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

Journal Article · · Journal of Proteome Research
 [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
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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 community 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.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC05-76RLO1830; 3-APF-2014-182-A-N; K99 DK090210; R01 DK067536; R01 DK074795; R01 DK103215
OSTI ID:
1287492
Journal Information:
Journal of Proteome Research, Vol. 14, Issue 8; ISSN 1535-3893
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 17 works
Citation information provided by
Web of Science

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Cited By (8)

m6A mRNA methylation regulates human β-cell biology in physiological states and in type 2 diabetes journal July 2019
Novel factors modulating human β-cell proliferation journal September 2016
In vivo phosphoproteomics reveals pathogenic signaling changes in diabetic islets posted_content October 2018
A proteomic signature that reflects pancreatic beta-cell function journal August 2018
Differential proteomic analysis of white adipose tissues from T2D KKAy mice by LC-ESI-QTOF journal March 2017
Forkhead box protein O1 (FoxO1) regulates hepatic serine protease inhibitor B1 (serpinB1) expression in a non-cell-autonomous fashion journal January 2019
β Cell dysfunction during progression of metabolic syndrome to type 2 diabetes journal August 2019
Imaging mass spectrometry enables molecular profiling of mouse and human pancreatic tissue journal April 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
insulin resistance
pancreatic islets
proteome
proliferation
metabolism
function