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      Urtica Pilulifera in Treating Pre-diabetic Rat Model to Control the Blood Glucose, Lipids and Oxidative Stress

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          Abstract

          Introduction:

          Pre-diabetic precedes the development of full diabetes. Studying and identification changes in pre-diabetic conditions can give the possibility to decline the development of diabetes and treat conditions associated with diabetes such as cardiovascular diseases.

          Aim:

          The main objectives of the present study were to investigate the potential of using Urtica pilulifera in treating the pre-diabetic rat model and to investigate its anti-oxidant impact.

          Methods:

          The pre-diabetic model was induced in rats through daily giving high sucrose diet (35%) for 30 days. The extraction of U. pilulifera leaves was made as described by previous studies. Thirty male Wistar rats were randomly divided into three groups, control group (n=10), pre-diabetic group (n=10), and treated group with the extract of U. pilulifera (n=10). Control group rats received standard diet; pre-diabetic group rats received standard diet and high sucrose (35%) in drinking water, treated group rats received the same conditions as a pre-diabetic group, with intra-peritoneal injection of U. pilulifera injection on daily basis. After one month experiment, blood samples were taken from all rats and tested for glucose, triglycerides, cholesterol, GSH, TAC, and MDA.

          Results:

          Both glucose and triglycerides levels were significantly increased in pre-diabetic groups, and significantly reduced in the treated group by the extract of U.pilulifera. The cholesterol level was not significantly changed in all groups. The levels of GSH were significantly reduced in the pre-diabetic group compared with the control group. Treatment with the extract of U. pilulifera increased the levels of GSH significantly compared with the pre-diabetic group. The levels of TAC were not significantly changed between the control group and the pre-diabetic group, but significantly increased in the treated group compared with the pre-diabetic group. The levels of MDA significantly increased in the pre-diabetic group compared with the control group, and significantly reduced in the treated group compared with the control group.

          Conclusion:

          High sucrose pre-diabetic model is a good model to study diabetes at early stages, and the treatment using U. pilulifera has several benefits in reducing glucose and lipid profile lipids as well as combating oxidative stress.

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          Most cited references19

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          Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors.

          Malondialdehyde (MDA) is one of the most frequently used indicators of lipid peroxidation. To generate reliable reference intervals for plasma malondialdehyde (P-MDA), a reference sample group was established in Funen, Denmark. The group consisted of 213 individuals (107 men, 106 women), ages 20-79 years. P-MDA was measured in EDTA-treated plasma after derivatization by thiobarbituric acid (TBA) and separation on HPLC. UV detection was performed at 532 nm. A reference interval was calculated as recommended by IFCC with REFVAL 3.42. The estimated reference limits (0.025 and 0.975 fractals) for the group were 0.36 and 1.24 mumol/L. The data were analyzed for gender- and age-related differences. Analysis of variance showed no interaction between gender and age, but separate analyses showed an independent effect of gender (P = 0.03), but not of age (P = 0.11). Daily smokers had a slightly higher average concentration of P-MDA than nonsmokers (P = 0.05), and P-MDA correlated with daily exposure to cigarette smoke (r = 0.162; P = 0.03). A positive correlation was also demonstrated between P-MDA and weekly alcohol consumption (r = 0.153; P = 0.03). Within-subject and day-to-day variations of P-MDA indicated that the potential of P-MDA as a biomarker for individuals is questionable. However, on a group basis, the present data support that P-MDA may be a potential biomarker for oxidative stress.
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            The central role of glutathione in the pathophysiology of human diseases.

