title: Genistein and daidzein prevent diabetes onset by elevating insulin level and altering hepatic gluconeogenic and lipogenic enzyme activities in non-obese diabetic (NOD) mice.
abstract: BACKGROUND
  Non-obese diabetic (NOD) mice are regarded as being excellent animal models of human type 1 diabetes or insulin dependent diabetes (IDDM). This study investigated the beneficial effects of genistein and daidzein on IDDM, an autoimmune disease.
  
  
  METHODS
  Female NOD mice were divided into control, genistein (0.02%, w/w) and daidzein (0.02%, w/w) groups. Blood glucose level, plasma biomarkers, hepatic glucose and lipid regulating enzyme activities and pancreas immunohistochemistry analysis were examined after a 9-week experimental period.
  
  
  RESULTS
  Blood glucose levels of genistein and daidzein groups were 40 and 36% of control value at the end of study (9th week). The genistein and daidzein supplements increased insulin/glucagon ratio and C-peptide level with preservation of insulin staining beta-cell of pancreas in the NOD mice. In the liver, genistein and daidzein supplements resulted in lowering glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities, while increasing two lipogenic enzymes activities, malic enzyme and glucose-6-phosphate dehydrogenase (G6PD), compared to the control group. Significantly, genistein and daidzein supplementation lowered the activities of fatty acid beta-oxidation and carnitine palmitoyltransferase (CPT) in these mice. Genistein and daidzein also improved plasma triglyceride and free fatty acid (FFA) concentrations compared to the control group.
  
  
  CONCLUSIONS
  These results suggest that genistein and daidzein play important roles in regulation of glucose homeostasis in type 1 diabetic mice by down-regulating G6Pase, PEPCK, fatty acid beta-oxidation and CPT activities, while up-regulating malic enzyme and G6PD activities in liver with preservation of pancreatic beta-cells. The supplementation of genistein and daidzein are seemingly helpful for preventing IDDM onset.
authors.affiliation: Department of Food Science and Nutrition, Kyungpook National University, Daegu, 702-701, Republic of Korea.
authors.forename: M S
authors.initials: MS
authors.lastname: Choi
authors.forename: U J
authors.initials: UJ
authors.lastname: Jung
authors.forename: J
authors.initials: J
authors.lastname: Yeo
authors.forename: M J
authors.initials: MJ
authors.lastname: Kim
authors.forename: M K
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D001806:Blood Urea Nitrogen; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D019833:Genistein / Q000627:therapeutic use*; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D007328:Insulin / Q000032:analysis / Q000097:blood*; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects; D007529:Isoflavones / Q000627:therapeutic use*; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D007529:Isoflavones; D008055:Lipids; C004742:daidzein; D005934:Glucagon; D019833:Genistein; D008291:Malate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005952:Glucose-6-Phosphatase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)