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- Zhou, YuntingSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (författare)
Lipotoxicity reduces beta cell survival through islet stellate cell activation regulated by lipid metabolism-related molecules
- Artikel/kapitelEngelska2019
Förlag, utgivningsår, omfång ...
- ELSEVIER INC,2019
- printrdacarrier
Nummerbeteckningar
- LIBRIS-ID:oai:DiVA.org:uu-384985
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-384985URI
- https://doi.org/10.1016/j.yexcr.2019.04.012DOI
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- Språk:engelska
- Sammanfattning på:engelska
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Anmärkningar
- Background: Islet stellate cells (ISCs) activation is mainly associated with islet fibrosis, which contributes to the progression of type 2 diabetes. However, the molecular mechanism underlying this process is not fully understood.Methods: In order to investigate this process the current study examined ectopic fat accumulation in rats with high-fat diet (HFD) induced obesity. Levels of lipotoxicity-induced ISC activation and islet function were assessed via intraperitoneal glucose and insulin tolerance tests, and immunohistochemistry. The expression of lipid metabolism- and ISC activation-related markers was evaluated in cultured ISCs treated with palmitic acid (PA) using quantitative PCR and western blotting. We also overexpressed sterol regulatory element-binding protein (SREBP)-1c in ISCs by lentiviral transduction, and assessed the effects on insulin release in co-cultures with isolated rat islets.Results: HFD increased body weight and ectopic fat accumulation in pancreatic islets. Lipotoxicity caused progressive glucose intolerance and insulin resistance, upregulated a-smooth muscle actin, and stimulated the secretion of extracellular matrix. Lipotoxicity reduced the expression of lipid metabolism-related molecules in ISCs treated with PA, especially SREBP-1c. Overexpression of SREBP-1c in ISCs improved islet viability and insulin secretion in co-cultures.Conclucions: These results indicate that lipotoxicity-induced ISC activation alters islet function via regulation of lipid metabolism, suggesting that therapeutic strategies targeting activated ISC may be an effective treatment for prevention of ISC activation-associated islet dysfunction.
Ämnesord och genrebeteckningar
- MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
- MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
- Islet stellate cell
- Lipotoxicity
- beta cell
- Lipid metabolism
- SREBP-1c
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Li, WeiSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (författare)
- Zhou, JunmingNanjing Univ, Jingling Hosp, Dept Outpatient, Army Engn Univ, Nanjing, Jiangsu, Peoples R China (författare)
- Chen, JuanSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (författare)
- Wang, XiaohangSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (författare)
- Cai, MinSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (författare)
- Li, FengfeiNanjing Med Univ, Nanjing Hosp 1, Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (författare)
- Xu, WeiKings Coll London, Sch Life Course Sci, Dept Diabet, Guys Campus, London, England (författare)
- Carlsson, Per-OlaUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)perocarl (författare)
- Sun, ZilinSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (författare)
- Southeast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R ChinaNanjing Univ, Jingling Hosp, Dept Outpatient, Army Engn Univ, Nanjing, Jiangsu, Peoples R China (creator_code:org_t)
Sammanhörande titlar
- Ingår i:Experimental Cell Research: ELSEVIER INC380:1, s. 1-80014-48271090-2422
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