Effect of a novel proteoglycan PTP1B inhibitor from Ganoderma lucidum on the amelioration of hyperglycaemia and dyslipidaemia in db/db mice

• Published in: British journal of nutrition 2012-12, Vol.108 (11), p.2014-2025
• Main Authors: Wang, Chen-Dong, Teng, Bao-Song, He, Yan-Ming, Wu, Jia-Sheng, Pan, Deng, Pan, Luan-Feng, Zhang, Dan, Fan, Zhao-Hua, Yang, Hong-Jie, Zhou, Ping
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Biological and medical sciences; Cholesterol; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - isolation & purification; Drugs, Chinese Herbal - therapeutic use; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - therapeutic use; Enzymes; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Glucose; Herbal medicine; High density lipoprotein; Homeostasis; Hyperglycemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - isolation & purification; Hypoglycemic Agents - therapeutic use; Hypolipidemic Agents - administration & dosage; Hypolipidemic Agents - isolation & purification; Hypolipidemic Agents - therapeutic use; Insulin Resistance; Kinases; Lipid Metabolism - drug effects; Liver; Liver - drug effects; Liver - enzymology; Liver - metabolism; Liver Glycogen - metabolism; Low density lipoprotein; Male; Metabolic disorders; Mice; Mice, Mutant Strains; Musculoskeletal system; Nutritional Endocrinology; Organ Specificity; Pharmacology; Phosphorylation; Phosphorylation - drug effects; Protein Processing, Post-Translational - drug effects; Protein Subunits - metabolism; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; Proteins; Proteoglycans - administration & dosage; Proteoglycans - isolation & purification; Proteoglycans - therapeutic use; Receptor, Insulin - metabolism; Reishi - chemistry; Signal transduction; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114512000153

Protein tyrosine phosphatase 1B (PTP1B) is implicated in the negative regulation of the insulin signalling pathway by dephosphorylating the insulin receptor (IR) and IR substrates. Ganodermalucidum has traditionally been used for the treatment of diabetes in Chinese medicine; however, its anti-diabetic potency and mechanism in vivo is still unclear. Our previously published study reported a novel proteoglycan PTP1B inhibitor, named Fudan-Yueyang-Ganoderma lucidum (FYGL) from G. lucidum, with a half-maximal inhibitory concentration (IC50) value of 5·12 (sem 0·05) μg/ml, a protein:polyglycan ratio of 17:77 and 78 % glucose in polysaccharide, and dominant amino acid residues of aspartic acid, glycine, glutamic acid, alanine, serine and threonine in protein. FYGL is capable of decreasing plasma glucose in streptozotocin-induced diabetic mice with a high safety of median lethal dose (LD50) of 6 g/kg. In the present study, C57BL/6 db/db diabetic mice were trialed further using FYGL as well as metformin for comparison. Oral treatment with FYGL in db/db diabetic mice for 4 weeks significantly (P