The CaMK4/CREB/IRS-2 cascade stimulates proliferation and inhibits apoptosis of β-cells.

Progressive reduction in β-cell mass is responsible for the development of type 2 diabetes mellitus, and alteration in insulin receptor substrate 2 (IRS-2) abundance plays a critical role in this process. IRS-2 expression is stimulated by the transcription factor cAMP response element-binding protei...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bo Liu, Helena Barbosa-Sampaio, Peter M Jones, Shanta J Persaud, Dany S Muller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f3c3c4ba8adc426c98d895b3aef45dbf
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f3c3c4ba8adc426c98d895b3aef45dbf
record_format	dspace
spelling	oai:doaj.org-article:f3c3c4ba8adc426c98d895b3aef45dbf2021-11-18T08:14:10ZThe CaMK4/CREB/IRS-2 cascade stimulates proliferation and inhibits apoptosis of β-cells.1932-620310.1371/journal.pone.0045711https://doaj.org/article/f3c3c4ba8adc426c98d895b3aef45dbf2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23049845/?tool=EBIhttps://doaj.org/toc/1932-6203Progressive reduction in β-cell mass is responsible for the development of type 2 diabetes mellitus, and alteration in insulin receptor substrate 2 (IRS-2) abundance plays a critical role in this process. IRS-2 expression is stimulated by the transcription factor cAMP response element-binding protein (CREB) and we recently demonstrated that Ca(2+)/calmodulin dependent kinase 4 (CaMK4) is upstream of CREB activation in β-cells. This study investigated whether CaMK4 is also a potential target to increase β-cell mass through CREB-mediated IRS-2 expression, by quantifying mouse MIN6 β-cell proliferation and apoptosis following IRS-2 knockdown, CaMKs inhibition and alterations in CaMK4 and CREB expression. Expression of constitutively active CaMK4 (ΔCaMK4) and CREB (CREB(DIEDLM)) significantly stimulated β-cell proliferation and survival. In contrast, expression of their corresponding dominant negative forms (Δ(K75E)CaMK4 and CREB(M1)) and silencing of IRS-2 increased apoptosis and reduced β-cell division. Moreover, CREB(DIEDLM) and CREB(M1) expression completely abolished the effects of Δ(K75E)CaMK4 and of ΔCaMK4, respectively. Our results indicate that CaMK4 regulates β-cell proliferation and apoptosis in a CREB-dependent manner and that CaMK4-induced IRS-2 expression is important in these processes.Bo LiuHelena Barbosa-SampaioPeter M JonesShanta J PersaudDany S MullerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45711 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bo Liu Helena Barbosa-Sampaio Peter M Jones Shanta J Persaud Dany S Muller The CaMK4/CREB/IRS-2 cascade stimulates proliferation and inhibits apoptosis of β-cells.
description	Progressive reduction in β-cell mass is responsible for the development of type 2 diabetes mellitus, and alteration in insulin receptor substrate 2 (IRS-2) abundance plays a critical role in this process. IRS-2 expression is stimulated by the transcription factor cAMP response element-binding protein (CREB) and we recently demonstrated that Ca(2+)/calmodulin dependent kinase 4 (CaMK4) is upstream of CREB activation in β-cells. This study investigated whether CaMK4 is also a potential target to increase β-cell mass through CREB-mediated IRS-2 expression, by quantifying mouse MIN6 β-cell proliferation and apoptosis following IRS-2 knockdown, CaMKs inhibition and alterations in CaMK4 and CREB expression. Expression of constitutively active CaMK4 (ΔCaMK4) and CREB (CREB(DIEDLM)) significantly stimulated β-cell proliferation and survival. In contrast, expression of their corresponding dominant negative forms (Δ(K75E)CaMK4 and CREB(M1)) and silencing of IRS-2 increased apoptosis and reduced β-cell division. Moreover, CREB(DIEDLM) and CREB(M1) expression completely abolished the effects of Δ(K75E)CaMK4 and of ΔCaMK4, respectively. Our results indicate that CaMK4 regulates β-cell proliferation and apoptosis in a CREB-dependent manner and that CaMK4-induced IRS-2 expression is important in these processes.
format	article
author	Bo Liu Helena Barbosa-Sampaio Peter M Jones Shanta J Persaud Dany S Muller
author_facet	Bo Liu Helena Barbosa-Sampaio Peter M Jones Shanta J Persaud Dany S Muller
author_sort	Bo Liu
title	The CaMK4/CREB/IRS-2 cascade stimulates proliferation and inhibits apoptosis of β-cells.
title_short	The CaMK4/CREB/IRS-2 cascade stimulates proliferation and inhibits apoptosis of β-cells.
title_full	The CaMK4/CREB/IRS-2 cascade stimulates proliferation and inhibits apoptosis of β-cells.
title_fullStr	The CaMK4/CREB/IRS-2 cascade stimulates proliferation and inhibits apoptosis of β-cells.
title_full_unstemmed	The CaMK4/CREB/IRS-2 cascade stimulates proliferation and inhibits apoptosis of β-cells.
title_sort	camk4/creb/irs-2 cascade stimulates proliferation and inhibits apoptosis of β-cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f3c3c4ba8adc426c98d895b3aef45dbf
work_keys_str_mv	AT boliu thecamk4crebirs2cascadestimulatesproliferationandinhibitsapoptosisofbcells AT helenabarbosasampaio thecamk4crebirs2cascadestimulatesproliferationandinhibitsapoptosisofbcells AT petermjones thecamk4crebirs2cascadestimulatesproliferationandinhibitsapoptosisofbcells AT shantajpersaud thecamk4crebirs2cascadestimulatesproliferationandinhibitsapoptosisofbcells AT danysmuller thecamk4crebirs2cascadestimulatesproliferationandinhibitsapoptosisofbcells AT boliu camk4crebirs2cascadestimulatesproliferationandinhibitsapoptosisofbcells AT helenabarbosasampaio camk4crebirs2cascadestimulatesproliferationandinhibitsapoptosisofbcells AT petermjones camk4crebirs2cascadestimulatesproliferationandinhibitsapoptosisofbcells AT shantajpersaud camk4crebirs2cascadestimulatesproliferationandinhibitsapoptosisofbcells AT danysmuller camk4crebirs2cascadestimulatesproliferationandinhibitsapoptosisofbcells
_version_	1718422082688122880

The CaMK4/CREB/IRS-2 cascade stimulates proliferation and inhibits apoptosis of β-cells.

Ejemplares similares