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Chao Xu Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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Xiang-Fei Li Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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Hong-Yan Tian Department of Ocean Technology, College of Marine and Biology Engineering, Yancheng Institute of Technology, Yancheng, Province Jiangsu, China

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Hua-Juan Shi Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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Ding-Dong Zhang Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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Kenneth Prudence Abasubong Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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Wen-Bin Liu Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China

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After a 12-week feeding trial, the glucose tolerance test was performed in Megalobrama amblycephala to evaluate the effects of metformin on the metabolic responses of glycolipids. Plasma insulin peaked at 2 h, then decreased to the basal value at 8–12 h post-injection. Plasma triglyceride levels and liver glycogen contents of the control group was decreased significantly during the first 2 and 1 h, respectively. Then, they returned to basal values at 12 h. During the whole sampling period, the high-carbohydrate groups had significantly higher levels of plasma metabolites and liver glycogen than those of the control group, and metformin supplementation enhanced these changes (except insulin levels). Glucose administration lowered the transcriptions of ampk α1, ampk α2, pepck, g6pase, fbpase, cpt IA and aco, the phosphorylation of Ampk α and the activities of the gluconeogenic enzymes during the first 2–4 h, while the opposite was true of glut 2, gs, gk, pk, accα and fas. High-carbohydrate diets significantly increased the transcriptions of ampk α1, ampk α2, glut 2, gs, gk, pk, accα and fas, the phosphorylation of Ampk α and the activities of the glycolytic enzymes during the whole sampling period, while the opposite was true for the remaining indicators. Furthermore, metformin significantly upregulated the aforementioned indicators (except accα and fas) and the transcriptions of cpt IA and aco. Overall, metformin benefits the glucose homeostasis of Megalobrama amblycephala fed high-carbohydrate diets through the activation of Ampk and the stimulation of glycolysis, glycogenesis and fatty acid oxidation, while depressing gluconeogenesis and lipogenesis.

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