CB-1R and GLP-1R gene expressions and oxidative stress in the liver of diabetic rats treated with sitagliptin

Coşkun, Zeynep Mine; Koyutürk, Meral; Karabulut, Sezin; Bolkent, Şehnaz

doi:10.1016/j.pharep.2017.03.013

Cited by 9 publications

(6 citation statements)

References 50 publications

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“…We showed that MDA formation was reduced after STG treatment also in livers subjected to IR. However, without pathology such as IR or diabetes, STG seems to have an opposite effect and increase the accumulation of TBARS, what was also noticed by other authors [29, 43].…”

Section: Discussionsupporting

confidence: 75%

Sitagliptin-Dependent Differences in the Intensity of Oxidative Stress in Rat Livers Subjected to Ischemia and Reperfusion

Trocha

Krzystek−Korpacka

Merwid-Ląd

et al. 2019

Oxidative Medicine and Cellular Longevity

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Purpose Ischemia/reperfusion (IR) is the main cause of liver damage after transplantation. We evaluated the effect of sitagliptin (STG) on oxidative stress parameters in the rat liver under IR. Methods Rats were treated with STG (5 mg/kg) (S and SIR) or saline solution (C and CIR). Livers from CIR and SIR were subjected to ischemia (60 min) and reperfusion (24 h). During reperfusion, aminotransferases (ALT and AST) were determined in blood samples. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), paraoxonase-1 (PON1), glutathione peroxidase (GPx), and the mRNA expression of SOD1 were determined in liver homogenates after reperfusion. Different regions of livers were also histologically evaluated. Results The PON1 activity was higher, and the TBARS level was lower in SIR than in CIR. There was an inverse relationship between TBARS and PON1 levels in the whole cohort. The GPx activity was lower in ischemic than in nonischemic groups regardless of the STG treatment. In SIR, the SOD1 activity was higher compared to that in CIR. In S, the expression of SOD1 mRNA was the highest of all examined groups and positively correlated with the SOD1 activity in the whole animal cohort. During IR aminotransferases, the activity in the drug-treated group was lower in all examined points of time. In drug-treated groups, the percentage of steatosis was higher than that in nontreated groups regardless of IR. Conclusions The protective effect of STG on the rat liver, especially its antioxidant properties, was revealed under IR conditions.

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Section: Discussionsupporting

confidence: 75%

Sitagliptin-Dependent Differences in the Intensity of Oxidative Stress in Rat Livers Subjected to Ischemia and Reperfusion

Trocha

Krzystek−Korpacka

Merwid-Ląd

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…Inflammatory reactions encompass the transfer of liquid and cells from blood vessels to tissue, and protection and repair of tissue. (14). It is caused by the interaction of different cells at injured tissues, including neurons, astrocytes, myofibroblasts, smooth muscle cells, endothelial cells and hemocytes (27).…”

Section: Discussionmentioning

confidence: 99%

“…Inflammatory reactions inhibit neuron reclamation and functional rehabilitation following cerebral apoplexy (12,13). At the early stage of cerebral ischemia-reperfusion, the blood-brain barrier is damaged, leading to an increase in vascular endothelium permeability, and the exudation of albumin and other macromolecular proteins into the blood, which subsequently cause local edema (14).…”

Section: Studies Have Reported That Inflammatory Reactions and Cellmentioning

confidence: 99%

MicroRNA-132 modifies angiogenesis in patients with ischemic cerebrovascular disease by suppressing the NF‑κB and VEGF pathway

