Involvement of GLUT-4 in the stimulatory effect of rutin on glucose uptake in rat soleus muscle

J Pharm Pharmacol. 2013 Aug;65(8):1179-86. doi: 10.1111/jphp.12066. Epub 2013 May 16.

Abstract

Objectives: The aim of this study was to investigate the in-vitro effect of rutin on glucose uptake in an insulin target (soleus muscle) and the mechanism of action involved.

Methods: Isolated soleus muscles from rats were treated with rutin (500 μm) with or without the following inhibitors; hydroxy-2-naphthalenylmethylphosphonic acid trisacetoxymethyl ester (HNMPA(AM)3 ), an insulin receptor tyrosine kinase activity inhibitor, wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C, colchicine, a microtubule-depolymerizing agent, PD98059, an inhibitor of mitogen-activated protein kinase kinase (MEK), and cycloheximide, an inhibitor of protein synthesis on fresh Krebs Ringer-bicarbonate plus [U-(14) C]-2-deoxy-d-glucose (0.1 μCi/ml). Samples of tissue medium were used for the radioactivity measurements.

Key findings: Rutin increased the glucose uptake in rat soleus muscle. In addition, the effect of rutin on glucose uptake was completely inhibited by pretreatment with HNMPA(AM)3 , wortmannin, RO318220, colchicine, PD98059, and cycloheximide. These results suggested that rutin stimulated glucose uptake in the rat soleus muscle via the PI3K, atypical protein kinase C and mitogen-activated protein kinase (MAPK) pathways. Also, rutin may have influenced glucose transporter translocation and may have directly activated the synthesis of the transporter GLUT-4.

Conclusion: The similarities of rutin action on glucose uptake compared with the signalling pathways of insulin constitute strong evidence for the insulin-mimetic role of rutin in glucose homeostasis.

Keywords: GLUT-4; diabetes; flavonoid; glucose uptake; rutin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Glucose / pharmacokinetics*
  • Glucose Transporter Type 4 / biosynthesis*
  • In Vitro Techniques
  • Insulin / pharmacology
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism*
  • Rats
  • Rats, Wistar
  • Rutin / pharmacology*

Substances

  • Glucose Transporter Type 4
  • Insulin
  • Slc2a4 protein, rat
  • Rutin
  • Glucose