Compensatory Islet Response to Insulin Resistance Revealed by Quantitative Proteomics

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• 作者：Abdelfattah El Ouaamari ; Jian-Ying Zhou ; Chong Wee Liew ; Jun Shirakawa ; Ercument Dirice ; Nicholas Gedeon ; Sevim Kahraman ; Dario F. De Jesus ; Shweta Bhatt ; Jong-Seo Kim ; Therese R. W. Clauss ; David G. Camp ; II ; Richard D. Smith ; Wei-Jun Qian ; Rohit N. Kulkarni
• 刊名：Journal of Proteome Research
• 出版年：2015
• 出版时间：August 7, 2015
• 年：2015
• 卷：14
• 期：8
• 页码：3111-3122
• 全文大小：562K
• ISSN：1535-3907

文摘

Compensatory islet response is a distinct feature of the prediabetic insulin-resistant state in humans and rodents. To identify alterations in the islet proteome that characterize the adaptive response, we analyzed islets from 5 month old male control, high-fat diet fed (HFD), or obese ob/ob mice by LC鈥揗S/MS and quantified 鈭?100 islet proteins (at least two peptides) with a false discovery rate < 1%. Significant alterations in abundance were observed for 鈭?50 proteins among groups. The majority of alterations were common to both models, and the changes of a subset of 鈭?0 proteins and 12 proteins were verified by targeted quantification using selected reaction monitoring and western blots, respectively. The insulin-resistant islets in both groups exhibited reduced expression of proteins controlling energy metabolism, oxidative phosphorylation, hormone processing, and secretory pathways. Conversely, an increased expression of molecules involved in protein synthesis and folding suggested effects in endoplasmic reticulum stress response, cell survival, and proliferation in both insulin-resistant models. In summary, we report a unique comparison of the islet proteome that is focused on the compensatory response in two insulin-resistant rodent models that are not overtly diabetic. These data provide a valuable resource of candidate proteins to the scientific community to undertake further studies aimed at enhancing 尾-cell mass in patients with diabetes. The data are available via the MassIVE repository, under accession no. MSV000079093.