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Anna Edlund

Affiliated researcher

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Endogenous beta-cell CART regulates insulin secretion and transcription of beta-cell genes

Author

  • L Shcherbina
  • A Edlund
  • J L S Esguerra
  • M Abels
  • Y Zhou
  • E Ottosson-Laakso
  • C B Wollheim
  • O Hansson
  • L Eliasson
  • N Wierup

Summary, in English

Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing. In addition, CART silencing reduced the expression of a network of transcription factors essential for beta-cell function. Moreover, in RNAseq data from human islet donors, CARTPT expression levels correlated with insulin, exocytosis genes and key beta-cell transcription factors. Thus, endogenous beta-cell CART regulates insulin expression and secretion in INS-1 (832/13) cells, via actions on the exocytotic machinery and a network of beta-cell transcription factors. We conclude that CART is important for maintaining the beta-cell phenotype.

Department/s

  • Neuroendocrine Cell Biology
  • Diabetes - Islet Cell Exocytosis
  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2017-02-24

Language

English

Pages

52-60

Publication/Series

Molecular and Cellular Endocrinology

Volume

447

Document type

Journal article

Publisher

Elsevier

Topic

  • Cell and Molecular Biology

Keywords

  • Journal Article

Status

Published

Research group

  • Neuroendocrine Cell Biology
  • Diabetes - Islet Cell Exocytosis
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1872-8057