Enzogenol improves diabetes-related metabolic change in C57BL/KsJ-db/db mice, a model of type 2 diabetes mellitus

J Pharm Pharmacol. 2014 Jun;66(6):875-85. doi: 10.1111/jphp.12211. Epub 2014 Feb 24.

Abstract

Objectives: Dietary use of pine bark extract has been associated with reduced risk of inflammation and diabetes. In this study, we investigated the antidiabetic effects of enzogenol, proanthocyanidins-rich bioflavonoid extract derived from the pine bark of New Zealand Pinus radiata trees, using C57BL/KsJ-db/db mice.

Methods: After 1-week acclimation period, the db/db mice were divided into vehicle-treated, Enzogenol-treated (12.5, 25 and 50 mg/kg; EZ) and positive control (tea polyphenol 50 mg/kg; TPP) groups.

Key findings: The administration of EZ improved the glucose tolerance and lowered the glycosylated haemoglobin (HbA1C ), insulin and glucagon levels in blood. Interestingly, EZ and TPP treatments resulted in reduced hepatic free fatty acid, cholesterol and triglyceride levels in db/db mice. EZ and TPP treatments significantly elevated hepatic AMPK activity, and the expression of proteins related to glucose homeostasis and lipid metabolism, such as glucokinase, peroxisome proliferator-activated receptor (PPAR)α and long-chain acyl-CoA dehydrogenase protein level with a simultaneous reduction of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase protein expression. In addition, the EZ administration groups had an increased hepatic glycogen synthase expression in db/db mice.

Conclusions: These results suggest that EZ may be beneficial in improving insulin resistance and hyperglycaemia in type 2 diabetic mice by enhancing the glucose and lipids metabolism.

Keywords: Enzogenol; gluconeogenesis; glucose homeostasis; insulin resistance; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Flavonoids / therapeutic use*
  • Glucagon / blood
  • Glucose / metabolism
  • Glucose Tolerance Test
  • Glycated Hemoglobin / analysis
  • Insulin / blood
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Quercetin / analogs & derivatives*
  • Quercetin / therapeutic use

Substances

  • Flavonoids
  • Glycated Hemoglobin A
  • Insulin
  • enzogenol
  • hemoglobin A1c protein, human
  • Glucagon
  • Quercetin
  • Glucose