The S20G substitution in hIAPP is more amyloidogenic and cytotoxic than wild-type hIAPP in mouse islets

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• 作者：Daniel T. Meier ; Leon Entrup ; Andrew T. Templin ; Meghan F. Hogan…
• 关键词：Amylin ; Amyloid ; Beta cell ; Insulin secretion ; Islet ; Islet amyloid polypeptide ; Toxicity ; Type 2 diabetes
• 刊名：Diabetologia
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：59
• 期：10
• 页码：2166-2171
• 全文大小：506 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Internal Medicine
  Metabolic Diseases
  Human Physiology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0428
• 卷排序：59

文摘

Aims/hypothesisThe S20G human islet amyloid polypeptide (hIAPP) substitution is associated with an earlier onset of type 2 diabetes in humans. Studies of synthetic S20G hIAPP in cell-free systems and immortalised beta cells have suggested that this may be due to increased hIAPP amyloidogenicity and cytotoxicity. Thus, using primary islets from mice with endogenous S20G hIAPP expression, we sought to determine whether the S20G gene mutation leads to increased amyloid-induced toxicity, beta cell loss and reduced beta cell function.