Antidiabetic Effect of Taxifolin in Cultured L6 Myotubes and Type 2 Diabetic Model KK-Ay/Ta Mice with Hyperglycemia and Hyperuricemia.

Abstract

Muscle is the largest tissue in our body and plays an important role in glucose homeostasis and hence diabetes. In the present study, we examined the effects of taxifolin (TXF) on glucose metabolism in cultured L6 muscle cells (myotubes) and in type 2 diabetic (T2D) model KK-Ay/Ta mice. TXF dose-dependently increased glucose uptake (GU) in L6 myotubes under the condition of insulin absence. This increase in GU was partially, but significantly canceled by TXF treatment in combination with either LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), which phosphorylates protein kinase B (Akt) or Compound C, an inhibitor of 5'-adenosine monophosphate-activated protein kinase (AMPK). Furthermore, TXF was demonstrated to activate (=phosphorylate) both Akt and AMPK, and promote glucose transporter 4 (GLUT4) translocation to the plasma membrane from cytosol of L6 myotubes via both PI3K/Akt and AMPK signaling pathways. Based on these in vitro findings, we conducted an in vivo experiment in KK-Ay/Ta mice with hyperglycemia and hyperuricemia. Fasting plasma glucose, insulin, uric acid levels and an index of insulin resistance (HOMA-IR) increased significantly in the T2D model mice compared with normal ones. Such rises in the T2D state were significantly suppressed by oral administration of TXF for four weeks. These results suggest that TXF is a potent antihyperglycemic and antihyperuricemic phytochemical in the T2D state.

• Authors: Shinji Kondo, Shin-Ichi Adachi, Fumiaki Yoshizawa, Kazumi Yagasaki
• Journal: Current issues in molecular biology (Curr Issues Mol Biol) Vol. 43 Issue 3 Pg. 1293-1306 (Sep 26 2021) ISSN: 1467-3045 [Electronic] Switzerland
• PMID: 34698101 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Glucose Transporter Type 4
• Hypoglycemic Agents
• Lipids
• Quercetin
• taxifolin
• Proto-Oncogene Proteins c-akt
• AMP-Activated Protein Kinases
• Glucose

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Blood Glucose (drug effects)
• Body Weight (drug effects)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Glucose (metabolism)
• Glucose Transporter Type 4 (metabolism)
• Hyperglycemia (drug therapy, etiology, metabolism)
• Hyperuricemia (drug therapy, etiology, metabolism)
• Hypoglycemic Agents (chemistry, pharmacology)
• Lipids (blood)
• Male
• Mice
• Muscle Fibers, Skeletal (drug effects, metabolism)
• Phosphorylation (drug effects)
• Protein Transport
• Proto-Oncogene Proteins c-akt (metabolism)
• Quercetin (analogs & derivatives, chemistry, pharmacology)
• Signal Transduction (drug effects)