The Effects of Meteorin-Like Protein on Diabetic Neuropathy: In Vivo and In Vitro Model Studies

IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Furkan Yuksel, Asli Taslidere, Mete Ozcan, Cigdem Tekin, Suat Tekin
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Abstract

Diabetes is a disease characterized by insulin metabolism, and diabetic neuropathy (DN) develops as a result of prolonged hyperglycemia. Meteorin-like protein (Metrnl), which has been found to regulate insulin resistance in conducted studies, is thought to be therapeutic for type-2 diabetes. This study was conducted to investigate the efficacy of Metrnl on In Vivo and In Vitro diabetic neuropathy model. In study, 40 normoglycemic male Balb-C mice were divided into 4 groups (n = 10). Except for control, all groups received a single intraperitoneal (ip) injection of streptozotocin (STZ). After 72 h, blood glucose level was measured and animals above 250 mg/dL were considered diabetic. 14-day experiments were initiated 21 days after the onset of diabetes. Every day for 14 days, 0.9% isotonic sodium chloride was administered to DN group, and 2–4 µg/kg/day ip Metrnl was administered to treatment groups, and nociceptive behavior tests were performed simultaneously. End of experiment, animals were decapitated, and pancreatic tissues were collected. Dorsal root ganglion (DRG) isolated from Wistar Albino rats aged 1-2 days were exposed to high glucose for 24 , and the effect of Metrnl on cell viability and cellular pathway it utilizes were determined. It was observed that Metrnl injection increased the pain threshold (p < 0.05), improved oxidative stress parameters (p < 0.05), and restored histopathological damage of the pancreas (p < 0.05) compared to the DN group. Furthermore, Metrnl was detected to increase cell viability by utilizing mitogen-activated protein kinase pathway in DRG (p < 0.05). These findings suggest that Metrnl has neuroprotective and analgesic efficacy and ameliorates oxidative damage and histopathologic status of pancreas.

流星蛋白样蛋白对糖尿病神经病变的影响:体内和体外模型研究
糖尿病是一种以胰岛素代谢为特征的疾病,糖尿病神经病变(DN)是长期高血糖的结果。流星蛋白样蛋白(Metrnl),在进行的研究中被发现可以调节胰岛素抵抗,被认为对2型糖尿病有治疗作用。本研究旨在探讨美特宁对体内和体外糖尿病神经病变模型的疗效。选取血糖正常的Balb-C雄性小鼠40只,随机分为4组(n = 10)。除对照组外,其余各组均腹腔注射链脲佐菌素(STZ)。72h后,测量血糖水平,高于250mg /dL的动物视为糖尿病。糖尿病发病21天后开始14天的实验。DN组每天给予0.9%等渗氯化钠,治疗组每天给予2-4µg/kg/d的甲基亚硝胺,同时进行伤害性行为测试,共14 d。实验结束,取动物头颅,取胰腺组织。将1 ~ 2日龄Wistar白化大鼠背根神经节(Dorsal root ganglion, DRG)暴露于高糖环境24小时,观察Metrnl对细胞活力的影响及其作用途径。结果显示,与DN组相比,注射Metrnl可提高大鼠的疼痛阈值(p < 0.05),改善氧化应激参数(p < 0.05),恢复胰腺组织病理学损伤(p < 0.05)。此外,在DRG中检测到Metrnl通过丝裂原活化蛋白激酶途径提高细胞活力(p < 0.05)。这些结果表明,美特宁具有神经保护和镇痛作用,并能改善胰腺的氧化损伤和组织病理状况。
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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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