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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
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, 0.63.6 µm), which are absent in rodent
ß cells. LSVs also occur in human pancreatic
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,
, 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
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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