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Erik Renström

Erik Renström

Vice-chancellor

Erik Renström

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 of Diabetes Research in Sweden
  • 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)
  • Neuroendocrine Cell Biology
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 0303-7207