            Reduced glutathione (L-gamma-glutamyl-L-cysteinyl-glycine, GSH) is the prevalent low-molecular-weight thiol in mammalian cells. It is formed in a two-step enzymatic process including, first, the formation of gamma-glutamylcysteine from glutamate and cysteine, by the activity of the gamma-glutamylcysteine synthetase; and second, the formation of GSH by the activity of GSH synthetase which uses gamma-glutamylcysteine and glycine as substrates. While its synthesis and metabolism occur intracellularly, its catabolism occurs extracellularly by a series of enzymatic and plasma membrane transport steps. Glutathione metabolism and transport participates in many cellular reactions including: antioxidant defense of the cell, drug detoxification and cell signaling (involved in the regulation of gene expression, apoptosis and cell proliferation). Alterations in its concentration have also been demonstrated to be a common feature of many pathological conditions including diabetes, cancer, AIDS, neurodegenerative and liver diseases. Additionally, GSH catabolism has been recently reported to modulate redox-sensitive components of signal transduction cascades. In this manuscript, we review the current state of knowledge on the role of GSH in the pathogenesis of human diseases with the aim to underscore its relevance in translational research for future therapeutic treatment design.
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              Glucose Intolerance and Reduced Proliferation of Pancreatic β-Cells in Transgenic Pigs With Impaired Glucose-Dependent Insulinotropic Polypeptide Function

              OBJECTIVE The insulinotropic action of the incretin glucose-dependent insulinotropic polypeptide (GIP) is impaired in type 2 diabetes, while the effect of glucagon-like peptide-1 (GLP-1) is preserved. To evaluate the role of impaired GIP function in glucose homeostasis and development of the endocrine pancreas in a large animal model, we generated transgenic pigs expressing a dominant-negative GIP receptor (GIPRdn) in pancreatic islets. RESEARCH DESIGN AND METHODS GIPRdn transgenic pigs were generated using lentiviral transgenesis. Metabolic tests and quantitative stereological analyses of the different endocrine islet cell populations were performed, and β-cell proliferation and apoptosis were quantified to characterize this novel animal model. RESULTS Eleven-week-old GIPRdn transgenic pigs exhibited significantly reduced oral glucose tolerance due to delayed insulin secretion, whereas intravenous glucose tolerance and pancreatic β-cell mass were not different from controls. The insulinotropic effect of GIP was significantly reduced, whereas insulin secretion in response to the GLP-1 receptor agonist exendin-4 was enhanced in GIPRdn transgenic versus control pigs. With increasing age, glucose control deteriorated in GIPRdn transgenic pigs, as shown by reduced oral and intravenous glucose tolerance due to impaired insulin secretion. Importantly, β-cell proliferation was reduced by 60% in 11-week-old GIPRdn transgenic pigs, leading to a reduction of β-cell mass by 35% and 58% in 5-month-old and 1- to 1.4-year-old transgenic pigs compared with age-matched controls, respectively. CONCLUSIONS The first large animal model with impaired incretin function demonstrates an essential role of GIP for insulin secretion, proliferation of β-cells, and physiological expansion of β-cell mass.
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                Author and article information

                Journal
                Med Arch
                Med Arch
                Medical Archives
                Medical Archives
                Academy of Medical Sciences of Bosnia and Herzegovina
                0350-199X
                1986-5961
                June 2020
                : 74
                : 3
                : 168-171
                Affiliations
                [1 ]Faculty of Pharmacy, Zarqa University, Jordan
                [2 ]Department of Legal Medicine, Toxicology of Forensic Science and Toxicology, School of Medicine, Jordan University of Science and Technology, Jordan
                Author notes
                Corresponding author:Ahed Khatib. University of AmannJordan ahed.alkhatib2@ 123456gmail.com ORCID ID: http//www.orcid.org/0000-0000-0000-0000
                Article
                10.5455/medarh.2020.74.168-171
                7405998
                14416b18-701d-4685-8e0e-a85d5c2f9621
                © 2020 Kawther Faisal Amawi, Ahed J Alkhatib

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 March 2020
                : 30 May 2020
                Categories
                Original Paper

                pre-diabetes,oxidative stress,glucose,mda
                pre-diabetes, oxidative stress, glucose, mda

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