Che

Zhang

et al. 2017

Mol Med Report

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In the present study, the expression of microRNA (miR)‑132 and the mechanism by which it modifies angiogenesis in patients with ischemic cerebrovascular disease (ICD) was investigated. RNA isolation and reverse transcription‑quantitative polymerase chain reaction were used to measure miR‑132 expression in patients with ICD. Inflammatory factors were measured using ELISA kits and western blotting measured B‑cell lymphoma‑2 (Bcl‑2)‑associated X/Bcl‑2 ratio (Bax/Bcl‑2 ratio), nuclear factor (NF)‑κB p65, matrix metalloproteinase‑9 (MMP‑9), vascular cell adhesion molecule‑1 (VCAM‑1) and protein expression of inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF) protein expression. miR‑132 expression in patients with ICD was lower compared with healthy volunteers. PC12 cells were used to create an oxygen glucose deprivation (OGD) model. miR‑132 overexpression in an in vitro model was able to reduce tumor necrosis factor‑a, interleukin (IL)‑1β, IL‑6, IL‑8, cyclooxygenase‑2, caspase‑3 and caspase‑9 levels, suppress Bax/Bcl‑2 ratio, NF‑κB p65, MMP‑9, VCAM‑1, iNOS, VEGF protein expression. The results suggested that miR‑132 may modify angiogenesis in patients with ICD by suppressing the NF‑κB pathway and promoting the VEGF pathway, and may develop into a therapy for ICD in future research.

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“…GLP‐1R and CB1 play a role in energy metabolism and appetite control . The mRNA expression of both Glp1r and Cnr1 was found to decrease in the liver of diabetic neonatal rats . Emerging evidence has shown important interactions between endocannabinoid systems and ghrelin and their effect on food intake.…”

Section: Discussionmentioning

confidence: 99%

Changes in the expression levels of CB1 and GLP‐1R mRNAs and microRNAs 33a and 122 in the liver of type 2 diabetic rats treated with ghrelin

Coşkun

Beydogan

Bolkent

2019

J Biochem & Molecular Tox

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The aim of the study is to clarify the effect of ghrelin treatment on the messenger RNA (mRNA) expression of the cannabinoid receptor 1 (Cnr1/CB1) and glucagon‐like peptide 1 receptor (Glp1r/GLP‐1R) as well as microRNAs (miR)‐122 and miR‐33a in the liver of rats with type 2 diabetes mellitus (T2DM). Adult Sprague‐Dawley rats were divided into three groups: control (n = 7), T2DM (n = 7), and treatment (n = 7). Control animals received tap water. T2DM was induced by feeding 10% fructose in drinking water for 2 weeks followed by a single injection of streptozotocin (40 mg/kg, intraperitoneally [IP]). In the treatment group, diabetic rats were injected ghrelin (25 μg/kg, IP) for 14 days. Serum lipid profiles were evaluated, and mRNA expression levels of Cnr1 and Glp1r in the liver were detected using quantitative real‐time polymerase chain reaction (RT‐qPCR). In addition, miR‐122 and miR‐33a levels were measured using RT‐qPCR. Serum triglycerides, low‐density lipoprotein cholesterol, and very‐low‐density lipoprotein cholesterol significantly increased in the T2DM group compared with control rats but ghrelin treatment showed no effect on serum lipid levels. The mRNA expression levels of Cnr1 and Glp1r decreased in the T2DM group compared with the control group. These reductions were significantly increased in the T2DM group treated with ghrelin. Furthermore, the increase in miR‐33a expression level was reduced in the treatment group compared to rats with T2DM. Our findings suggested that ghrelin treatment may alter the mRNA expression levels of CB1 and GLP‐1R in the liver of rats with T2DM. The mRNA levels of Cnr1 and Glp1r may inversely correlate with the expression level of miR‐33a but not miR‐122.

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CB-1R and GLP-1R gene expressions and oxidative stress in the liver of diabetic rats treated with sitagliptin

Abstract: Our findings indicate that sitagliptin treatment regulates GLP-1R and CB-1R gene expressions, which are associated with appetite regulation in diabetic rat, and may decrease oxidative stress and liver tissue damage.

Cited by 9 publications

References 50 publications

Sitagliptin-Dependent Differences in the Intensity of Oxidative Stress in Rat Livers Subjected to Ischemia and Reperfusion

Sitagliptin-Dependent Differences in the Intensity of Oxidative Stress in Rat Livers Subjected to Ischemia and Reperfusion

MicroRNA-132 modifies angiogenesis in patients with ischemic cerebrovascular disease by suppressing the NF‑κB and VEGF pathway

Changes in the expression levels of CB1 and GLP‐1R mRNAs and microRNAs 33a and 122 in the liver of type 2 diabetic rats treated with ghrelin

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