Endocytosis of low-density lipoprotein by human pancreatic beta cells and uptake in lipid-storing vesicles, which increase with age.
Studies with I(125)-labeled low-density lipoproteins (LDLs) have shown the presence of high-affinity LDL receptors on insulin-producing beta 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 beta cells. Specific for human beta cells is the fusion of LDL-containing endocytotic vesicles with lipid-storing vesicles (LSVs; diameter, 0.6-3.6 microm), which are absent in rodent beta 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 beta, alpha, and duct cells. In humans >50 years old, LSV surface area in beta cells (11 +/- 2% of cytoplasmic surface area) is fourfold higher than in alpha and duct cells and 10-fold higher than in beta cells at younger ages (P < 0.001); the mean LSV diameter in these beta cells (1.8 +/- 0.04 microm) is larger than at younger ages (1.1 +/- 0.2 microm; P < 0.005). Oil red O staining on pancreatic sections confirms that neutral lipids accumulate in beta cells of older donors. We conclude that human beta cells can incorporate LDL and very low-density lipoprotein material in LSVs. The marked increase in the LSV area of aging human beta 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.
Cnop
M
M
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
Grupping
A
A
Hoorens
A
A
Bouwens
L
L
Pipeleers-Marichal
M
M
Pipeleers
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002675:Child, Preschool; D046508:Culture Techniques; D004705:Endocytosis / Q000502:physiology*; D005260:Female; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000502:physiology*; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar
D008077:Lipoproteins, LDL