TY - JOUR

T1 - Impact of type 1 diabetes mellitus and sitagliptin treatment on the neuropeptide Y system of rat retina

AU - Campos, Elisa J.

AU - Martins, João

AU - Brudzewsky, Dan

AU - Correia, Sandra

AU - Santiago, Ana R.

AU - Woldbye, David P.D.

AU - Ambrósio, António F.

PY - 2018

Y1 - 2018

N2 - Background: Neuropeptide Y (NPY) is a neuromodulator that is expressed in the retina. Increasing evidence suggests that NPY has pronounced anti-inflammatory effects, which might depend on the inhibition of dipeptidyl-peptidase-IV (DPP-IV). The aim of this study was to investigate the impact of type 1 diabetes mellitus (DM) and sitagliptin, a DPP-IV inhibitor, on the NPY system in the retina using an animal model. Methods: Type 1 DM was induced in male Wistar rats by an intraperitoneal injection of streptozotocin. Starting 2weeks after DM onset, animals were treated orally with sitagliptin (5mg/kg.day) for 2weeks. The expression of NPY and NPY receptors (Y1, Y2 and Y5 receptors) was measured by quantitative polymerase chain reaction, Western blot and/or enzyme-linked immunosorbent assay. The immunoreactivity of NPY and NPY receptors was evaluated by immunohistochemistry, and the [35S]GTPγS binding assay was used to assess the functional binding of NPY receptors. Results: DM decreased the mRNA levels of NPY in the retina, as well as the protein levels of NPY and Y5 receptor. No changes were detected in the localization of NPY and NPY receptors in the retina and in the functional binding of NPY to all receptors. Sitagliptin alone reduced retinal NPY mRNA levels. The effects of DM on the NPY system were not affected by sitagliptin. Conclusion: DM modestly affects the NPY system in the retina and these effects are not prevented by sitagliptin treatment. These observations suggest that DPP-IV enzyme is not underlying the NPY changes detected in the retina induced by type 1 DM.

AB - Background: Neuropeptide Y (NPY) is a neuromodulator that is expressed in the retina. Increasing evidence suggests that NPY has pronounced anti-inflammatory effects, which might depend on the inhibition of dipeptidyl-peptidase-IV (DPP-IV). The aim of this study was to investigate the impact of type 1 diabetes mellitus (DM) and sitagliptin, a DPP-IV inhibitor, on the NPY system in the retina using an animal model. Methods: Type 1 DM was induced in male Wistar rats by an intraperitoneal injection of streptozotocin. Starting 2weeks after DM onset, animals were treated orally with sitagliptin (5mg/kg.day) for 2weeks. The expression of NPY and NPY receptors (Y1, Y2 and Y5 receptors) was measured by quantitative polymerase chain reaction, Western blot and/or enzyme-linked immunosorbent assay. The immunoreactivity of NPY and NPY receptors was evaluated by immunohistochemistry, and the [35S]GTPγS binding assay was used to assess the functional binding of NPY receptors. Results: DM decreased the mRNA levels of NPY in the retina, as well as the protein levels of NPY and Y5 receptor. No changes were detected in the localization of NPY and NPY receptors in the retina and in the functional binding of NPY to all receptors. Sitagliptin alone reduced retinal NPY mRNA levels. The effects of DM on the NPY system were not affected by sitagliptin. Conclusion: DM modestly affects the NPY system in the retina and these effects are not prevented by sitagliptin treatment. These observations suggest that DPP-IV enzyme is not underlying the NPY changes detected in the retina induced by type 1 DM.

KW - Diabetes

KW - Neuropeptide Y system

KW - Retina

KW - Sitagliptin

U2 - 10.1111/ceo.13176

DO - 10.1111/ceo.13176

M3 - Journal article

C2 - 29442423

AN - SCOPUS:85043287395

VL - 46

SP - 783

EP - 795

JO - Clinical and Experimental Ophthalmology

JF - Clinical and Experimental Ophthalmology

SN - 1442-6404

IS - 7

ER -