Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy
- 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 membranebound 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-1Diabetic 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 membranebound 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.…
Author details: | Ahmed Abdallah Abdalrahman Mohamed HasanORCiDGND, Berthold HocherORCiDGND |
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DOI: | https://doi.org/10.1530/JME-17-0005 |
ISSN: | 0952-5041 |
ISSN: | 1479-6813 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/28420715 |
Title of parent work (English): | Journal of Molecular Endocrinology |
Publisher: | Bioscientifica LTD |
Place of publishing: | Bristol |
Publication type: | Review |
Language: | English |
Date of first publication: | 2017/04/18 |
Publication year: | 2017 |
Release date: | 2022/04/14 |
Tag: | DPP-4; DPP-4 inhibitors; GLP-1 and SDF-1a; diabetic nephropathy |
Volume: | 59 |
Number of pages: | 10 |
First page: | R1 |
Last Page: | R10 |
Funding institution: | Boehringer Ingelheim; manufacturer of linagliptin |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Peer review: | Referiert |
Publishing method: | Open Access / Bronze Open-Access |