File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Pten deletion in RIP-Cre neurons protects against type 2 diabetes by activating the anti-inflammatory reflex

TitlePten deletion in RIP-Cre neurons protects against type 2 diabetes by activating the anti-inflammatory reflex
Authors
Issue Date2014
Citation
Nature Medicine, 2014, v. 20, n. 5, p. 484-492 How to Cite?
Abstract© 2014 Nature America, Inc. All rights reserved. Inflammation has a critical role in the development of insulin resistance. Recent evidence points to a contribution by the central nervous system in the modulation of peripheral inflammation through the anti-inflammatory reflex. However, the importance of this phenomenon remains elusive in type 2 diabetes pathogenesis. Here we show that rat insulin-2 promoter (Rip)-mediated deletion of Pten, a gene encoding a negative regulator of PI3K signaling, led to activation of the cholinergic anti-inflammatory pathway that is mediated by M2 activated macrophages in peripheral tissues. As such, Rip-cre+ Ptenflox/flox mice showed lower systemic inflammation and greater insulin sensitivity under basal conditions compared to littermate controls, which were abolished when the mice were treated with an acetylcholine receptor antagonist or when macrophages were depleted. After feeding with a high-fat diet, the Pten-deleted mice remained markedly insulin sensitive, which correlated with massive subcutaneous fat expansion. They also exhibited more adipogenesis with M2 macrophage infiltration, both of which were abolished after disruption of the anti-inflammatory efferent pathway by left vagotomy. In summary, we show that Pten expression in Rip+ neurons has a critical role in diabetes pathogenesis through mediating the anti-inflammatory reflex.
Persistent Identifierhttp://hdl.handle.net/10722/292972
ISSN
2023 Impact Factor: 58.7
2023 SCImago Journal Rankings: 19.045
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Linyuan-
dc.contributor.authorOpland, Darren-
dc.contributor.authorTsai, Sue-
dc.contributor.authorLuk, Cynthia T.-
dc.contributor.authorSchroer, Stephanie A.-
dc.contributor.authorAllison, Margaret B.-
dc.contributor.authorElia, Andrew J.-
dc.contributor.authorFurlonger, Caren-
dc.contributor.authorSuzuki, Akira-
dc.contributor.authorPaige, Christopher J.-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorWiner, Daniel A.-
dc.contributor.authorMyers, Martin G.-
dc.contributor.authorWoo, Minna-
dc.date.accessioned2020-11-17T14:57:36Z-
dc.date.available2020-11-17T14:57:36Z-
dc.date.issued2014-
dc.identifier.citationNature Medicine, 2014, v. 20, n. 5, p. 484-492-
dc.identifier.issn1078-8956-
dc.identifier.urihttp://hdl.handle.net/10722/292972-
dc.description.abstract© 2014 Nature America, Inc. All rights reserved. Inflammation has a critical role in the development of insulin resistance. Recent evidence points to a contribution by the central nervous system in the modulation of peripheral inflammation through the anti-inflammatory reflex. However, the importance of this phenomenon remains elusive in type 2 diabetes pathogenesis. Here we show that rat insulin-2 promoter (Rip)-mediated deletion of Pten, a gene encoding a negative regulator of PI3K signaling, led to activation of the cholinergic anti-inflammatory pathway that is mediated by M2 activated macrophages in peripheral tissues. As such, Rip-cre+ Ptenflox/flox mice showed lower systemic inflammation and greater insulin sensitivity under basal conditions compared to littermate controls, which were abolished when the mice were treated with an acetylcholine receptor antagonist or when macrophages were depleted. After feeding with a high-fat diet, the Pten-deleted mice remained markedly insulin sensitive, which correlated with massive subcutaneous fat expansion. They also exhibited more adipogenesis with M2 macrophage infiltration, both of which were abolished after disruption of the anti-inflammatory efferent pathway by left vagotomy. In summary, we show that Pten expression in Rip+ neurons has a critical role in diabetes pathogenesis through mediating the anti-inflammatory reflex.-
dc.languageeng-
dc.relation.ispartofNature Medicine-
dc.titlePten deletion in RIP-Cre neurons protects against type 2 diabetes by activating the anti-inflammatory reflex-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/nm.3527-
dc.identifier.pmid24747746-
dc.identifier.scopuseid_2-s2.0-84988227670-
dc.identifier.volume20-
dc.identifier.issue5-
dc.identifier.spage484-
dc.identifier.epage492-
dc.identifier.eissn1546-170X-
dc.identifier.isiWOS:000335710700019-
dc.identifier.issnl1078-8956-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats