Signaling molecules involved in lipid-induced pancreatic beta-cell dysfunction.
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.
Division of Endocrinology, Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, People's Republic of China.
Shiying
S
Shao
Yan
Y
Yang
Gang
G
Yuan
Muxun
M
Zhang
Xuefeng
X
Yu
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008055:Lipids / Q000009:adverse effects* / Q000494:pharmacology; D008954:Models, Biological; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000099150:Receptor, Farnesoid X-Activated
D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D008055:Lipids; D018160:Receptors, Cytoplasmic and Nuclear; D051780:Sterol Regulatory Element Binding Protein 1; D000099150:Receptor, Farnesoid X-Activated; C085126:FOXO1 protein, human