Abstract
The increasing incidence of type 2 diabetes mellitus is partially due to the rising obesity rates and the elevated levels of free fatty acids (FFAs). It is known that FFAs are putative mediators of beta-cell dysfunction, which is characterized with impaired glucose-stimulated insulin secretion and increased apoptosis, being defined as lipotoxicity. To date, many factors and their related signal pathways have been reported to be involved in FFA-induced beta-cell dysfunction. However, the entire blueprint is still not obtained. Some essential and newfound effectors, including the sterol regulatory element-binding protein (SREBP)-1c, farnesoid X receptor (FXR), forkhead box-containing protein O (FoxO) 1, ubiquitin C-terminal hydrolase L (UCHL) 1, N-myc downstream-regulated gene (NDRG) 2, perilipin family proteins, silent information regulator 2 protein 1 (Sirt1), pituitary adenylate cyclase-activating polypeptide (PACAP), and ghrelin are described in this review, which may help to further understand the molecular network for lipotoxicity.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Diabetes Mellitus, Type 2 / chemically induced*
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Diabetes Mellitus, Type 2 / genetics*
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Diabetes Mellitus, Type 2 / metabolism
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Diabetes Mellitus, Type 2 / physiopathology
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Forkhead Box Protein O1
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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Forkhead Transcription Factors / physiology
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Humans
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Insulin-Secreting Cells / drug effects
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Insulin-Secreting Cells / metabolism*
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Insulin-Secreting Cells / physiology
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Lipids / adverse effects*
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Lipids / pharmacology
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Models, Biological
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Cytoplasmic and Nuclear / physiology
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Signal Transduction / drug effects
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Signal Transduction / genetics*
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Signal Transduction / physiology
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Sterol Regulatory Element Binding Protein 1 / genetics
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Sterol Regulatory Element Binding Protein 1 / metabolism
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Sterol Regulatory Element Binding Protein 1 / physiology
Substances
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FOXO1 protein, human
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Lipids
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Receptors, Cytoplasmic and Nuclear
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Sterol Regulatory Element Binding Protein 1
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farnesoid X-activated receptor