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Mol Cell Endocrinol. 2018 Nov 15;476:8-16. doi: 10.1016/j.mce.2018.04.002. Epub 2018 Apr 6.

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

Author information

1
Lund University Diabetes Centre, Malmö, Sweden.
2
Department of Clinical Pathology, Ryhov Hospital, Jönköping, Sweden.
3
Turku PET Centre, University of Turku, Turku, Finland.
4
Lund University Diabetes Centre, Malmö, Sweden. Electronic address: nils.wierup@med.lu.se.

Abstract

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.

KEYWORDS:

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

PMID:
29627317
DOI:
10.1016/j.mce.2018.04.002

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