title: Hybrid of 1-deoxynojirimycin and polysaccharide from mulberry leaves treat diabetes mellitus by activating PDX-1/insulin-1 signaling pathway and regulating the expression of glucokinase, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in alloxan-induced diabetic mice.
abstract: BACKGROUND
  1-Deoxynojirimycin (DNJ) discovered from mulberry trees has been reported to be a potent inhibitor of intestinal α-glycosidases (sucrase, maltase, glucoamylase), and many polysaccharides were useful in protecting against alloxan-induced pancreatic islets damage through their scavenging ability. This study was aimed to evaluate the therapeutic effect and potential mechanism(s) of the hybrid of DNJ and polysaccharide (HDP) from mulberry leaves on alloxan-induced diabetic mice.
  
  
  METHODS
  Daily oral treatment with HDP (150 mg/kg body weight) to diabetic mice for 12 weeks, body weight and blood glucose were determined every week, oral glucose tolerance test was performed after 4 and 8 weeks, biochemical values were measured using assay kits and gene expressions were investigated by RT-PCR.
  
  
  RESULTS
  A significant decline in blood glucose, glycosylated hemoglobin, triglyceride, aspartate transaminase and alanine transaminase levels and an evident increase in body weight, plasma insulin level and high density lipoprotein were observed in HDP treated diabetic mice. The polysaccharide (P1) showed a significant scavenging hydroxyl radicals and superoxide anion radical effects in vitro, which indicated that P1 could protect alloxan-induced pancreatic islets from damage by scavenging the free radicals and repaired the destroyed pancreatic β-cells. Pharmacokinetics assay showed that DNJ could be absorbed from the gastrointestinal mucosa and diffused rapidly into the liver, resulted in postprandial blood glucose decrease and alleviated the toxicity caused by sustained supra-physiological glucose to pancreatic β-cells. RT-PCR results indicated that HDP could modulate the hepatic glucose metabolism and gluconeogenesis by up/down-regulating the expression of rate-limiting enzymes (glucokinase, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in liver and up-regulating the pancreatic and duodenal homeobox factor-1 (PDX-1), insulin-1 and insulin-2 expressions in pancreas.
  
  
  CONCLUSIONS
  These findings suggested that HDP has complimentary potency to develop an antihyperglycemic agent for treatment of diabetes mellitus.
authors.affiliation: Sericultural Research Institute, Zhejiang Academy of Agricultural Science, No. 198 Shiqiao Road, Hangzhou 310021, China.
authors.forename: You-Gui
authors.initials: YG
authors.lastname: Li
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Ji
authors.forename: Shi
authors.initials: S
authors.lastname: Zhong
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Lv
authors.forename: Tian-Bao
authors.initials: TB
authors.lastname: Lin
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.forename: Gui-Yan
authors.initials: GY
authors.lastname: Hu
mesh_terms: D017485:1-Deoxynojirimycin / Q000494:pharmacology / Q000627:therapeutic use*; D000496:Alloxan; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism; D005951:Glucose Tolerance Test; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D031625:Morus / Q000737:chemistry*; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry*; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; D007328:Insulin; D011134:Polysaccharides; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D017485:1-Deoxynojirimycin; D000496:Alloxan; D005941:Glucokinase; D005952:Glucose-6-Phosphatase; D019764:Phosphoenolpyruvate Carboxykinase (ATP)