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  • Avall, Karin (author)

Apolipoprotein CIII links islet insulin resistance to beta-cell failure in diabetes

  • Article/chapterEnglish2015

Publisher, publication year, extent ...

  • 2015-05-04
  • Proceedings of the National Academy of Sciences,2015
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-106130
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-106130URI
  • https://doi.org/10.1073/pnas.1423849112DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Insulin resistance and beta-cell failure are the major defects in type 2 diabetes mellitus. However, the molecular mechanisms linking these two defects remain unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only with insulin resistance but also with cardiovascular disorders and inflammation. We now demonstrate that local apoCIII production is connected to pancreatic islet insulin resistance and beta-cell failure. An increase in islet apoCIII causes promotion of a local inflammatory milieu, increased mitochondrial metabolism, deranged regulation of beta-cell cytoplasmic free Ca2+ concentration ([Ca2+](i)) and apoptosis. Decreasing apoCIII in vivo results in improved glucose tolerance, and pancreatic apoCIII knockout islets transplanted into diabetic mice, with high systemic levels of the apolipoprotein, demonstrate a normal [Ca2+](i) response pattern and no hallmarks of inflammation. Hence, under conditions of islet insulin resistance, locally produced apoCIII is an important diabetogenic factor involved in impairment of beta-cell function and may thus constitute a novel target for the treatment of type 2 diabetes mellitus.

Subject headings and genre

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

  • Ali, Yusuf (author)
  • Leibiger, Ingo B. (author)
  • Leibiger, Barbara (author)
  • Moede, Tilo (author)
  • Paschen, Meike (author)
  • Dicker, Andrea (author)
  • Dare, Elisabetta (author)
  • Kohler, Martin (author)
  • Ilegems, Erwin (author)
  • Abdulreda, Midhat H. (author)
  • Graham, Mark (author)
  • Crooke, Rosanne M. (author)
  • Tay, Vanessa S. Y. (author)
  • Refai, Essam (author)
  • Nilsson, Stefan K.Umeå universitet,Fysiologisk kemi(Swepub:umu)nist6501 (author)
  • Jacob, Stefan (author)
  • Selander, Lars (author)
  • Berggren, Per-Olof (author)
  • Juntti-Berggren, Lisa (author)
  • Umeå universitetFysiologisk kemi (creator_code:org_t)

Related titles

  • In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences112:20, s. E2611-E26190027-84241091-6490

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