title: Compensatory Islet Response to Insulin Resistance Revealed by Quantitative Proteomics.
abstract: 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-MS/MS and quantified ~1100 islet proteins (at least two peptides) with a false discovery rate < 1%. Significant alterations in abundance were observed for ~350 proteins among groups. The 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 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 β-cell mass in patients with diabetes. The data are available via the MassIVE repository, under accession no. MSV000079093.
authors.affiliation: Islet Cell & Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Abdelfattah
authors.initials: A
authors.lastname: El Ouaamari
authors.affiliation: Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Zhou
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Chong Wee
authors.initials: CW
authors.lastname: Liew
authors.affiliation: Islet Cell & Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Jun
authors.initials: J
authors.lastname: Shirakawa
authors.affiliation: Islet Cell & Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Ercument
authors.initials: E
authors.lastname: Dirice
authors.affiliation: Islet Cell & Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gedeon
authors.affiliation: Islet Cell & Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Sevim
authors.initials: S
authors.lastname: Kahraman
authors.affiliation: Islet Cell & Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Dario F
authors.initials: DF
authors.lastname: De Jesus
authors.affiliation: Islet Cell & Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Shweta
authors.initials: S
authors.lastname: Bhatt
authors.affiliation: Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352.
authors.forename: Jong-Seo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352.
authors.forename: Therese Rw
authors.initials: TR
authors.lastname: Clauss
authors.affiliation: Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352.
authors.forename: David G
authors.initials: DG
authors.lastname: Camp
authors.affiliation: Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.affiliation: Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Qian
authors.affiliation: Islet Cell & Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Rohit N
authors.initials: RN
authors.lastname: Kulkarni
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002853:Chromatography, Liquid; D059305:Diet, High-Fat; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008969:Molecular Sequence Data; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D020543:Proteome
keywords: Insulin resistance; function; metabolism; pancreatic islets; proliferation; proteome