Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin-cadmium induced diabetic nephrotoxic rats

Toxicol Appl Pharmacol. 2014 Sep 1;279(2):173-85. doi: 10.1016/j.taap.2014.05.014. Epub 2014 Jun 9.


Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ-Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ-Cd induced diabetic nephrotoxic rats.

Keywords: Glucose metabolism; Glucose transporters; Insulin signaling; Myricetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / enzymology
  • Albuminuria / prevention & control
  • Animals
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Blood Urea Nitrogen
  • Cadmium Chloride*
  • Carbohydrate Metabolism / drug effects*
  • Creatinine / blood
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / chemically induced
  • Diabetic Nephropathies / enzymology
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / prevention & control*
  • Enzymes / metabolism*
  • Flavonoids / pharmacology*
  • Glycated Hemoglobin A / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Insulin / blood*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / physiopathology
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Urea / blood
  • Uric Acid / blood


  • Biomarkers
  • Blood Glucose
  • Enzymes
  • Flavonoids
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Uric Acid
  • myricetin
  • Urea
  • Creatinine
  • Cadmium Chloride