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Myricetin, a naturally occurring flavonol, ameliorates insulin resistance induced by a high-fructose diet in rats.

Abstract
The present study was conducted to explore the effects of myricetin on insulin resistance in rats fed for 6 weeks with a diet containing 60% fructose. Repeated intravenous (i.v.) injection of myricetin (1 mg/kg per injection, 3 times daily) for 14 days was found to significantly decrease the high glucose and triglyceride levels in plasma of fructose chow-fed rats. Also, the higher degree of insulin resistance in fructose chow-fed rats as measured by homeostasis model assessment of basal insulin resistance was significantly decreased by myricetin treatment. Myricetin increased the whole-body insulin sensitivity in fructose chow-fed rats, as evidenced by the marked elevation of composite whole-body insulin sensitivity index during the oral glucose tolerance test. Myricetin was found to reverse the defect in expression of insulin receptor substrate-1 (IRS-1) and the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase) in soleus muscle of fructose chow-fed rats under the basal state, despite the protein expression of insulin receptor (IR). Increased basal phosphorylation of IR and IRS-1 as well as Akt was observed in parallel. The reduced level of insulin action on phosphorylation of IR, IRS-1 and Akt in soleus muscle of fructose chow-fed rats was reversed by myricetin treatment. Furthermore, myricetin treatment improved the defective insulin action on the translocation of glucose transporter subtype 4 (GLUT 4) in insulin-resistant soleus muscle. These findings indicate that myricetin improves insulin sensitivity through the enhancement of insulin action on IRS-1-associated PI 3-kinase and GLUT 4 activity in soleus muscles of animals exhibiting insulin resistance.
AuthorsI-Min Liu, Thing-Fong Tzeng, Shorong-Shii Liou, Ting-Wei Lan
JournalLife sciences (Life Sci) Vol. 81 Issue 21-22 Pg. 1479-88 (Nov 10 2007) ISSN: 0024-3205 [Print] Netherlands
PMID17976658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Blood Glucose
  • Flavonoids
  • Flavonols
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Insulin
  • Thiazolidinediones
  • Triglycerides
  • Rosiglitazone
  • Fructose
  • myricetin
  • Glycogen
  • Cholesterol
  • Phosphatidylinositol 3-Kinases
  • Receptor, Insulin
Topics
  • Animals
  • Blood Glucose (metabolism)
  • Blotting, Western
  • Cholesterol (blood)
  • Diet (adverse effects)
  • Electrophoresis, Polyacrylamide Gel
  • Flavonoids (pharmacology)
  • Flavonols (pharmacology)
  • Fructose (pharmacology)
  • Glucose Transporter Type 4 (metabolism)
  • Glycogen (biosynthesis)
  • Hepatocytes (drug effects, metabolism)
  • Hypoglycemic Agents (pharmacology)
  • Immunoprecipitation
  • Insulin (blood)
  • Insulin Resistance (physiology)
  • Male
  • Muscle, Skeletal (drug effects)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Phosphorylation
  • Rats
  • Rats, Wistar
  • Receptor, Insulin (drug effects)
  • Rosiglitazone
  • Thiazolidinediones (pharmacology)
  • Triglycerides (blood)

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