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Title: Compensatory islet response to insulin resistance revealed by quantitative proteomics

Compensatory islet response is a distinct feature of the pre-diabetic insulin resistant state in humans and rodents. To identify alterations in the islet proteome that characterize the adaptive response, we analyzed islets from five-month-old male control, high-fat diet fed (HFD) or obese ob/ob mice by LC-MS(/MS) and quantified ~1,100 islet proteins (at least two peptides) with a false discovery rate <1%. Significant alterations in abundance were observed for ~350 proteins between groups. A majority of alterations were common to both models, and the changes of a subset of ~40 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 conclusion, 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. In conclusion, these data provide a valuable resource of candidate proteins to the scientific communitymore » to undertake further studies aimed at enhancing β-cell mass in patients with diabetes. The data are available via the MassIVE repository, with accession MSV000079093.« less
 [1] ;  [2] ;  [3] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [2] ;  [2] ;  [2] ;  [2] ;  [1]
  1. Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States). Joslin Diabetes Center
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Biological Sciences Division, and Environmental Molecular Sciences Lab. (EMSL)
  3. Univ. of Illinois at Chicago, Chicago, IL (United States). Dept. of Physiology and Biophysics
Publication Date:
Grant/Contract Number:
AC05-76RLO1830; 3-APF-2014-182-A-N; K99 DK090210; R01 DK067536; R01 DK074795; R01 DK103215
Accepted Manuscript
Journal Name:
Journal of Proteome Research
Additional Journal Information:
Journal Volume: 14; Journal Issue: 8; Journal ID: ISSN 1535-3893
American Chemical Society (ACS)
Research Org:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; insulin resistance; pancreatic islets; proteome; proliferation; metabolism; function
OSTI Identifier: