Dataset Information

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

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.

SUBMITTER: Yau B

PROVIDER: S-EPMC8479695 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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

Yau Belinda B Naghiloo Sheyda S Diaz-Vegas Alexis A Carr Austin V AV Van Gerwen Julian J Needham Elise J EJ Jevon Dillon D Chen Sing-Young SY Hoehn Kyle L KL Brandon Amanda E AE Macia Laurance L Cooney Gregory J GJ Shortreed Michael R MR Smith Lloyd M LM Keller Mark P MP Thorn Peter P Larance Mark M James David E DE Humphrey Sean J SJ Kebede Melkam A MA

iScience 20210909 10

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 ma ...[more]

PMID: 34622154

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Project description:BackgroundPancreatic Islets of Langerhans are heterogeneous tissues consisting of multiple endocrine cell types that carry out distinct yet coordinated roles to regulate blood glucose homeostasis. Islet dysfunction and specifically failure of the beta cells to secrete adequate insulin are known precursors to type 2 diabetes (T2D) onset. However, the exact genetic, (epi)genomic, and environmental mechanisms that contribute to islet failure, and ultimately to T2D pathogenesis, require further elucidation.Scope of reviewThis review summarizes efforts and advances in dissection of the complex genetic underpinnings of islet function and resilience in T2D pathogenesis. In this review, we will highlight results of the latest T2D genome-wide association study (GWAS) and discuss how these data are being combined with clinical measures in patients to uncover putative T2D subtypes and with functional (epi)genomic studies in islets to understand the genetic programming of islet cell identity, function, and adaptation. Finally, we discuss new and important opportunities to address major knowledge gaps in our understanding of islet (dys)function in T2D risk and progression.Major conclusionsGenetic variation exerts clear effects on the islet epigenome, regulatory element usage, and gene expression. Future (epi)genomic comparative analyses between T2D and normal islets should incorporate genetics to distinguish patient-specific from disease-specific differences. Incorporating genotype information into future analyses and studies will also enable more precise insights into the molecular genetics of islet deficiency and failure in T2D risk, and should ultimately contribute to a stratified view of T2D and more precise treatment strategies. Islet cellular heterogeneity continues to remain a challenge for understanding the associations between islet failure and T2D development. Further efforts to obtain purified islet cell type populations and determine the specific genetic and environmental effects on each will help address this. Beyond observation of islets at steady state conditions, more research of islet stress and stimulation responses are needed to understand the transition of these tissues from a healthy to diseased state. Together, focusing on these objectives will provide more opportunities to prevent, treat, and manage T2D.

Dataset Information

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

Publications

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

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