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Activation of leptin and insulin pathways in non diabetic IRS2 knockout

AuthorsGonzález-Rodríguez, Águeda; Valverde, Ángela M.; Barrios, Vicente
Issue Date2010
Citation49th Annual Meeting of the European Society for Pediatric Endocrinology (2010)
Abstract[Background]: Insulin resistance and type 2 diabetes correlates with impaired leptin and insulin signaling. The use of IRS2 “knockout” (IRS2-/-) mice allows exploring signaling targets for both hormones and the relationship with alterations of glucose homeostasis and diabetes. [Objective and hypotheses]: Our aims were to analyze in IRS2-/- mice leptin and insulin pathways and the relation with development of diabetes. [Methods]: Twenty four mice with an age between 10 and 12 weeks were studied, 8 controls (C), 8 diabetic IRS2-/- (D) (blood glucose >400 mg/dl) and 8 non diabetic mice IRS2-/- (blood glucose <200 mg/dl) (ND). Diabetic mice were sacrificed 24 hours after blood glucose increase. In all animals halves of hypothalami were homogenized to analyze Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and Akt activation, long form of leptin receptor (ObRb), suppressor of cytokine signaling 3 (SOCS3), Foxo1 and IRS1 levels by Western blot, as well as the association of regulatory subunit of phosphatidylinositol 3-kinase (PI3K) with IRS1 by immunoprecipitation. The other half of hypothalamus was used to determine relative levels of neuropeptide Y (NPY) and proopiomelanocortin by real time PCR. [Results]: Leptin and insulin serum levels were increased in ND, compared to C and D (p<0.01), as well JAK2 and STAT3 activation (p<0.05) without changes in ObRb. IRS1 levels and association with p85 and Akt activation were augmented in ND (p<0.05). The increase of Foxo 1 is related to an increase of NPY messenger ARN (p<0.05) and a reduction of proopiomelanocortin messenger ARN (p<0.05) in D mice. [Conclusions]: In conclusion, activation of leptin and insulin signaling pathways together with the differential pattern of neuropeptides involved in food intake and energy homeostasis suggest that these targets could be of interest in the treatment of insulin resistance and type 2 diabetes.
DescriptionResumen del póster presentado al 49th Annual Meeting of the European Society for Pediatric Endocrinology (ESPE), celebrado en Praga (Republica Checa) del 22 al 25 de septiembre de 2010.-- et al.
Appears in Collections:(IIBM) Comunicaciones congresos
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