Myricetin, a naturally occurring flavonol, ameliorates insulin resistance induced by a high-fructose diet in rats.
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.
Liu
I-Min
IM
Department of Pharmacy, Tajen University, Yen-Pou, Ping Tung Shien, Taiwan, ROC. iml@mail.tajen.edu.tw
Tzeng
Thing-Fong
TF
Liou
Shorong-Shii
SS
Lan
Ting-Wei
TW
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D004032:Diet / Q000009:adverse effects*; D004591:Electrophoresis, Polyacrylamide Gel; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols / Q000494:pharmacology*; D005632:Fructose / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D047468:Immunoprecipitation; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005419:Flavonoids; D044948:Flavonols; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D005632:Fructose; C040015:myricetin; D006003:Glycogen; D002784:Cholesterol; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin