Fisetin improves glucose homeostasis through the inhibition of gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats

Eur J Pharmacol. 2014 Oct 5:740:248-54. doi: 10.1016/j.ejphar.2014.06.065. Epub 2014 Jul 24.


Liver plays a vital role in blood glucose homeostasis. Recent studies have provided considerable evidence that hepatic glucose production (HGP) plays an important role in the development of fasting hyperglycemia in diabetes. From this perspective, diminution of HGP has certainly been considered for the treatment of diabetes. In the present study, we have analyzed the modulatory effects of fisetin, a flavonoid of strawberries, on the expression of key enzymes of carbohydrate metabolism in STZ induced experimental diabetic rats. The physiological criterions such as food and fluid intake were regularly monitored. The levels of blood glucose, plasma insulin, hemoglobin and glycosylated hemoglobin were analyzed. The mRNA and protein expression levels of gluconeogenic genes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined by immunoblot as well as PCR analysis. Diabetic group of rats showed significant increase in food and water intake when compared with control group of rats. Upon oral administration of fisetin as well as gliclazide to diabetic group of rats, the levels were found to be decreased. Oral administration of fisetin (10 mg/kg body weight) to diabetic rats for 30 days established a significant decline in blood glucose and glycosylated hemoglobin levels and a significant increase in plasma insulin level. The mRNA and protein expression levels of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), were decreased in liver tissues upon treatment with fisetin. The results of the present study suggest that fisetin improves glucose homeostasis by direct inhibition of gluconeogenesis in liver.

Keywords: Fisetin; Glucose 6 phosphatase; Immunoblotting; PEPCK; RT-PCR; STZ diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Carbohydrates / urine
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / metabolism*
  • Eating / drug effects
  • Flavonoids / pharmacology*
  • Flavonols
  • Gluconeogenesis / drug effects
  • Glucose / metabolism*
  • Glucose-6-Phosphatase / genetics
  • Glucose-6-Phosphatase / metabolism
  • Homeostasis / drug effects
  • Hypoglycemic Agents / pharmacology*
  • Insulin / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics
  • Phosphoenolpyruvate Carboxykinase (GTP) / metabolism
  • RNA, Messenger / metabolism
  • Rats, Wistar


  • Blood Glucose
  • Carbohydrates
  • Flavonoids
  • Flavonols
  • Hypoglycemic Agents
  • Insulin
  • RNA, Messenger
  • Glucose-6-Phosphatase
  • Phosphoenolpyruvate Carboxykinase (GTP)
  • Glucose
  • fisetin