Intestinal CART is a regulator of GIP and GLP-1 secretion and expression
(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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- author
- 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
- organization
- publishing date
- 2018-04-06
- type
- 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
-
- pmid:29627317
- 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
- 2024-10-15 01:29:39
@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}}, keywords = {{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}}, doi = {{10.1016/j.mce.2018.04.002}}, volume = {{476}}, year = {{2018}}, }