In an attempt to develop new substances for treating
insulin resistance, obese Zucker rats were employed to screen the effect of
myricetin, an active principle of Abelmoschus moschatus (Malvaceae), on
insulin resistance.
Myricetin purified from the aerial portion of the plant was administered intravenously ( I. V.) into animals. A dose-dependent decrease in the plasma
glucose concentration of obese Zucker rats was observed 30 min following an I. V. injection. Moreover, repeated I. V. injection of
myricetin (1 mg/kg) into obese Zucker rats 3 times daily for 1 week reduced the value of the
glucose-
insulin index, an index of
insulin resistance calculated from the areas under the curve of
glucose and
insulin during the intraperitoneal
glucose tolerance test. Additionally, repeated
myricetin treatments overturned the inability of
insulin to increase the expression of
glucose transporter subtype 4 (GLUT 4) and to increase the
protein levels and phosphorylation of
insulin receptor substrate-1 (IRS-1) in soleus muscle of these obese rats. The inability of
insulin to increase expression of the p85 regulatory subunit of
phosphatidylinositol 3-kinase (PI3-kinase) and to promote Akt
serine phosphorylation in soleus muscle of these rats were also overturned by repeated
myricetin treatments. These findings indicate that
myricetin improves
insulin sensitivity through increased post-
receptor insulin signaling mediated by enhancements in IRS-1-associated
PI3-kinase and GLUT 4 activity in muscles of obese Zucker rats.
Myricetin might be used as a model substance for the development of
antidiabetic compounds.