DSpace Repository

Ras-GRF1 signaling is required for normal β-cell development and glucose homeostasis

Show simple item record

dc.creator Font de Mora, Jaime
dc.creator Esteban, Luis Miguel
dc.creator Burks, Deborah J.
dc.creator Núñez, Alejandro
dc.creator Garcés, Carmen
dc.creator García-Barrado, María José
dc.creator Iglesias-Osma, María Carmen
dc.creator Moratinos, Julio
dc.creator Santos de Dios, Eugenio
dc.date 2008-06-17T11:26:30Z
dc.date 2008-06-17T11:26:30Z
dc.date 2003-06
dc.date.accessioned 2017-01-31T01:42:39Z
dc.date.available 2017-01-31T01:42:39Z
dc.identifier EMBO J. 2003 June 16; 22(12): 3039–3049
dc.identifier 1460-2075
dc.identifier http://hdl.handle.net/10261/5139
dc.identifier 10.1093/emboj/cdg280
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5139
dc.description Final full-text version of the paper available at: http://www.nature.com/emboj/journal/v22/n12/index.html
dc.description Development of diabetes generally reflects an inadequate mass of insulin-producing β-cells. β-cell proliferation and differentiation are regulated by a variety of growth factors and hormones, including insulin-like growth factor I (IGF-I). GRF1 is a Ras-guanine nucleotide exchange factor known previously for its restricted expression in brain and its role in learning and memory. Here we demonstrate that GRF1 is also expressed in pancreatic islets. Interest ingly, our GRF1-deficient mice exhibit reduced body weight, hypoinsulinemia and glucose intolerance owing to a reduction of β-cells. Whereas insulin resistance is not detected in peripheral tissues, GRF1 knockout mice are leaner due to increased lipid catabolism. The reduction in circulating insulin does not reflect defective glucose sensing or insulin production but results from impaired β-cell proliferation and reduced neogenesis. IGF-I treatment of isolated islets from GRF1 knockouts fails to activate critical downstream signals such as Akt and Erk. The observed phenotype is similar to manifestations of preclinical type 2 diabetes. Thus, our observations demonstrate a novel and specific role for Ras-GRF1 pathways in the development and maintenance of normal β-cell number and function.
dc.description This work was supported by FEDER grants 1FD97-1735 and 1FD97-1678 and CICYT grant SAF00-0069 from MCYT (Spain). J.F.d.M. and D.J.B. were financed by the Ramón y Cajal Program from MCYT (Spain).
dc.description Peer reviewed
dc.format 22195 bytes
dc.format application/pdf
dc.language eng
dc.publisher Nature Publishing Group
dc.rights openAccess
dc.subject Cell growth
dc.subject β-cells
dc.subject Differentiation
dc.subject Differentiation
dc.subject Insulin
dc.subject Ras-GRF1
dc.title Ras-GRF1 signaling is required for normal β-cell development and glucose homeostasis
dc.type Artículo

Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search


My Account