells. LSVs also occur in human pancreatic {alpha} and duct cells, but these sequester little gold-labeled LDL. In humans <25 years old, LSVs occupy 1% of the cytoplasmic surface area in ß, {alpha}, and duct cells. In humans >50 years old, LSV surface area in ß cells (11 ± 2% of cytoplasmic surface area) is fourfold higher than in {alpha} and duct cells and 10-fold higher than in ß cells at younger ages (P < 0.001); the mean LSV diameter in these ß cells (1.8 ± 0.04 µm) is larger than at younger ages (1.1 ± 0.2 µm; P < 0.005). Oil red O staining on pancreatic sections confirms that neutral lipids accumulate in ß cells of older donors. We conclude that human ß cells can incorporate LDL and very low-density lipoprotein material in LSVs. The marked increase in the LSV area of aging human ß cells raises the question whether it is caused by prolonged exposure to high lipoprotein levels such as occurs in Western populations and whether it is causally related to the higher risk for type 2 diabetes with aging.





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