title: Mulberry anthocyanin extract ameliorates insulin resistance by regulating PI3K/AKT pathway in HepG2 cells and db/db mice.
abstract: This study evaluated the capacity of mulberry anthocyanin extract (MAE) on insulin resistance amelioration in HepG2 cells induced by high glucose and palmitic acid and diabetes-related metabolic changes in type 2 diabetic mice. In vitro, MAE alleviated insulin resistance in HepG2 cells and increased glucose consumption, glucose uptake and glycogen content. Enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were decreased due to PPARγ coactivator 1α (PGC-1α) and forkhead box protein O1 (FOXO1) inhibition. Furthermore, phosphorylation of protein kinase B (AKT) and glycogen synthase kinase-3β (GSK3β) in model cells was recovered after treated with MAE, leading to an up-regulation of glycogen synthase 2 (GYS2), and this effect was blocked by the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002. In vivo, MAE supplementation (50 and 125 mg/kg body weight per day) markedly decreased fasting blood glucose, serum insulin, leptin, triglyceride and cholesterol levels and increased adiponectin levels in db/db mice. The improvement of related metabolic parameters was in part associated with the impact of MAE on activating AKT and downstream targets in liver, skeletal muscle and adipose tissues. In summary, these findings suggest that MAEs have potential benefits on improving dysfunction in diabetic mice and mitigating insulin resistance in HepG2 cells via activation of PI3K/AKT pathways.
authors: Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310058, People's Republic of China; Zhejiang Key Laboratory for Agro-food Processing, Zhejiang University, Hangzhou 310058, People's Republic of China; Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, People's Republic of China.
authors: Fujie
authors: F
authors: Yan
authors: Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China.
authors: Guanhai
authors: G
authors: Dai
authors: Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310058, People's Republic of China; Zhejiang Key Laboratory for Agro-food Processing, Zhejiang University, Hangzhou 310058, People's Republic of China; Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, People's Republic of China. Electronic address: foodbiotech@zju.edu.cn.
authors: Xiaodong
authors: X
authors: Zheng
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000008:administration & dosage / Q000032:analysis / Q000302:isolation & purification / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism; D019587:Dietary Supplements; D005638:Fruit / Q000737:chemistry; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D031625:Morus / Q000737:chemistry*; D058539:Phosphatidylinositol 3-Kinase / Q000737:chemistry / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms
chemical_list: D000872:Anthocyanins; D007004:Hypoglycemic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Glucose metabolism; HepG2 cells; Mulberry anthocyanins; db/db mice