title: Comparison of the effects of glibenclamide on metabolic parameters, GLUT1 expression, and liver injury in rats with severe and mild streptozotocin-induced diabetes mellitus.
abstract: OBJECTIVE
  Glucose transport via GLUT1 protein could be one of additional mechanisms of the antidiabetic action of sulfonylureas. Here, the GLUT1 gene and the protein expression was studied in rats in the course of severe and mild streptozotocin-induced diabetes mellitus and under glibenclamide treatment.
  
  
  METHODS
  Severe and mild diabetes mellitus was induced using different streptozotocin doses and standard or high fat chow. Rats were treated with glibenclamide (2 mg/kg daily, per os for 6 weeks). The therapeutic effect of glibenclamide was monitored by measuring several metabolic parameters. The GLUT1 mRNA and the protein expression in the kidneys, heart, and liver was studied by means of real-time RT-PCR and immunohistochemistry.
  
  
  RESULTS
  The glibenclamide treatment decreased the blood glucose concentration and increased the insulin level in both models of severe and mild diabetes mellitus. Severe diabetes mellitus provoked an increase in both GLUT1 gene and protein expression in the kidneys and the heart, which was nearly normalized by glibenclamide. In the kidneys of mildly diabetic rats, an increase in the GLUT1 gene expression was neither confirmed on the protein level nor influenced by the glibenclamide treatment. In the liver of severely diabetic rats, the heart and the liver of mildly diabetic rats, the GLUT1 gene and the protein expression was changed independently of each other, which might be explained by abortive transcription, and pre- and posttranslational modifications of gene expression.
  
  
  CONCLUSIONS
  The GLUT1 expression was found to be affected by the glucose and insulin levels and can be modulated by glibenclamide in severely and mildly diabetic rats. Glibenclamide can prevent the liver damage caused by severe hyperglycemia.
authors: Department of Medical Biochemistry, Faculty of Medicine, University of Latvia, Sharlotes 1a, 1001 Riga, Latvia. sokolovska.jelizaveta@gmail.com
authors: Jelizaveta
authors: J
authors: Sokolovska
authors: Sergejs
authors: S
authors: Isajevs
authors: Olga
authors: O
authors: Sugoka
authors: Jelena
authors: J
authors: Sharipova
authors: Natalia
authors: N
authors: Paramonova
authors: Darja
authors: D
authors: Isajeva
authors: Evita
authors: E
authors: Rostoka
authors: Tatjana
authors: T
authors: Sjakste
authors: Ivars
authors: I
authors: Kalvinsh
authors: Nikolajs
authors: N
authors: Sjakste
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis* / Q000235:genetics; D005905:Glyburide / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D007004:Hypoglycemic Agents; D007328:Insulin; C495679:Slc2a1 protein, rat; D013453:Sulfonylurea Compounds; D005905:Glyburide