title: MDG-1, a polysaccharide from Ophiopogon japonicus exerts hypoglycemic effects through the PI3K/Akt pathway in a diabetic KKAy mouse model.
abstract: BACKGROUND
  Ophiopogon japonicus is a traditional Chinese medicine that might be helpful for the treatment of type 2 diabetes. Recent studies have confirmed its beneficial properties, but not the mechanism of action.
  
  
  OBJECTIVE
  In this study, we examined the effects of a water-soluble β-d-fructan (MDG-1) from O. japonicus on type 2 diabetes through the PI3K/Akt pathway in a diabetic KKAy mouse model.
  
  
  METHODS
  MDG-1 was extracted from the tube root of O. japonicus and purified as described previously (Xu et al., 2005). The KKAy mice were gavaged once daily with either distilled water, MDG-1or rosiglitazonefor 8 weeks. Blood glucose levels were tested regularly for the fed and fasted mice. In order to evaluate the effect of MDG-1 on disease progression, the proteins of InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 were detected by Western blotting and serum TG, TC, HDL-C, LDL-C were also dertermined.
  
  
  RESULTS
  MDG-1 reduced the hyperglycemia, hyperinsulinemia and hyperlipidemia in the KKAy mice. The oral glucose tolerance test (OGTT) and the level of insulin in the serun showed that insulin resistance in KKAy mice was ameliorated after MDG-1 treated. After 8 weeks treatment with 300mg/kg MDG-1, the content of triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) the serum decreased significantly. Meanwhile high density lipoprotein cholesterol (HDL-C) content increased notably. MDG-1 did not have any effect on total cholesterol (TC) content in the serum, whereas rosiglitazone significantly decreased the TC content. In addition, MDG-1 upregulates the phosphoinositide 3-kinase p85 subunit, Akt, insulin receptor (InsR), insulin receptor substrate-1 (IRS-1) and Glut-4 expression, but downregulates glycogen synthase kinase 3β expression.
  
  
  CONCLUSIONS
  These data indicate that MDG-1 has remarkable anti-diabetic activity through the InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 signaling pathway. We believe that MDG-1 is a promising anti-diabetic compound that will be helpful for the treatment of T2DM.
authors: Department of TCM, Shanghai University of Traditional Chinese Medicine, Pudong, Shanghai 201203, People's Republic of China.
authors: Ling-Yi
authors: LY
authors: Wang
authors: Yuan
authors: Y
authors: Wang
authors: De-Sheng
authors: DS
authors: Xu
authors: Ke-Feng
authors: KF
authors: Ruan
authors: Yi
authors: Y
authors: Feng
authors: Shuo
authors: S
authors: Wang
mesh_terms: D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D006946:Hyperinsulinism / Q000188:drug therapy / Q000378:metabolism; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D008810:Mice, Inbred C57BL; D031441:Ophiopogon / Q000737:chemistry*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018517:Plant Roots; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010936:Plant Extracts; D011134:Polysaccharides; C495693:Slc2a4 protein, mouse; D045162:Thiazolidinediones; D014280:Triglycerides; C517472:polysaccharide MDG-1; D000077154:Rosiglitazone; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3