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

Background and 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. Material and 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 R T-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.

Gmelina arboreaRoxb. (Family: Verbenaceae) Extract Upregulates theβ-Cell Regeneration in STZ Induced Diabetic Rats

“…In addition, the antidiabetic mechanisms of the extract were determined through the estimation of serum concentration of insulin, C-peptide, and detailed assessments of histopathology and immunohistochemistry of the pancreas. Glibenclamide was used as the standard drug in the present study and it has been widely accepted as a standard drug in diabetic animal experiments associated with mild, severe hyperglycemia [ 11 ].…”

Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review

“…Most of the studies for GLUT1 evaluation in these models were carried out in streptozotocin (STZ) rats. They predominantly reported higher GLUT1 protein [79][80][81][82] and corresponding mRNA [81][82][83][84][85] contents in the whole kidney and increased GLUT1 protein [86,87] and mRNA [86,88,89] in the cortex. Nonetheless, these studies are yet controversial [22,67,[90][91][92][93].…”

Hypoglycaemic Effect of Glibenclamide: A Critical Study on the Basis of Creatinine and Lipid Peroxidation Status of Streptozotocin-induced Diabetic Rat

“…In addition to this direct action, it also shows extra pancreatic effects [19] . This drug binds to the sulfonylurea receptor 1 (SUR 1) [20] , a regulatory subunit of the ATP-sensitive potassium channels (K ATP ) in the pancreatic beta cells [21,22] . This inhibition causes cell membrane depolarization and opens the voltagedependent calcium channels.…”

“…On the 20 th d of the experiment, glibenclamide treated rats showed a reduced fasting blood glucose level and the treatment was stopped for a five days (20)(21)(22)(23)(24)(25) th d). After that there was an elevated blood glucose level in the glibenclamide treated groups when they were kept untreated.…”

“…Studies suggest that glibenclamide shows insulin dependent blood glucose lowering effect [21] especially in STZ-induced type 1 diabetic model [18] . This may be due to the insulin stimulating effect of this medicine in STZ-induced diabetes or clinical diabetes.…”