G-PROTEIN COUPLED RECEPTORS- A POTENTIAL NEW DRUG TARGET TO COMBAT DIABETIC SYNDROME: AN OVERVIEWAbstract
G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors (GPLR), comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses. GPCRs are involved in a wide variety of important physiological processes like visual sense, sense of smell, behavioral and mood regulation, regulation of immune system activity and inflammation, autonomic nervous system transmission and cell density sensing. There are two principal signal transduction pathways involving the G protein-linked receptors, cAMP signal pathway and Phosphatidylinositol signal pathway. Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. One of the reasons for the growing public health concern over the rapidly increasing prevalence of obesity in society is its association with the growing incidence of type II diabetes, a combination of conditions often accompanied by increased cardiovascular risk factors. Much effort among health-care providers and pharmaceutical companies is now focused on the discovery of new treatments that alleviate this medical problem. As part of this effort, the G-protein-coupled receptors have recently attracted a lot of attention. GPR119 particularly is of importance because of evidence from in vitro systems and animal models that its modulation may produce favorable effects on glucose homoeostasis, food intake/body weight gain and possibly also β-cell preservation. Many modulators of GPCRs like GPR119, GPR40, GPR41, GPR43 and GPR120 can be used with a great added advantage of improvement in glucose handling and homeostasis in treating diabetes. Relatively high ‘druggability’ of G-protein coupled receptors as compared with many other molecular target classes may provide an insight into the treatment of diabetes. Hence, G protein coupled receptors show a great potential in drug targeting in the process of drug discovery and development. Provided that being clinically well tolerated, these GPCR effectors will prove a boon to the patients suffering from apathy of metabolic syndrome of diabetes.
P. A. Shenoy*, D. D. Bandawane and P. D. Chaudhari
Progressive Education Society’s Modern College of Pharmacy, Sector no. 21, Yamunanagar, Nigdi, Pune-44, Maharashtra, India
22 May, 2011
18 July, 2011
18 September, 2011
01 October, 2011