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SCRT1 is a novel beta cell transcription factor with insulin regulatory properties

Chriett, S. LU ; Lindqvist, A. LU ; Shcherbina, L. LU ; Edlund, A. LU ; Abels, M. LU ; Asplund, O. LU ; Martínez López, J. A. ; Ottosson-Laakso, E. LU ; Hatem, G. LU and Prasad, R. B. LU , et al. (2021) In Molecular and Cellular Endocrinology 521.
Abstract

Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the... (More)

Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3β-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Beta cell, INS-1 832/13, Insulin secretion, SCRT1, Type 2 diabetes
in
Molecular and Cellular Endocrinology
volume
521
article number
111107
publisher
Elsevier
external identifiers
  • scopus:85097675778
  • pmid:33309639
ISSN
0303-7207
DOI
10.1016/j.mce.2020.111107
language
English
LU publication?
yes
id
7f3c47b7-4bbb-4c85-ad81-c8c05b7a0cd9
date added to LUP
2020-12-23 22:19:53
date last changed
2021-02-23 04:09:55
@article{7f3c47b7-4bbb-4c85-ad81-c8c05b7a0cd9,
  abstract     = {<p>Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3β-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.</p>},
  author       = {Chriett, S. and Lindqvist, A. and Shcherbina, L. and Edlund, A. and Abels, M. and Asplund, O. and Martínez López, J. A. and Ottosson-Laakso, E. and Hatem, G. and Prasad, R. B. and Groop, L. and Eliasson, L. and Hansson, O. and Wierup, N.},
  issn         = {0303-7207},
  language     = {eng},
  month        = {02},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Endocrinology},
  title        = {SCRT1 is a novel beta cell transcription factor with insulin regulatory properties},
  url          = {http://dx.doi.org/10.1016/j.mce.2020.111107},
  doi          = {10.1016/j.mce.2020.111107},
  volume       = {521},
  year         = {2021},
}