Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/22526606http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22526606http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22526606http://www.w3.org/2000/01/rdf-schema#comment"

Aims/hypothesis

During the development of type 2 diabetes mellitus, beta cells are often exposed to a high glucose/hyperlipidaemic environment, in which the levels of reactive oxygen species (ROS) are elevated. In turn, ROS can trigger an apoptotic response leading to beta cell death, by activating mitogen-activated protein kinase (MAPK) signalling cascades. Here we test the hypothesis that serine/threonine protein phosphatase 5 (PP5) acts to suppress proapoptotic c-Jun N-terminal kinase (JNK) signalling in beta cells.

Methods

Ppp5c(-/-) and Ppp5c(+/+) mice were subjected to intraperitoneal glucose (IPGTT) or insulin tolerance tests. Pancreatic islets from Ppp5c(-/-) and Ppp5c(+/+) mice or MIN6 cells treated with short-interfering RNA targeting PP5 were exposed to palmitate or H(2)O(2) to activate MAPK signalling. Changes in protein phosphorylation, mRNA expression, apoptosis and insulin secretion were detected by western blot analysis, quantitative RT-PCR or ELISA.

Results

Ppp5c(-/-) mice weighed less and exhibited reduced fasting glycaemia and improved glucose tolerance during IPGTT, but retained normal insulin sensitivity and islet volume. Comparison of MAPK signalling in islets from Ppp5c(-/-) mice and MIN6 cells revealed that the lack of PP5 was associated with enhanced H(2)O(2)-induced phosphorylation of JNK and c-Jun. Cells with reduced PP5 also showed enhanced JNK phosphorylation and apoptosis after palmitate treatment. PP5 suppression in MIN6 cells correlated with hypersecretion of insulin in response to glucose.

Conclusions/interpretation

PP5 deficiency in mice is associated with reduced weight gain, lower fasting glycaemia, and improved glucose tolerance during IPGTT. At a molecular level, PP5 helps suppress apoptosis in beta cells by a mechanism that involves regulation of JNK phosphorylation."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.org/dc/terms/identifier"doi:10.1007/s00125-012-2541-1"xsd:string
http://purl.uniprot.org/citations/22526606http://purl.org/dc/terms/identifier"doi:10.1007/s00125-012-2541-1"xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/author"Sjoeholm A."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/author"Sjoeholm A."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/author"Honkanen R.E."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/author"Honkanen R.E."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/author"Amable L."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/author"Amable L."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/author"Grankvist N."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/author"Grankvist N."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/author"Ortsaeter H."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/author"Ortsaeter H."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/pages"2005-2015"xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/pages"2005-2015"xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/title"Serine/threonine protein phosphatase 5 regulates glucose homeostasis in vivo and apoptosis signalling in mouse pancreatic islets and clonal MIN6 cells."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/title"Serine/threonine protein phosphatase 5 regulates glucose homeostasis in vivo and apoptosis signalling in mouse pancreatic islets and clonal MIN6 cells."xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/volume"55"xsd:string
http://purl.uniprot.org/citations/22526606http://purl.uniprot.org/core/volume"55"xsd:string
▶