Cholesterol toxicity in pancreatic islets from LDL receptor-deficient mice

Souza, J. C.; Oliveira, Camila Aparecida Machado de; Carneiro, E. M.; Boschero, Antônio Carlos; Oliveira, Helena Coutinho Franco de

doi:10.1007/s00125-010-1868-8

Cited by 6 publications

(5 citation statements)

References 3 publications

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“…For example, ATP-binding cassette transporter, subfamily A, member 1 (ABCA1) is a cellular cholesterol transporter. It was reported that the absence of ABCA1 in β cells results in decreased exocytosis of insulin, and also results in decreased cholesterol efflux and accumulation of cholesterol in the plasma membrane (Brunham et al 2007;de Souza et al 2010). These studies indicate that cholesterol is an important factor in mediating the toxic effect of LDL on β cells.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 78%

Cholesterol induces pancreatic β cell apoptosis through oxidative stress pathway

Liu

Hou

et al. 2011

Cell Stress and Chaperones

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Type 2 diabetes is often associated with high blood cholesterol. Here, we investigated the effect of cholesterol loading on MIN6 cells derived from pancreatic β cells. Exposure of MIN6 cells to cholesterol-induced apoptosis in time-and dose-dependent manner. Treatment with methyl-β-cyclodextrin that removes cholesterol from plasma membrane prevented the cells from cholesterolinduced apoptosis. Western blot analysis revealed that the levels of phosphorylated-p38 mitogen-activated protein kinase (P-p38 MAPK) and c-Jun N-terminal kinases (P-JNK) were significantly increased after the cholesterol loading, suggesting that the stress-activated protein kinase signaling was stimulated. A specific p38 inhibitor rescued MIN6 cells from cholesterol-induced apoptosis, while JNK inhibitor failed, suggesting the importance of activation of p38 MAPK signaling in response to cholesterol. The expression of Bip and CHOP, the endoplasmic reticulum (ER) stress markers, remained unaffected, indicating that the ER stress may not be involved in the cytotoxicity of cholesterol on the MΙΝ6 cells. The intracellular concentration of reactive oxygen species measured by use of 2′,7′-dichlorofluorescin diacetate was significantly increased after cholesterol loading, demonstrating the induced apoptosis was mediated through oxidative stress. Addition of reduced form of glutathione in the medium rescued MIN6 cells from apoptosis induced by cholesterol loading. Taken together, these results demonstrate that the free cholesterol loading can induce apoptosis of MIN6 cells mediated by oxidative stress and the activation of p38 MAPK signaling.

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Section: Electronic Supplementary Materialsmentioning

confidence: 78%

Cholesterol induces pancreatic β cell apoptosis through oxidative stress pathway

Liu

Hou

et al. 2011

Cell Stress and Chaperones

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“…A cholesterol-rich diet did not affect glucose tolerance in a LDL receptor-deficient mouse (11). However, studies in pancreatic cell lines and isolated pancreatic islets showed that hypercholesterolemia may impair ␤-cell function and insulin response to glucose (2,5,10). In humans, the link between atherosclerosis and metabolic disorders is of particular interest.…”

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confidence: 99%

Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models

Laplante

Charbonneau

Avramoglu

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…To the Editor: In their letter [1], de Souza and colleagues point out important differences between our study [2] and their subsequent report on the role of the LDL receptor (LDLr) in islet cholesterol handling. In contrast to their data [3], we did not detect a significant difference between islet cholesterol levels in mice lacking LDLr (Ldlr -/-) and control mice [2].…”

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confidence: 72%

“…However, the results of both groups point to the ability of circulating and cellular cholesterol to significantly influence islet function. If islet cholesterol levels in Ldlr -/-mice are the result of a gradient-driven cholesterol flow from the plasma to the cell membranes associated with de novo cholesterol synthesis, as suggested by de Souza et al [1], increased plasma cholesterol levels would result in increased cholesterol levels in islets. However, a Western-type diet did not result in increased islet cholesterol levels in islets isolated from Ldlr -/-mice, despite the presence of severe hypercholesterolaemia.…”

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confidence: 87%