Bombesin receptor subtype-3 (BRS-3), a novel candidate as therapeutic molecular target in obesity and diabetes
| Autor: | Irene Ramos-Álvarez, Sergio Portal-Núñez, Robert T. Jensen, Raúl Sanz, César Aparicio, Zaida Moreno-Villegas, Samuel A. Mantey, Nieves González, Antonio Martín-Duce |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.medical_treatment Biology Biochemistry Wortmannin chemistry.chemical_compound Mice Endocrinology Internal medicine Diabetes mellitus medicine Myocyte Glucose homeostasis Animals Humans Insulin Molecular Targeted Therapy Obesity Muscle Skeletal Molecular Biology Cells Cultured Aged Flavonoids Mice Knockout Sirolimus Muscle Cells Glucose Transporter Type 4 fungi Glucose transporter Bombesin Biological Transport Middle Aged medicine.disease Androstadienes Receptors Bombesin Glucose chemistry Diabetes Mellitus Type 2 Gene Expression Regulation Bombesin Receptor Subtype-3 Female Peptides |
| Zdroj: | Molecular and cellular endocrinology. 367(1-2) |
| ISSN: | 1872-8057 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect