Abstract | OBJECTIVE: The reduction in insulin secretory capacity and beta-cell mass has been attributed, at least partially, to lipotoxicity, which may contribute to the development of type 2 diabetes. Chronic free fatty acids (FFA) exposure impairs pancreatic beta-cell function and induces beta-cell apoptosis. This study is to elucidate the underlying molecular mechanisms. RESEARCH DESIGN AND METHODS: RESULTS: FFA treatment resulted in SREBP-1c overexpression, impaired GSIS, lipid accumulation, apoptosis of INS-1E cells. In addition, the expression of lipogenic genes and UCP-2 were upregulated, but AMPK, IRS-2, PDX-1, GLUT-2 and Bcl-2 were downregulated in the exposed cells. However, these lipotoxic effects of FFA were largely prevented by induction of a SREBP-1c small interfering RNA. CONCLUSIONS: These data suggest a strong correlation between FFA treatment and SREBP-1c activation in INS-1E cells. SREBP-1c might be a major factor responsible for beta-cell lipotoxicity, and SREBP-1c knockdown could protect INS-1E cells from lipotoxicity, which is implicating a therapeutic potential for treating diabetes related to lipotoxicity.
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Authors | J Li, X Liu, X Ran, J Chen, X Li, W Wu, H Huang, H Huang, Y Long, J Liang, J Cheng, H Tian |
Journal | Diabetes, obesity & metabolism
(Diabetes Obes Metab)
Vol. 12
Issue 1
Pg. 35-46
(Jan 2010)
ISSN: 1463-1326 [Electronic] England |
PMID | 19758361
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Fatty Acids, Nonesterified
- Insulin
- Palmitates
- RNA, Small Interfering
- Sterol Regulatory Element Binding Protein 1
- Triglycerides
- Oleic Acid
- Glucose
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Topics |
- Animals
- Apoptosis
(physiology)
- Blotting, Western
- Cell Line
- Diabetes Mellitus, Type 2
(metabolism)
- Fatty Acids, Nonesterified
(pharmacology)
- Gene Expression
- Gene Knockdown Techniques
- Glucose
(pharmacology)
- Humans
- Insulin
(metabolism)
- Insulin Secretion
- Insulin-Secreting Cells
(cytology, drug effects, metabolism)
- Lipid Metabolism
(physiology)
- Oleic Acid
(pharmacology)
- Palmitates
(pharmacology)
- RNA, Small Interfering
(isolation & purification)
- Sterol Regulatory Element Binding Protein 1
(genetics, metabolism)
- Transcription, Genetic
(drug effects)
- Triglycerides
(isolation & purification)
- Up-Regulation
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