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Biomed Res Int. 2015;2015:816164. doi: 10.1155/2015/816164. Epub 2015 Jun 4.

Dipeptidyl Peptidase 4: A New Link between Diabetes Mellitus and Atherosclerosis?

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Postgraduate Program in Clinical and Experimental Physiopathology (FISCLINEX), State University of Rio de Janeiro, 20551-030 Rio de Janeiro, RJ, Brazil ; Diabetes Department, State Institute of Diabetes and Endocrinology (IEDE), 21330-683 Rio de Janeiro, RJ, Brazil.
Metabolism Department, IEDE, Catholic University, 21330-683 Rio de Janeiro, RJ, Brazil.
Obesity Unit, Division of Endocrinology, Department of Internal Medicine, Faculty of Medical Sciences, Policlínica Piquet Carneiro (UERJ), 20551-030 Rio de Janeiro, RJ, Brazil ; Laboratory for Clinical and Experimental Research on Vascular Biology, Biomedical Center, State University of Rio de Janeiro, 20550-013 Rio de Janeiro, RJ, Brazil.


Type 2 diabetes mellitus (T2DM) has become one of the most prevalent noncommunicable diseases in the past years. It is undoubtedly associated with atherosclerosis and increased risk for cardiovascular diseases. Incretins, which are intestinal peptides secreted during digestion, are able to increase insulin secretion and its impaired function and/or secretion is involved in the pathophysiology of T2DM. Dipeptidyl peptidase 4 (DPP4) is an ubiquitous enzyme that regulates incretins and consequently is related to the pathophysiology of T2DM. DPP4 is mainly secreted by endothelial cells and acts as a regulatory protease for cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. In T2DM, the activity of DPP4 seems to be increased and there are a growing number of in vitro and in vivo studies suggesting that this enzyme could be a new link between T2DM and atherosclerosis. Gliptins are a new class of pharmaceutical agents that acts by inhibiting DPP4. Thus, it is expected that gliptin represents a new pharmacological approach not only for reducing glycemic levels in T2DM, but also for the prevention and treatment of atherosclerotic cardiovascular disease in diabetic subjects. We aimed to review the evidences that reinforce the associations between DPP4, atherosclerosis, and T2DM.

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