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,
Laurence 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
Affiliations
Belinda Yau
Discipline of Physiology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Camperdown 2006, Australia
Sheyda Naghiloo
Discipline of Physiology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Camperdown 2006, Australia
Alexis Diaz-Vegas
School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
Austin V. Carr
Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA
Julian Van Gerwen
School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
Elise J. Needham
School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
Dillon Jevon
Discipline of Physiology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Camperdown 2006, Australia
Sing-Young Chen
Department of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW 2052, Australia
Kyle L. Hoehn
Department of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW 2052, Australia; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA
Amanda E. Brandon
Discipline of Physiology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Camperdown 2006, Australia
Laurence Macia
Discipline of Physiology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Camperdown 2006, Australia
Gregory J. Cooney
Discipline of Physiology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Camperdown 2006, Australia
Michael R. Shortreed
Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA
Lloyd M. Smith
Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA
Mark P. Keller
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA
Peter Thorn
Discipline of Physiology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Camperdown 2006, Australia
Mark Larance
School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
David E. James
Discipline of Physiology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Camperdown 2006, Australia; School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
Sean J. Humphrey
School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia; Corresponding author
Melkam A. Kebede
Discipline of Physiology, School of Medical Sciences, Charles Perkins Centre, University of Sydney, Camperdown 2006, Australia; Corresponding author
Summary: 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.
