Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy

    1. Berthold Hocher1,3,4
    1. 1Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
    2. 2Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
    3. 3Institut für Laboriatorumsmedizin IFLb, Berlin, Germany
    4. 4Departments of Embryology and Nephrology, Basic Medical College, Jinan University, Guangzhou, China
    1. Correspondence should be addressed to B Hocher; Email: hocher{at}


    Diabetic nephropathy is one of the most frequent, devastating and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membrane-bound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure- and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations.

    • Received 17 March 2017
    • Accepted 18 April 2017
    • Made available online as an Accepted Preprint 18 April 2017
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