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

Shcherbina, L.Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups (author)

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.

Lindqvist, A.Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups(Swepub:lu)medk-alt (author)
Thorén Fischer, A. H.Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)medk-aht (author)
Ahlqvist, E.Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)infl-eah (author)
Zhang, E.Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)med-ezg (author)
Falkmer, S. E.Ryhov County Hospital, Jönköping (author)
Renström, E.Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)mphy-ere (author)
Koffert, J.Turku PET Centre (author)
Honka, H.Turku PET Centre (author)
Wierup, N.Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)mphy-nwi (author)
-lup-obsoleteForskargrupper vid Lunds universitet (creator_code:org_t)

By the author/editor: Shcherbina, L.; Lindqvist, A.; Thorén Fischer, ...; Ahlqvist, E.; Zhang, E.; Falkmer, S. E.; show more...; Renström, E.; Koffert, J.; Honka, H.; Wierup, N.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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