Role of Cisd2 in Pancreatic β Islet Function

• Main Authors: Shao-Yu Hsiung, 熊少瑜
• Other Authors: Ting-Fen Tsai
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/mjxv26

碩士 === 國立陽明大學 === 生命科學系暨基因體科學研究所 === 102 === CISD2, CDGSH iron sulfur domain 2, is the causative gene of Wolfram syndrome 2 (WFS2) in human. The CISD2 gene is an evolutionarily conserved novel gene, encoding a transmembrane protein localized to ER and mitochondrial outer membrane. Cisd2 knockout (KO) mice exhibit neuron degeneration, optic nerve atrophy and premature ageing which are similar to clinical symptoms of Wolfram syndrome patients. Wolfram syndrome is also called DIDMOAD that shows feature of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. In this study, we investigate the effects of Cisd2 deficiency on pancreatic endocrine function by high-fat diet (HFD) treatment. Surprisingly, there is no increase in body weight of HFD-fed Cisd2 KO mice. Cisd2 KO mice use the lipid as one of the energy sources in much higher proposition for the correspondingly increased energy expenditure than that in wild-type (WT) mice. Compared to WT mice, Cisd2 KO mice have greater glucose tolerance, higher insulin sensitivity and normoglycemia after HFD treatment. In WT mice, there was an increase of serum insulin in response to insulin resistance induced by HFD treatment; however, serum insulin did not increase in the HFD-fed Cisd2 KO mice. Furthermore, immunohistochemistry (IHC) staining of insulin revealed that the islet size of Cisd2 KO reduced and the ratio of insulin positive cell in islet decreased. Additionally, TEM analysis showed less secretory granules formation and ER dilation in -cell. In conclusion, losses of Cisd2 function showed protect effects from HFD treatment through elevation of energy expenditure. However, islet morphology of Cisd2 KO mice has tendency toward to diabetes morphology. These data indicate that Cisd2 KO mice could be used as an animal model to understand the pathophysiological of WFS2.