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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
  • University of Geneva
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • Journal Article
Original languageEnglish
Pages (from-to)52-60
JournalMolecular and Cellular Endocrinology
Volume447
Early online date2017 Feb 24
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes

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