Effects of topiramate on diabetes mellitus induced by streptozotocin in rats

Eur J Pharmacol. 2012 Jun 5;684(1-3):161-7. doi: 10.1016/j.ejphar.2012.03.042. Epub 2012 Apr 3.

Abstract

Topiramate currently approved for marketing as antiepileptic drug also possesses anti-diabetic activity. The aim of this study was to determine the antidiabetic effect of topiramate in a rat model of diabetes mellitus. Diabetes was induced by a single injection of streptozotocin to fasted rats. Diabetic animals were divided into untreated; insulin treated; topiramate treated with 25, 50 and 100 mg/kg; and combined insulin plus topiramate treatment in the previous doses. All medications were given once daily started after the rise of blood glucose for three weeks. Control rats were divided into untreated; vehicle treated and rats given topiramate in the previous doses. Body weight, blood-glucose and insulin levels were measured. Histopathological examination, immunohistochemical and morphometric studies of islets of the pancreas were done. Topiramate 50 and 100mg/kg resulted in a significant decrease in the blood glucose and increase in the insulin levels as well as the number of islets and the count and mass of beta cells. Combined treatment to diabetic rats with insulin and topiramate induced a better response than either alone. Further experimental and clinical studies are needed to explore the different mechanisms of action of topiramate as antidiabetic both in insulin dependent and non-insulin-dependent diabetes mellitus.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Fructose / analogs & derivatives*
  • Fructose / pharmacology
  • Fructose / therapeutic use
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Topiramate

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Topiramate
  • Fructose