Receptor bombesina subtipo 3 (brs-3)Diana terapéutica en la obesidad y en la diabetes

Abstract

Morbid obesity is a chronic disease characterized by excessive accumulation of fat, which is frequently associated to low glucose tolerance and insulin resistance in muscle tissue, as well as to hyperinsulinism in fasting and postprandial state, degenerating, in a variable period of time depending upon the patient, in a type 2 diabetes. Several studies have shown that a disruption of the Bombesin Receptor Subtype-3 ¿a membrane protein of unknown natural ligand, that is to say, an orphan receptor¿ could be the origin of metabolic alterations such as obesity. Furthermore, the skeletal muscle, which expresses the BRS-3 receptor, is a key factor in its sugar metabolism, making the muscle a suitable tissue for the analysis of its role in the human glucose metabolism. The results of this study, performed in human skeletal muscle, show that the BRS-3 receptor is expressed in normal subjects, to a lower than normal extent in obese, and also, although in an even lower degree, in type 2 diabetic patients. In addition, BRS-3-AP, stimulates the expression of BRS-3 and glucotransporter 4, the protein kinases activity, the glucose transport, glycogen synthase a activity and glycogen synthesis. Finally, the cells from obese patients, and particularly those from type 2 diabetics, seem to be more sensitive to this analogue than those from normal subjects, In conclusion, the results of this study demonstrate the implication of the BRS-3 receptor in obesity and diabetes syndromes. The BRS-3 receptor and/or its agonist peptide could be used as a molecular target in the therapy of obesity and diabetes.