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Search: L773:0012 186X OR L773:1432 0428 > (2015-2019) > CART is overexpress...

  • Abels, MiaLund University,Lunds universitet,Diabetes,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital (author)

CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-06-23
  • Springer Science and Business Media LLC,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-303027
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-303027URI
  • https://doi.org/10.1007/s00125-016-4020-6DOI
  • https://lup.lub.lu.se/record/9aa0a0ed-e63e-4197-9edc-0dff545938aeURI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Aims/hypothesis Insufficient insulin release and hyperglucagonaemia are culprits in type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART, encoded by Cartpt) affects islet hormone secretion and beta cell survival in vitro in rats, and Cart(-/-) mice have diminished insulin secretion. We aimed to test if CART is differentially regulated in human type 2 diabetic islets and if CART affects insulin and glucagon secretion in vitro in humans and in vivo in mice. Methods CART expression was assessed in human type 2 diabetic and non-diabetic control pancreases and rodent models of diabetes. Insulin and glucagon secretion was examined in isolated islets and in vivo in mice. Ca2+ oscillation patterns and exocytosis were studied in mouse islets. Results We report an important role of CART in human islet function and glucose homeostasis in mice. CART was found to be expressed in human alpha and beta cells and in a subpopulation of mouse beta cells. Notably, CART expression was several fold higher in islets of type 2 diabetic humans and rodents. CART increased insulin secretion in vivo in mice and in human and mouse islets. Furthermore, CART increased beta cell exocytosis, altered the glucose-induced Ca2+ signalling pattern in mouse islets from fast to slow oscillations and improved synchronisation of the oscillations between different islet regions. Finally, CART reduced glucagon secretion in human and mouse islets, as well as in vivo in mice via diminished alpha cell exocytosis. Conclusions/interpretation We conclude that CART is a regulator of glucose homeostasis and could play an important role in the pathophysiology of type 2 diabetes. Based on the ability of CART to increase insulin secretion and reduce glucagon secretion, CART-based agents could be a therapeutic modality in type 2 diabetes.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Riva, MatteoLund University,Lunds universitet,Diabetes,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-mtr (author)
  • Bennet, HedvigLund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-hgb (author)
  • Ahlqvist, EmmaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)infl-eah (author)
  • Dyachok, OlegUppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)olegdyac (author)
  • Nagaraj, ViniLund University,Lunds universitet,Diabetes,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-vng (author)
  • Shcherbina, LiliyaLund University,Lunds universitet,Diabetes,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)med-lsr (author)
  • Fred, Rikard G.Lund University,Lunds universitet,Diabetes,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)med-rkf (author)
  • Poon, WennyLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-wyp (author)
  • Sörhede-Winzell, MariaLund University,Lunds universitet,Diabetes,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)medk-msw (author)
  • Fadista, JoaoLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-jft (author)
  • Lindqvist, AndreasLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)medk-alt (author)
  • Kask, LenaLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)klke-lka (author)
  • Sathanoori, RamasriLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)med-rst (author)
  • Dekker-Nitert, MarloesLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)medk-mad (author)
  • Kuhar, Michael J.Emory Univ, Yerkes Res Ctr, Atlanta, GA 30322 USA.,Emory University (author)
  • Ahrén, BoLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)med-bah (author)
  • Wollheim, Claes B.Univ Med Ctr, Dept Cell Physiol & Metab, Geneva, Switzerland.,University Medical Center, Geneva(Swepub:lu)med-cwe (author)
  • Hansson, OlaLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)medk-oha (author)
  • Tengholm, AndersUppsala University,Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)andeteng (author)
  • Fex, MalinLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)medk-mf0 (author)
  • Renström, ErikLund 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)
  • Groop, LeifLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups(Swepub:lu)endo-lgr (author)
  • Lyssenko, ValeriyaLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Steno Diabetes Center Copenhagen(Swepub:lu)endo-vly (author)
  • Wierup, NilsLund 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)
  • DiabetesForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Diabetologia: Springer Science and Business Media LLC59:9, s. 1928-19370012-186X1432-0428

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