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

胰岛代谢疾病和 2 型糖尿病的蛋白质组学途径

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作者: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 Hum

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.

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