The DPP4 inhibitor linagliptin protects from experimental diabetic retinopathy

• Verfasst von: Dietrich, Nadine [VerfasserIn]
• Verfasst von: Kolibabka, Matthias [VerfasserIn]
• Verfasst von: Bugert, Petra [VerfasserIn]
• Verfasst von: Kaiser, Ulrike [VerfasserIn]
• Verfasst von: Lin, Jihong [VerfasserIn]
• Verfasst von: Fleming, Thomas [VerfasserIn]
• Verfasst von: Morcos, Michael [VerfasserIn]
• Verfasst von: Schlotterer, Andrea [VerfasserIn]
• Verfasst von: Hammes, Hans-Peter [VerfasserIn]
• Titel: The DPP4 inhibitor linagliptin protects from experimental diabetic retinopathy
• Verf.angabe: Nadine Dietrich, Matthias Kolibabka, Stephanie Busch, Petra Bugert, Ulrike Kaiser, Jihong Lin, Thomas Fleming, Michael Morcos, Thomas Klein, Andrea Schlotterer, Hans-Peter Hammes
• E-Jahr: 2016
• Jahr: December 12, 2016
• Umfang: 17 S.
• Fussnoten: Gesehen am 27.02.2019
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2016
• Band/Heft Quelle: 11(2016,12) Artikel-Nummer e0167853, 17 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0167853
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Caenorhabditis elegans
• Sach-SW: Diabetes mellitus
• Sach-SW: Diabetic retinopathy
• Sach-SW: Enzyme-linked immunoassays
• Sach-SW: Gene expression
• Sach-SW: Glucose
• Sach-SW: Pericytes
• Sach-SW: Retina
• K10plus-PPN: 1588179907

Abstract

Background/aims Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear. Methods Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks), DPP4 activity (fluorometric assay), GLP-1 (ELISA), methylglyoxal (LC-MS/MS), acellular capillaries and pericytes (quantitative retinal morphometry), SDF-1a and heme oxygenase-1 (ELISA), HMGB-1, Iba1 and Thy1.1 (immunohistochemistry), nuclei in the ganglion cell layer, GFAP (western blot), and IL-1beta, Icam1, Cxcr4, catalase and beta-actin (quantitative RT-PCR) were determined. In C. elegans, neuronal function was determined using worm tracking software. Results Linagliptin decreased DPP4 activity by 77% and resulted in an 11.5-fold increase in active GLP-1. Blood glucose and HbA1c were reduced by 13% and 14% and retinal methylglyoxal by 66%. The increase in acellular capillaries was diminished by 70% and linagliptin prevented the loss of pericytes and retinal ganglion cells. The rise in Iba-1 positive microglia was reduced by 73% with linagliptin. In addition, the increase in retinal Il1b expression was decreased by 65%. As a functional correlate, impairment of motility (body bending frequency) was significantly prevented in C. elegans. Conclusion Our data suggest that linagliptin has a protective effect on the microvasculature of the diabetic retina, most likely due to a combination of neuroprotective and antioxidative effects of linagliptin on the neurovascular unit.