Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Andreas Lindqvist

Andreas Lindqvist

Research engineer

Andreas Lindqvist

Intestinal CART is a regulator of GIP and GLP-1 secretion and expression

Author

  • L. Shcherbina
  • A. Lindqvist
  • A. H. Thorén Fischer
  • E. Ahlqvist
  • E. Zhang
  • S. E. Falkmer
  • E. Renström
  • J. Koffert
  • H. Honka
  • N. Wierup

Summary, in English

Impaired incretin effect is a culprit in Type 2 Diabetes. Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide controlling pancreatic islet hormone secretion and beta-cell survival. Here we studied the potential expression of CART in enteroendocrine cells and examined the role of CART as a regulator of incretin secretion and expression. CART expression was found in glucose-dependent insulinotropic polypeptide (GIP)-producing K-cells and glucagon-like peptide-1 (GLP-1)-producing L-cells in human duodenum and jejunum and circulating CART levels were increased 60 min after a meal in humans. CART expression was increased by fatty acids and GIP, but unaffected by glucose in GLUTag and STC-1 cells. Exogenous CART had no effect on GIP and GLP-1 expression and secretion in GLUTag or STC-1 cells, but siRNA-mediated silencing of CART reduced GLP-1 expression and secretion. Furthermore, acute intravenous administration of CART increased GIP and GLP-1 secretion during an oral glucose-tolerance test in mice. We conclude that CART is a novel constituent of human K- and L-cells with stimulatory actions on incretin secretion and that interfering with the CART system may be a therapeutic avenue for T2D.

Department/s

  • EXODIAB: Excellence in Diabetes Research in Sweden
  • LUDC (Lund University Diabetes Centre)-lup-obsolete
  • Neuroendocrine Cell Biology
  • Genomics, Diabetes and Endocrinology

Publishing year

2018-04-06

Language

English

Pages

8-16

Publication/Series

Molecular and Cellular Endocrinology

Volume

476

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • CART
  • Cocaine- and amphetamine-regulated transcript
  • Enteroendocrine cells
  • GIP
  • GLP-1
  • Incretin hormones

Status

Published

Research group

  • LUDC (Lund University Diabetes Centre)-lup-obsolete
  • Neuroendocrine Cell Biology
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 0303-7207