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Activation of bombesin receptor Subtype-3 by [D-Tyr6,β-Ala11,Phe13,Nle14]bombesin6-14 increased glucose uptake and lipogenesis in human and rat adipocytes

Moreno-Villegas, Zaida, Martín-Duce, Antonio, Aparicio, César, Portal-Núñez, Sergio, Sanz, Raúl, Mantey, Samuel A., Jensen, Robert T., Lorenzo, Oscar, Egido, Jesús, González, Nieves
Molecular and cellular endocrinology 2018 v.474 pp. 10-19
adipocytes, adipose tissue, agonists, animal disease models, bombesin receptors, diabetes, gene expression, genes, glucose, homeostasis, humans, insulin, lipogenesis, mitogen-activated protein kinase, mutation, obesity, patients, protein content, protein synthesis, rats, skeletal muscle, therapeutics
BRS-3 has an important role in glucose homeostasis. Its expression was reduced in skeletal muscle from obese and/or diabetic patients, and BRS-3 KO-mice developed obesity. In this work, focused on rat/human adipose tissue, BRS-3 gene-expression was lower than normal-levels in hyperlipidemic, type-2-diabetic (T2D), and type-1-diabetic rats and also in obese (OB) and T2D patients. Moreover, BRS-3 protein levels were decreased in diabetic rat and in obese and diabetic human fat pieces; but neither mutation nor even polymorphism in the BRS-3-gene was found in OB or T2D patients. Interestingly, in rat and human adipocytes, without metabolic alterations, [D-Tyr⁶,β-Ala¹¹,Phe¹³,Nle¹⁴]bombesin6-14 ―BRS-3-agonist―, as insulin, enhanced BRS-3 gene/protein expression, increased, PKB, p70s6K, MAPKs and p90RSK1 phosphorylation-levels, and induced a concentration-related stimulation of glucose transport, GLUT-4 membrane translocation and lipogenesis, exclusively mediated by BRS-3, and abolished by wortmannin, PD98059 or rapamacyn. These results confirm that BRS-3 and/or its agonist are a potential therapeutic tool for obesity/diabetes.