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J Mol Endocrinol. 2017 Jul;59(1):R1-R10. doi: 10.1530/JME-17-0005. Epub 2017 Apr 18.

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

Hasan AA1,2, Hocher B3,4,5.

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Institute of Nutritional ScienceUniversity of Potsdam, Potsdam, Germany.
Department of BiochemistryFaculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Institute of Nutritional ScienceUniversity of Potsdam, Potsdam, Germany
Institut für Laboriatorumsmedizin IFLbBerlin, Germany.
Departments of Embryology and NephrologyBasic Medical College, Jinan University, Guangzhou, China.


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.


DPP-4; DPP-4 inhibitors; GLP-1 and SDF-1a; diabetic nephropathy

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