Activation of bombesin receptor Subtype-3 by [D-Tyr 6 ,β-Ala 11 ,Phe 13 ,Nle 14 ]bombesin 6-14 increased glucose uptake and lipogenesis in human and rat adipocytes

• Published in: Molecular and cellular endocrinology 2018-10, Vol.474, p.10
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adipocytes - drug effects; Adipocytes - metabolism; Animals; Biological Transport - drug effects; Bombesin - pharmacology; Gene Expression Regulation - drug effects; Glucose - metabolism; Glucose Transporter Type 4 - metabolism; Humans; Insulin - pharmacology; Lipogenesis - drug effects; Male; Phosphorylation - drug effects; Rats, Wistar; Receptors, Bombesin - agonists; Receptors, Bombesin - genetics; Receptors, Bombesin - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 1872-8057
• DOI: 10.1016/j.mce.2018.01.028

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-Tyr ,β-Ala ,Phe ,Nle ]bombesin -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.