Metformin improves insulin resistance, liver healthy and abnormal hepatic glucolipid metabolism via IR/PI3K/AKT pathway in Ctenopharyngodon idella fed a high-carbohydrate diet

IF 3.9 3区 环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
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Abstract

The effects and underlying mechanisms of metformin which can improve glucose homeostasis of fish have rarely been explored. This experiment aimed to explore the influence of metformin on growth performance, body composition, liver health, hepatic glucolipid metabolic capacity and IR/PI3K/AKT pathway in grass carp (Ctenopharyngodon idella) fed high-carbohydrate diets. A normal diet (Control) and high carbohydrate diets with metformin supplementation (0.00 %, 0.20 %, 0.40 %, 0.60 % and 0.80 %) were configured. Six groups of healthy fish were fed with the experimental diet for eight weeks. The results showed that the growth performance of grass carp was impaired in high carbohydrate diet. Impairment of IR/PI3K/AKT signalling pathway reduced insulin sensitivity, while hepatic oxidative stress damage and decreased immunity affected liver metabolic function. The glycolysis and lipolysis decrease while the gluconeogenesis and fat synthesis increase, which triggers hyperglycaemia and lipid deposition in the body. Metformin supplementation restored the growth performance of grass carp. Metformin improved IR/PI3K/AKT pathway signalling and alleviated insulin resistance, while liver antioxidant capacity and immunity were enhanced resulting in the restoration of liver health. The elevation of glycolysis and lipolysis maintains glycaemic homeostasis and reduces lipid deposition, respectively. These results suggest that metformin supplementation restores liver health and activates the IR/PI3K/AKT signalling pathway, ameliorating insulin resistance and glucose-lipid metabolism disorders caused by a high-carbohydrate diet. As judged by HOMA-IR, the optimum supplementation level of metformin in grass carp (C. idella) fed a high-carbohydrate diet is 0.67 %.

Abstract Image

二甲双胍通过IR/PI3K/AKT途径改善高碳水化合物饮食栉水母的胰岛素抵抗、肝脏健康和肝糖脂代谢异常。
二甲双胍能改善鱼类的糖稳态,但其作用和内在机制却鲜有研究。本实验旨在探讨二甲双胍对草鱼(Ctenopharyngodon idella)生长性能、体成分、肝脏健康、肝糖脂代谢能力和IR/PI3K/AKT通路的影响。配置了正常日粮(对照组)和添加二甲双胍的高碳水化合物日粮(0.00 %、0.20 %、0.40 %、0.60 %和0.80 %)。六组健康鱼连续八周摄入实验日粮。结果表明,草鱼在高碳水化合物饲料中的生长性能受到影响。IR/PI3K/AKT信号通路受损降低了胰岛素敏感性,肝脏氧化应激损伤和免疫力下降影响了肝脏代谢功能。糖酵解和脂肪分解减少,而糖元生成和脂肪合成增加,从而引发高血糖和体内脂质沉积。补充二甲双胍可恢复草鱼的生长性能。二甲双胍改善了IR/PI3K/AKT通路信号传导,缓解了胰岛素抵抗,同时提高了肝脏抗氧化能力和免疫力,从而恢复了肝脏健康。糖酵解和脂肪分解的提高分别维持了血糖平衡和减少了脂质沉积。这些结果表明,补充二甲双胍可恢复肝脏健康,激活IR/PI3K/AKT信号通路,改善高碳水化合物饮食引起的胰岛素抵抗和糖脂代谢紊乱。根据 HOMA-IR 的判断,喂食高碳水化合物饲料的草鱼补充二甲双胍的最佳水平为 0.67%。
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来源期刊
CiteScore
7.50
自引率
5.10%
发文量
206
审稿时长
30 days
期刊介绍: Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.
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