title: Vernonia amygdalina simultaneously suppresses gluconeogenesis and potentiates glucose oxidation via the pentose phosphate pathway in streptozotocin-induced diabetic rats.
abstract: BACKGROUND
  This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA.
  
  
  METHODS
  The chloroform fraction of VA (200 mg/kg and 400 mg/kg body weight) was administered to SDRs for 7 and 14 days. Thereafter, the expression (transcription) of key carbohydrate regulatory genes was evaluated in selected tissues - adipose, muscle and liver. Also, the body weight and blood glucose changes were monitored.
  
  
  RESULTS
  A 14-day administration of 200 mg and 400 mg of the extract and metformin (500 mg/kg) showed a striking decrease (P <0.05) in the expression of the gluconeogenic enzymes - fructose 1,6-bisphosphatase, phosphoenol pyruvate carboxykinase and glucose 6-phosphatase in the liver and muscle compared to the diabetic control. These genes were highly expressed in tissues of untreated diabetic rats (P <0.05) indicating severe gluconeogenesis. Furthermore, the extract as well as metformin significantly increased glucose oxidation via the pentose phosphate pathway (PPP) i.e. increased expression of the glucose 6-phosphate dehydrogenase (G6PDH) gene (P <0.05) in the liver. Conversely, the expression of the G6PDH in the muscle and adipose tissues significantly decreased (P <0.05), suggesting enhanced utilization of NADPH and ribose in the clearance of reactive oxygen species and for expression of other relevant genes respectively. Also, transcription of the cell proliferation regulatory enzyme, phosphatidylinositol 3-kinase increased in the liver, but decreased in the muscle and adipose tissues (P <0.05) upon treatment with the extract or metformin, implying that the liver responded to the VA and metformin treatments more than other organs. The extract administration also caused a decrease in the expression of key enzymes of glycolysis namely hexokinase and phosphofructokinase, suggestive of a glucose sparing for ribose and NADPH production in PPP.
  
  
  CONCLUSIONS
  Overall, data obtained in this study suggest that VA exerts little or no effect on glycolysis; rather, it may achieve its anti-diabetic action by a simultaneous suppression of gluconeogenesis and potentiation of glucose oxidation via PPP pathway, almost exclusively in the liver.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia. dratangwho@gmail.com.
authors.forename: Item Justin
authors.initials: IJ
authors.lastname: Atangwho
authors.forename: Khoo Boon
authors.initials: KB
authors.lastname: Yin
authors.forename: Muhammad Ihtisham
authors.initials: MI
authors.lastname: Umar
authors.forename: Mariam
authors.initials: M
authors.lastname: Ahmad
authors.forename: Mohd Zaini
authors.initials: MZ
authors.lastname: Asmawi
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D015870:Gene Expression; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006593:Hexokinase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D035741:Vernonia
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D005954:Glucosephosphate Dehydrogenase; D019869:Phosphatidylinositol 3-Kinases; D006593:Hexokinase; D005952:Glucose-6-Phosphatase; D005947:Glucose