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Search: (WFRF:(Smith Eric A.)) srt2:(2020-2021) > (2021) > Proteomic profiling...

  • Ngo, DebbyBeth Israel Deaconess Medical Center (author)

Proteomic profiling reveals novel biomarkers and pathways in yype 2 diabetes risk

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-03-08
  • American Society for Clinical Investigation,2021

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:385d32da-20ab-4362-8a8f-8b4e4ddbfa08
  • https://lup.lub.lu.se/record/385d32da-20ab-4362-8a8f-8b4e4ddbfa08URI
  • https://doi.org/10.1172/jci.insight.144392DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Recent advances in proteomic technologies have made high throughput profiling of low abundance proteins in large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based proteomic profiling could identify biomarkers associated with future development of type 2 diabetes (T2DM) beyond known risk factors. We identified dozens of markers with highly significant associations with future T2DM across two large longitudinal cohorts (n=2,839) followed for up to 16 years. We leveraged proteomic, metabolomic, genetic and clinical data from humans to nominate one specific candidate to test for potential causal relationships in model systems. Our studies identified functional effects of aminoacylase 1 (ACY1), a top protein association with future T2DM risk, on amino acid metabolism and insulin homeostasis in vitro and in vivo. Further, a loss-of-function variant associated with circulating levels of the biomarker WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 (WFIKKN2) was in turn associated with fasting glucose, hemoglobin A1c and HOMA-IR measurements in humans. In addition to identifying novel disease markers and potential pathways in T2DM, we provide publicly available data to be leveraged for new insights about gene function and disease pathogenesis in the context of human metabolism. .

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Benson, Mark DBeth Israel Deaconess Medical Center (author)
  • Long, Jonathan ZStanford University (author)
  • Chen, Zsu-ZsuBeth Israel Deaconess Medical Center (author)
  • Wang, RuiqiBoston University (author)
  • Nath, Anjali KBeth Israel Deaconess Medical Center (author)
  • Keyes, Michelle JBeth Israel Deaconess Medical Center (author)
  • Shen, DongxiaoBeth Israel Deaconess Medical Center (author)
  • Sinha, SumitaBeth Israel Deaconess Medical Center (author)
  • Kuhn, EricBroad Institute (author)
  • Morningstar, Jordan EBeth Israel Deaconess Medical Center (author)
  • Shi, XuBeth Israel Deaconess Medical Center (author)
  • Peterson, Bennet DBeth Israel Deaconess Medical Center (author)
  • Chan, ChristopherBeth Israel Deaconess Medical Center (author)
  • Katz, Daniel HBeth Israel Deaconess Medical Center (author)
  • Tahir, Usman ABeth Israel Deaconess Medical Center (author)
  • Farrell, Laurie ABeth Israel Deaconess Medical Center (author)
  • Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-ome (author)
  • Mosley, Jonathan DVanderbilt University Medical Center (author)
  • Carr, Steven ABroad Institute (author)
  • Vasan, Ramachandran SNational Heart Lung and Blood Institute,Boston University (author)
  • Larson, Martin GNational Heart Lung and Blood Institute,Boston University (author)
  • Smith, J GustavLund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Heart Failure and Mechanical Support,Forskargrupper vid Lunds universitet,Molecular Epidemiology and Cardiology,Cardiovascular Epigenetics,WCMM- Wallenberg center för molekylär medicinsk forskning,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Sahlgrenska University Hospital(Swepub:lu)med-gvs (author)
  • Wang, Thomas JUniversity of Texas Southwestern Medical Center (author)
  • Yang, QiongBeth Israel Deaconess Medical Center (author)
  • Gerszten, Robert EBroad Institute,Beth Israel Deaconess Medical Center (author)
  • Beth Israel Deaconess Medical CenterStanford University (creator_code:org_t)

Related titles

  • In:JCI Insight: American Society for Clinical Investigation6:52379-3708

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