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Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

by Qichen Yuan 1,2, Biyuan Zhan 2, Rui Chang 2, Min Du 1,3 and Xueying Mao 1,2,*
1
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China
2
Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, Ministry of Education, China Agricultural University, Beijing 100083, China
3
Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(1), 220; https://doi.org/10.3390/nu12010220
Received: 23 November 2019 / Revised: 24 December 2019 / Accepted: 7 January 2020 / Published: 15 January 2020
(This article belongs to the Section Nutrition and Metabolism)
This study evaluated the effects and the underlying mechanisms of casein glycomacropeptide hydrolysate (GHP) on high-fat diet-fed and streptozotocin-induced type 2 diabetes (T2D) in C57BL/6J mice. Results showed that 8-week GHP supplementation significantly decreased fasting blood glucose levels, restored insulin production, improved glucose tolerance and insulin tolerance, and alleviated dyslipidemia in T2D mice. In addition, GHP supplementation reduced the concentration of lipopolysaccharides (LPSs) and pro-inflammatory cytokines in serum, which led to reduced systematic inflammation. Furthermore, GHP supplementation increased muscle glycogen content in diabetic mice, which was probably due to the regulation of glycogen synthase kinase 3 beta and glycogen synthase. GHP regulated the insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B pathway in skeletal muscle, which promoted glucose transporter 4 (GLUT4) translocation. Moreover, GHP modulated the overall structure and diversity of gut microbiota in T2D mice. GHP increased the Bacteroidetes/Firmicutes ratio and the abundance of S24-7, Ruminiclostridium, Blautia and Allobaculum, which might contribute to its antidiabetic effect. Taken together, our findings demonstrate that the antidiabetic effect of GHP may be associated with the recovery of skeletal muscle insulin sensitivity and the regulation of gut microbiota.
Keywords: casein glycomacropeptide hydrolysate; diabetes; insulin signaling pathway; skeletal muscle; gut microbiota; inflammation casein glycomacropeptide hydrolysate; diabetes; insulin signaling pathway; skeletal muscle; gut microbiota; inflammation
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Yuan, Q.; Zhan, B.; Chang, R.; Du, M.; Mao, X. Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota. Nutrients 2020, 12, 220.

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