Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet

Belinda Yau; Sheyda Naghiloo; Alexis Diaz-Vegas; Austin V Carr; Julian Van Gerwen; Elise J Needham; Dillon Jevon; Sing-Young Chen; Kyle L Hoehn; Amanda E Brandon; Laurance Macia; Gregory J Cooney; Michael R Shortreed; Lloyd M Smith; Mark P Keller; Peter Thorn; Mark Larance; David E James; Sean J Humphrey; Melkam A Kebede

doi:10.1016/j.isci.2021.103099

Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet

iScience. 2021 Sep 9;24(10):103099. doi: 10.1016/j.isci.2021.103099. eCollection 2021 Oct 22.

Authors

Belinda Yau¹, Sheyda Naghiloo¹, Alexis Diaz-Vegas², Austin V Carr³, Julian Van Gerwen², Elise J Needham², Dillon Jevon¹, Sing-Young Chen⁴, Kyle L Hoehn^{4

5}, Amanda E Brandon¹, Laurance Macia¹, Gregory J Cooney¹, Michael R Shortreed³, Lloyd M Smith³, Mark P Keller⁶, Peter Thorn¹, Mark Larance², David E James^{1

2}, Sean J Humphrey², Melkam A Kebede¹

Affiliations

¹ Discipline of Physiology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Camperdown 2006, Australia.
² School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.
³ Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
⁴ Department of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW 2052, Australia.
⁵ Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
⁶ Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.

Abstract

Pancreatic islets are essential for maintaining physiological blood glucose levels, and declining islet function is a hallmark of type 2 diabetes. We employ mass spectrometry-based proteomics to systematically analyze islets from 9 genetic or diet-induced mouse models representing a broad cross-section of metabolic health. Quantifying the islet proteome to a depth of >11,500 proteins, this study represents the most detailed analysis of mouse islet proteins to date. Our data highlight that the majority of islet proteins are expressed in all strains and diets, but more than half of the proteins vary in expression levels, principally due to genetics. Associating these varied protein expression levels on an individual animal basis with individual phenotypic measures reveals islet mitochondrial function as a major positive indicator of metabolic health regardless of strain. This compendium of strain-specific and dietary changes to mouse islet proteomes represents a comprehensive resource for basic and translational islet cell biology.

Keywords: animal physiology; diabetology; proteomics.

Grants and funding

R01 CA193481/CA/NCI NIH HHS/United States