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

Shcherbina, L. LU ; Lindqvist, A. LU ; Thorén Fischer, A. H. LU ; Ahlqvist, E. LU ; Zhang, E. LU ; Falkmer, S. E.; Renström, E. LU ; Koffert, J.; Honka, H. and Wierup, N. LU (2018) In Molecular and Cellular Endocrinology 476. p.8-16
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... (More)

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.

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organization
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Contribution to journal
publication status
published
subject
keywords
CART, Cocaine- and amphetamine-regulated transcript, Enteroendocrine cells, GIP, GLP-1, Incretin hormones
in
Molecular and Cellular Endocrinology
volume
476
pages
8 - 16
publisher
Elsevier
external identifiers
  • scopus:85045472277
ISSN
0303-7207
DOI
10.1016/j.mce.2018.04.002
language
English
LU publication?
yes
id
47d3f4f6-6e79-4fc2-9060-243759e4788e
date added to LUP
2018-04-24 15:34:51
date last changed
2019-03-19 03:53:36
@article{47d3f4f6-6e79-4fc2-9060-243759e4788e,
  abstract     = {<p>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.</p>},
  author       = {Shcherbina, L. and Lindqvist, A. and Thorén Fischer, A. H. and Ahlqvist, E. and Zhang, E. and Falkmer, S. E. and Renström, E. and Koffert, J. and Honka, H. and Wierup, N.},
  issn         = {0303-7207},
  keyword      = {CART,Cocaine- and amphetamine-regulated transcript,Enteroendocrine cells,GIP,GLP-1,Incretin hormones},
  language     = {eng},
  month        = {04},
  pages        = {8--16},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Endocrinology},
  title        = {Intestinal CART is a regulator of GIP and GLP-1 secretion and expression},
  url          = {http://dx.doi.org/10.1016/j.mce.2018.04.002},
  volume       = {476},
  year         = {2018},
}