Unraveling pancreatic islet biology by quantitative proteomics

Zhou, Jian; Dann, Geoffrey P.; Liew, Chong Wee; Smith, Richard D.; Kulkarni, Rohit; Qian, Weijun

doi:10.1586/epr.11.39

Cited by 14 publications

(24 citation statements)

References 84 publications

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“…With the rapid development of mass spectrometry (MS) technology, previous large-scale efforts have helped to define the islet proteome and revealed its variability across chronic high glucose treatment, or during the development of diabetes or fat (2,3). These works have advanced our understanding of basic islet biology and catalyzed the discovery of proteins involved in islet dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Phosphoproteomics Revealed Glucose-Stimulated Responses of Islet Associated with Insulin Secretion

Tang

et al. 2015

J. Proteome Res.

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As central tissue of glucose homeostasis, islet has been an important focus of diabetes research. Phosphorylation plays pivotal roles in islet function, especially in islet glucose-stimulated insulin secretion. A systematic view on how phosphorylation networks were coordinately regulated in this process remains lacking, partially due to the limited amount of islets from an individual for a phosphoproteomic analysis. Here we optimized the in-tip and best-ratio phosphopeptide enrichment strategy and a SILAC-based workflow for processing rat islet samples. With limited islet lysates from each individual rat (20-47 μg), we identified 8539 phosphosites on 2487 proteins. Subsequent quantitative analyses uncovered that short-term (30 min) high glucose stimulation induced coordinate responses of islet phosphoproteome on multiple biological levels, including insulin secretion related pathways, cytoskeleton dynamics, protein processing in ER and Golgi, transcription and translation, and so on. Furthermore, three glucose-responsive phosphosites (Prkar1a pT75pS77 and Tagln2 pS163) from the data set were proved to be correlated with insulin secretion. Overall, we initially gave an in-depth map of islet phosphoproteome regulated by glucose on individual rat level. This was a significant addition to our knowledge about how phosphorylation networks responded in insulin secretion. Also, the list of changed phosphosites was a valuable resource for molecular researchers in diabetes field.

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Section: Introductionmentioning

confidence: 99%

Quantitative Phosphoproteomics Revealed Glucose-Stimulated Responses of Islet Associated with Insulin Secretion

Tang

et al. 2015

J. Proteome Res.

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“…The pancreatic islets constitute 1-2% of the total cell mass of an adult pancreas [65]. The coding genes and proteins expressed in the pancreas are described and characterized in various publications [66]. However, to the best of our knowledge, a reference list from a free-labeled MS approach analyzing the subset of proteins secreted by the islets or β-cells is not yet available.…”

Section: Discussionmentioning

confidence: 99%

In silico approach to predict pancreatic β-cells classically secreted proteins

et al. 2020

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Pancreatic β-cells, residents of the islets of Langerhans, are the unique insulin-producers in the body. Their physiology is a topic of intensive studies aiming to understand the biology of insulin production and its role in diabetes pathology. However, investigations about these cells’ subset of secreted proteins, the secretome, are surprisingly scarce and a list describing islet/β-cell secretome upon glucose-stimulation is not yet available. In silico predictions of secretomes are an interesting approach that can be employed to forecast proteins likely to be secreted. In this context, using the rationale behind classical secretion of proteins through the secretory pathway, a Python tool capable of predicting classically secreted proteins was developed. This tool was applied to different available proteomic data (human and rodent islets, isolated β-cells, β-cell secretory granules, and β-cells supernatant), filtering them in order to selectively list only classically secreted proteins. The method presented here can retrieve, organize, search and filter proteomic lists using UniProtKB as a central database. It provides analysis by overlaying different sets of information, filtering out potential contaminants and clustering the identified proteins into functional groups. A range of 70–92% of the original proteomes analyzed was reduced generating predicted secretomes. Islet and β-cell signal peptide-containing proteins, and endoplasmic reticulum-resident proteins were identified and quantified. From the predicted secretomes, exemplary conservational patterns were inferred, as well as the signaling pathways enriched within them. Such a technique proves to be an effective approach to reduce the horizon of plausible targets for drug development or biomarkers identification.

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“…The strength of our study resides in the use of label-free proteome quantification in combination with a careful normalization strategy, to allow a direct exploration of (dis)similarities in protein abundance between human and rat beta cells. As recently reviewed [ 24 ], both descriptive and quantitative proteomic techniques have been used to identify beta cell-selective markers, to characterize the beta cell's adaptation to diabetogenic stress conditions or physiological stimuli, and to characterize the beta cell's secretome [ 25 ]. Data independent alternate-scanning LC-MS/MS achieves reasonably accurate quantification, based on the observation that the average MS signal response for the three most intense tryptic peptides per mole of protein is constant within a coefficient of variation of less than +/−10% [ 14 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

Species-Related Differences in the Proteome of Rat and Human Pancreatic Beta Cells

Martens

2015

Journal of Diabetes Research

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The core proteomes of human and rat pancreatic beta cells were compared by label-free LC-MS/MS: this resulted in quantification of relative molar abundances of 707 proteins belonging to functional pathways of intermediary metabolism, protein synthesis, and cytoskeleton. Relative molar abundances were conserved both within and between pathways enabling the selection of a housekeeping network for geometric normalization and the analysis of potentially relevant differential expressions. Human beta cells differed from rat beta cells in their lower level of enzymes involved in glucose sensing (MDH1, PC, and ACLY) and upregulation of lysosomal enzymes. Human cells also expressed more heat shock proteins and radical scavenging systems: apart from SOD2, they expressed high levels of H2O2-scavenger peroxiredoxin 3 (PRDX3), confirmed by microarray, Western blotting, and microscopy. Besides conferring lower susceptibility to oxidative stress to human cells PRDX3 might also play a role in physiological redox regulation as, in rat, its expression was restricted to a beta cell subset with higher metabolic glucose responsiveness. In conclusion, although their core proteomic architecture is conserved, human and rat beta cells differ in their molar expression of key enzymes involved in glucose sensing and redox control.

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Unraveling pancreatic islet biology by quantitative proteomics

Cited by 14 publications

References 84 publications

Quantitative Phosphoproteomics Revealed Glucose-Stimulated Responses of Islet Associated with Insulin Secretion

Quantitative Phosphoproteomics Revealed Glucose-Stimulated Responses of Islet Associated with Insulin Secretion

In silico approach to predict pancreatic β-cells classically secreted proteins

Species-Related Differences in the Proteome of Rat and Human Pancreatic Beta Cells

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