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Lipotoxicity reduce...
Lipotoxicity reduces beta cell survival through islet stellate cell activation regulated by lipid metabolism-related molecules
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- Zhou, Yunting (author)
- Southeast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China
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- Li, Wei (author)
- Southeast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China
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- Zhou, Junming (author)
- Nanjing Univ, Jingling Hosp, Dept Outpatient, Army Engn Univ, Nanjing, Jiangsu, Peoples R China
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- Chen, Juan (author)
- Southeast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China
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- Wang, Xiaohang (author)
- Southeast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China
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- Cai, Min (author)
- Southeast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China
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- Li, Fengfei (author)
- Nanjing Med Univ, Nanjing Hosp 1, Dept Endocrinol, Nanjing, Jiangsu, Peoples R China
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- Xu, Wei (author)
- Kings Coll London, Sch Life Course Sci, Dept Diabet, Guys Campus, London, England
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- Carlsson, Per-Ola (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Sun, Zilin (author)
- Southeast Univ, Inst Diabet, Sch Med, Zhongda Hosp,Dept Endocrinol, Nanjing, Jiangsu, Peoples R China
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(creator_code:org_t)
- ELSEVIER INC, 2019
- 2019
- English.
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In: Experimental Cell Research. - : ELSEVIER INC. - 0014-4827 .- 1090-2422. ; 380:1, s. 1-8
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Islet stellate cell
- Lipotoxicity
- beta cell
- Lipid metabolism
- SREBP-1c
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Zhou, Yunting
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Li, Wei
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Zhou, Junming
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Chen, Juan
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Wang, Xiaohang
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Cai, Min
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show more...
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Li, Fengfei
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Xu, Wei
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Carlsson, Per-Ol ...
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Sun, Zilin
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Experimental Cel ...
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Uppsala University