title: Bombesin receptor subtype-3 (BRS-3), a novel candidate as therapeutic molecular target in obesity and diabetes.
abstract: BRS-3 KO-mice developed obesity and unbalanced glucose metabolism, suggesting an important role of BRS-3 receptor in glucose homeostasis. We explored BRS-3 expression in skeletal muscle from normal, obese or type-2 diabetic (T2D) patients, and the effect of [D-Phe(6), β-Ala(11),Phe(13),Nle(14)]bombesin(6-14)-BRS-3-agonist-peptide (BRS-3-AP) - on glucose-related effects, before or after BRS-3 gene silencing. In muscle tissue and primary cultured myocytes from altered metabolic states, BRS-3 gene/protein expressions were down-regulated. In normal, obese and T2D cells: A) BRS-3-AP as insulin enhanced BRS-3 and GLUT-4 mRNA/protein levels; improving glucotransporter translocation to plasma membrane, and B) BRS-3-AP caused a concentration-related-stimulation of glucose transport, being obese and T2D myocytes more sensitive to the ligand than normal. Wortmannin and PD98059, but not rapamycin, abolished the stimulatory action of BRS-3-AP on glucose transport. BRS-3 plays an important role in glucose metabolism, and could be use as a molecular target, and/or its ligand, as a therapeutic agent for obesity and diabetes treatments.
authors.affiliation: Department of Metabolism, Nutrition and Hormones, IIS-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Ramos-Álvarez
authors.forename: Antonio
authors.initials: A
authors.lastname: Martín-Duce
authors.forename: Zaida
authors.initials: Z
authors.lastname: Moreno-Villegas
authors.forename: Raúl
authors.initials: R
authors.lastname: Sanz
authors.forename: César
authors.initials: C
authors.lastname: Aparicio
authors.forename: Sergio
authors.initials: S
authors.lastname: Portal-Núñez
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Mantey
authors.forename: Robert T
authors.initials: RT
authors.lastname: Jensen
authors.forename: Nieves
authors.initials: N
authors.lastname: González
mesh_terms: D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D010455:Peptides / Q000494:pharmacology; D018004:Receptors, Bombesin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D005419:Flavonoids; D051275:Glucose Transporter Type 4; D007328:Insulin; D010455:Peptides; D018004:Receptors, Bombesin; C495692:SLC2A4 protein, human; C107120:bombesin receptor subtype 3; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus; D000077191:Wortmannin