Department of Metabolism, Nutrition and Hormones, IIS-Fundación Jiménez Díaz, Madrid, Spain.
Mol Cell Endocrinol. 2013 Mar 10;367(1-2):109-15. doi: 10.1016/j.mce.2012.12.025. Epub 2013 Jan 3.
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.
BRS-3 KO 小鼠出现肥胖和葡萄糖代谢失衡，提示 BRS-3 受体在葡萄糖稳态中发挥重要作用。我们研究了正常、肥胖或 2 型糖尿病（T2D）患者骨骼肌中的 BRS-3 表达情况，以及 [D-Phe(6), β-Ala(11),Phe(13),Nle(14)] 蛙皮素（6-14）-BRS-3 受体激动肽（BRS-3-AP）在沉默 BRS-3 基因前后对葡萄糖相关作用的影响。在代谢改变的肌肉组织和原代培养的肌细胞中，BRS-3 基因/蛋白表达下调。在正常、肥胖和 T2D 细胞中：A）BRS-3-AP 像胰岛素一样增强 BRS-3 和 GLUT-4 mRNA/蛋白水平；促进葡萄糖转运体向质膜转位，B）BRS-3-AP 引起浓度相关的葡萄糖转运刺激，肥胖和 T2D 肌细胞对配体的敏感性高于正常细胞。wortmannin 和 PD98059，但不是 rapamycin，消除了 BRS-3-AP 对葡萄糖转运的刺激作用。BRS-3 在葡萄糖代谢中发挥重要作用，可作为分子靶点，及其配体，用于肥胖和糖尿病的治疗。
