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Endogenous beta-cell CART regulates insulin secretion and transcription of beta-cell genes

Shcherbina, L LU ; Edlund, A LU ; Esguerra, J L S LU ; Abels, M LU ; Zhou, Y LU ; Ottosson-Laakso, E LU ; Wollheim, C B LU ; Hansson, O LU ; Eliasson, L LU and Wierup, N LU (2017) In Molecular and Cellular Endocrinology
Abstract

Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing. In addition, CART silencing reduced the expression of a network of transcription factors essential for beta-cell function. Moreover, in RNAseq data from human islet donors, CARTPT expression... (More)

Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing. In addition, CART silencing reduced the expression of a network of transcription factors essential for beta-cell function. Moreover, in RNAseq data from human islet donors, CARTPT expression levels correlated with insulin, exocytosis genes and key beta-cell transcription factors. Thus, endogenous beta-cell CART regulates insulin expression and secretion in INS-1 (832/13) cells, via actions on the exocytotic machinery and a network of beta-cell transcription factors. We conclude that CART is important for maintaining the beta-cell phenotype.

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publication status
epub
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Journal Article
in
Molecular and Cellular Endocrinology
publisher
Elsevier
external identifiers
  • scopus:85014058608
  • wos:000400719300006
ISSN
1872-8057
DOI
10.1016/j.mce.2017.02.027
language
English
LU publication?
yes
id
8907b254-12ae-4efc-a9f8-98cf27f21d34
date added to LUP
2017-03-22 10:55:51
date last changed
2017-09-18 11:33:39
@article{8907b254-12ae-4efc-a9f8-98cf27f21d34,
  abstract     = {<p>Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing. In addition, CART silencing reduced the expression of a network of transcription factors essential for beta-cell function. Moreover, in RNAseq data from human islet donors, CARTPT expression levels correlated with insulin, exocytosis genes and key beta-cell transcription factors. Thus, endogenous beta-cell CART regulates insulin expression and secretion in INS-1 (832/13) cells, via actions on the exocytotic machinery and a network of beta-cell transcription factors. We conclude that CART is important for maintaining the beta-cell phenotype.</p>},
  author       = {Shcherbina, L and Edlund, A and Esguerra, J L S and Abels, M and Zhou, Y and Ottosson-Laakso, E and Wollheim, C B and Hansson, O and Eliasson, L and Wierup, N},
  issn         = {1872-8057},
  keyword      = {Journal Article},
  language     = {eng},
  month        = {02},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Endocrinology},
  title        = {Endogenous beta-cell CART regulates insulin secretion and transcription of beta-cell genes},
  url          = {http://dx.doi.org/10.1016/j.mce.2017.02.027},
  year         = {2017},
}