Role of DPP IV Inhibitors Beyond Diabetes

Abstract

Dipeptidyl Peptidase-IV (DPP IV) is a protease enzyme belonging to S9B subfamily of serine protease enzyme family, known well as T cell activation antigen CD26 and getting expressed in multiple cells - majorly exocrine gland cells, absorptive epithelia and activated leukocytes and functions both enzymatically and non enzymatically. DPP-IV enzyme has emerged as a pharmacological target, first to newlinewhich is diabetes where inhibition of DPP-IV by synthetic molecules Gliptins and natural origin constituents, increases level of incretin hormone GLP-1 and leads to regulation of blood sugar level providing anti-diabetic effect. The widespread expression of DPP-IV enzyme in tissues such as the vascular, renal , pulmonary, intestinal, neural, immune cells and many more suggests its role in multiple physiological function and pathogenesis of diseased condition anchoring one particular key mechanism or different and multiple mechanisms at molecular level. Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Anti-oxidants, antihyper-glycemics and insulin sensitizing agents are reported to reduce cognitive dysfunction in diabetes preventing neurodegenration. DPP-IV inhibitors act as anti-oxidant by reducing production of free radical generation. This DPP-4 enzyme inhibition increase serum level of GLP-1 level which also has neuroprotective and memory enhancing action. On the basis of the evidences the present study was carried out to evaluate effect of Sitagliptin (10 and 20mg/kg, P.O.) and Saxagliptin (0.5 and 1 mg/kg, P.O.) in streptozotocin (120mg/kg body weight, single dose, i.p.) induced neurodegenerative mice performing neuropharmacological behavioural tests and estimation of brain neurotransmitter level.