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Effect of bombesin receptor subtype-3 and its synthetic agonist on signaling, glucose transport and metabolism in myocytes from patients with obesity and type 2 diabetes

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GONZÁLEZ, NIEVES & MARTÍN-DUCE, ANTONIO & MARTÍNEZ-ARRIETA, FÉLIX & Moreno Villegas, Zaida & PORTAL NÚÑEZ, SERGIO & SANZ, RAÚL & EGIDO, JESÚS (2015 ) .Effect of bombesin receptor subtype-3 and its synthetic agonist on signaling, glucose transport and metabolism in myocytes from patients with obesity and type 2 diabetes.

ISO 690

GONZÁLEZ, NIEVES & MARTÍN-DUCE, ANTONIO & MARTÍNEZ-ARRIETA, FÉLIX & Moreno Villegas, Zaida & PORTAL NÚÑEZ, SERGIO & SANZ, RAÚL & EGIDO, JESÚS. 2015 .Effect of bombesin receptor subtype-3 and its synthetic agonist on signaling, glucose transport and metabolism in myocytes from patients with obesity and type 2 diabetes.

https://hdl.handle.net/20.500.12080/39465
dc.contributor.author GONZÁLEZ, NIEVES
dc.contributor.author MARTÍN-DUCE, ANTONIO
dc.contributor.author MARTÍNEZ-ARRIETA, FÉLIX
dc.contributor.author Moreno Villegas, Zaida
dc.contributor.author PORTAL NÚÑEZ, SERGIO
dc.contributor.author SANZ, RAÚL
dc.contributor.author EGIDO, JESÚS
dc.date.accessioned 2024-02-01T18:23:39Z
dc.date.available 2024-02-01T18:23:39Z
dc.date.created 2015
dc.date.issued 2015
dc.identifier.uri https://hdl.handle.net/20.500.12080/39465
dc.description.abstract Bombesin receptor subtype-3 (BRS-3) is an orphan G-protein-coupled receptor (GPCR) member of the bombesin receptor family. Several studies have suggested an association between obesity, alterations in glucose metabolism, diabetes and the BRS-3 receptor. In this study, we focused on patients simultaneously diagnosed with obesity and type 2 diabetes (OB/ T2D). The analysis of BRS-3 expression in the skeletal muscle of these patients revealed a marked decrease in the expression of BRS-3 at the mRNA (23.6±1.3-fold downregulation, p<0.0001) and protein level (49±7% decrease, p<0.05) compared to the normal patients (no obesity and diabetes). Moreover, in cultured primary myocytes from patients with OB/T2D, the synthetic BRS-3 agonist, [D-Try6 ,¿-Ala11,Phe13,Nle14]bombesin6-14, signifi cantly increased the phosphorylation levels of mitogen-activated protein kinase (MAPK), p90RSK1, protein kinase B (PKB) and p70s6K. Specifically, the ligand at 10-11 M induced the maximal phosphorylation of MAPKs (p42, 159±15% of the control; p44, 166±11% of the control; p<0.0001) and p90RSK1 (148±2% of the control, p<0.0001). The basal phosphorylation levels of all kinases were reduced (p<0.05) in the patients with OB/T2D compared to the normal patients. Furthermore, the BRS-3 agonist stimulated glucose transport, which was already detected at 10-12 M (133±9% of the control), reached maximal levels at 10-11 M (160±9%, p<0.0001) and was maintained at up to 10-8 M (overall mean, 153±7%; p<0.007). This effect was less promiment than that attained with 10-8 M insulin (202±9%, p=0.009). The effect of the agonist on glycogen synthase a activity achieved the maximum effect at 10-11 M (165±16% of the control; p<0.0001), which did not differ from that observed with higher concentrations of the agonist. These results suggest that muscle cells isolated from patients with OB/T2D have extremely high sensitivity to the synthetic ligand, and the effects are particularly observed on MAPK and p90RSK1 phosphory lation, as well as glucose uptake. Moreover, our data indicate that BRS-3 may prove to be useful as a potential therapeutic target for the treatment of patients with OB/T2D es_ES
dc.format application/pdf es_ES
dc.language eng es_ES
dc.rights CC-BY es_ES
dc.rights.uri http://creativecommons.org/licenses/by/4.0/deed.es es_ES
dc.title Effect of bombesin receptor subtype-3 and its synthetic agonist on signaling, glucose transport and metabolism in myocytes from patients with obesity and type 2 diabetes es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.rights.accessrights info:eu-repo/semantics/openAccess es_ES
dc.identifier.location N/A es_ES


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