Cholesterol induces mitochondrial dysfunction and apoptosis in mouse pancreatic beta-cell line MIN6 cells.
Reduction of pancreatic β-cell mass is a key element leading to type 2 diabetes. Obesity and overweight with high levels of lipids including cholesterol are tightly linked to type 2 diabetes. The direct impact of cholesterol on pancreatic β-cells, however, has not been extensively studied. In this study, MIN6 mouse β-cell line was used to test the effect of cholesterol on pancreatic β-cell apoptosis over different doses and durations. It was found that cholesterol dose- and time-dependently induced cell death of MIN6 cells above 160 μM after 6 h treatment in vitro. Annexin-V staining revealed that cholesterol treatment significantly induced apoptosis in MIN6 cells. Cholesterol treatment resulted in the loss of the ability to retain Rhodamine 123, indicating mitochondrial damage in MIN6 cells. Cholesterol-induced cell apoptosis and mitochondrial damage were blocked by low-temperature condition. In addition, glutathione also protected MIN6 cells from cholesterol-induced cell death. It is concluded that high level of cholesterol induces cell apoptosis in MIN6 cells, which is in part due to mitochondrial dysfunction. We suggest that excessive uptake of cholesterol in β-cells may contribute to β-cell apoptosis and dysfunction and the deterioration of type 2 diabetes.
Zhao
Yu-Feng
YF
School of Biomedical Sciences, The University of Queensland, St Lucia, QLD 4072, Australia.
Wang
Li
L
Lee
Soohyun
S
Sun
Qiang
Q
Tuo
Ya
Y
Wang
Yuemin
Y
Pei
Jianming
J
Chen
Chen
C
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D002784:Cholesterol / Q000378:metabolism*; D003080:Cold Temperature; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D005978:Glutathione / Q000378:metabolism; D006937:Hypercholesterolemia / Q000503:physiopathology; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000453:epidemiology; D051336:Mitochondrial Membranes; D009994:Osmolar Concentration; D010539:Permeability; D013997:Time Factors
D017304:Annexin A5; D002784:Cholesterol; D005978:Glutathione