Dataset Information

Peroxisome-generated hydrogen peroxide as important mediator of lipotoxicity in insulin-producing cells.

ABSTRACT:

Objective

Type 2 diabetes is a complex disease that is accompanied by elevated levels of nonesterified fatty acids (NEFAs), which contribute to ?-cell dysfunction and ?-cell loss, referred to as lipotoxicity. Experimental evidence suggests that oxidative stress is involved in lipotoxicity. In this study, we analyzed the molecular mechanisms of reactive oxygen species-mediated lipotoxicity in insulin-producing RINm5F cells and INS-1E cells as well as in primary rat islet cells.

Research design and methods

The toxicity of saturated NEFAs with different chain lengths upon insulin-producing cells was determined by MTT and propidium iodide (PI) viability assays. Catalase or superoxide dismutase overexpressing cells were used to analyze the nature and the cellular compartment of reactive oxygen species formation. With the new H?O?-sensitive fluorescent protein HyPer H?O? formation induced by exposure to palmitic acid was determined.

Results

Only long-chain (>C14) saturated NEFAs were toxic to insulin-producing cells. Overexpression of catalase in the peroxisomes and in the cytosol, but not in the mitochondria, significantly reduced H?O? formation and protected the cells against palmitic acid-induced toxicity. With the HyPer protein, H?O? generation was directly detectable in the peroxisomes of RINm5F and INS-1E insulin-producing cells as well as in primary rat islet cells.

Conclusions

The results demonstrate that H?O? formation in the peroxisomes rather than in the mitochondria are responsible for NEFA-induced toxicity. Therefore, we propose a new concept of fatty acid-induced ?-cell lipotoxicity mediated via reactive oxygen species formation through peroxisomal ?- oxidation.

SUBMITTER: Elsner M

PROVIDER: S-EPMC3012172 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Publications

Peroxisome-generated hydrogen peroxide as important mediator of lipotoxicity in insulin-producing cells.

Elsner Matthias M Gehrmann Wiebke W Lenzen Sigurd S

Diabetes 20101022 1

<h4>Objective</h4>Type 2 diabetes is a complex disease that is accompanied by elevated levels of nonesterified fatty acids (NEFAs), which contribute to β-cell dysfunction and β-cell loss, referred to as lipotoxicity. Experimental evidence suggests that oxidative stress is involved in lipotoxicity. In this study, we analyzed the molecular mechanisms of reactive oxygen species-mediated lipotoxicity in insulin-producing RINm5F cells and INS-1E cells as well as in primary rat islet cells.<h4>Researc ...[more]

PMID: 20971967

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Dataset Information

Peroxisome-generated hydrogen peroxide as important mediator of lipotoxicity in insulin-producing cells.

Objective

Research design and methods

Results

Conclusions

Publications

Peroxisome-generated hydrogen peroxide as important mediator of lipotoxicity in insulin-producing cells.

Similar Datasets

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