Cholesterol metabolism and pancreatic beta-cell function.
OBJECTIVE
It has recently been recognized that cholesterol homeostasis is fundamentally important for appropriate insulin secretory function of beta-cells in the pancreas. This review summarizes recent advances in understanding the relationship between beta-cell cholesterol metabolism and beta-cell function.


RESULTS
The accumulation of cholesterol in beta-cells causes perturbations in glucose metabolism, reduces insulin secretion and can be associated with a diabetic phenotype. Cholesterol is also a key determinant of beta-cell membrane organization and cell survival. The ATP-binding cassette transporter A1, which effluxes cholesterol to lipid-free/lipid-poor apolipoprotein A-I, the principal apolipoprotein in HDLs, is crucial for maintaining beta-cell cholesterol homeostasis and function. There is also evidence suggesting that different lipoprotein classes have varying effects on beta-cell function and survival.


CONCLUSIONS
Cholesterol is important for beta-cell function and survival. It can cause beta-cell loss if allowed to accumulate in the cells in an unregulated manner. The maintenance of beta-cell cholesterol homeostasis, therefore, is important for preventing beta-cell dysfunction, the onset of insulin resistance and the development of type 2 diabetes.
Lipid Research Group, The Heart Research Institute, New South Wales, Australia.
Michelle
M
Fryirs
Philip J
PJ
Barter
Kerry-Anne
KA
Rye
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008074:Lipoproteins / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D008074:Lipoproteins; D002784:Cholesterol