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  • Zhou, YuntingSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (author)

Lipotoxicity reduces beta cell survival through islet stellate cell activation regulated by lipid metabolism-related molecules

  • Article/chapterEnglish2019

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  • ELSEVIER INC,2019
  • printrdacarrier

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  • 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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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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  • 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.

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  • Li, WeiSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (author)
  • Zhou, JunmingNanjing Univ, Jingling Hosp, Dept Outpatient, Army Engn Univ, Nanjing, Jiangsu, Peoples R China (author)
  • Chen, JuanSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (author)
  • Wang, XiaohangSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (author)
  • Cai, MinSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (author)
  • Li, FengfeiNanjing Med Univ, Nanjing Hosp 1, Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (author)
  • Xu, WeiKings Coll London, Sch Life Course Sci, Dept Diabet, Guys Campus, London, England (author)
  • Carlsson, Per-OlaUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)perocarl (author)
  • Sun, ZilinSoutheast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China (author)
  • 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)

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  • In:Experimental Cell Research: ELSEVIER INC380:1, s. 1-80014-48271090-2422

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Zhou, Yunting
Li, Wei
Zhou, Junming
Chen, Juan
Wang, Xiaohang
Cai, Min
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Xu, Wei
Carlsson, Per-Ol ...
Sun, Zilin
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MEDICAL AND HEALTH SCIENCES
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