A Novel Xanthene Derivative, DS20060511, Attenuates Glucose Intolerance by Inducing Skeletal Muscle-specific GLUT4 Translocation in Diabetic Mice [post]

Shinji Furuzono, Tetsuya Kubota, Junki Taura, Masahiro Konishi, Asuka Naito, Hiroshi Karasawa, Naoto Kubota, Takashi Kadowaki
2020 unpublished
Reduced glucose uptake into the skeletal muscle is an important pathophysiological abnormality in type 2 diabetes, and is caused by impaired translocation of glucose transporter 4 (GLUT4) to the skeletal muscle cell surface. We found a novel xanthene compound, DS20060511, which induces GLUT4 translocation to the skeletal muscle cell surface, thereby stimulating glucose uptake into the skeletal muscle. DS20060511 induced GLUT4 translocation and glucose uptake into differentiated L6-miytubes and
more » ... ed L6-miytubes and into the skeletal muscles of live mice. These effects were completely abolished in GLUT4 knockout mice. Induction of GLUT4 surface translocation by DS20060511 was independent of the insulin signaling pathways including IRS1-Akt-AS160 phosphorylation and IRS1-Rac1-actin polymerization, eNOS pathway and AMPK pathway. Acute and chronic DS20060511 treatment attenuated the glucose intolerance in obese diabetic mice. Taken together, DS20060511 acts as a skeletal muscle specific-GLUT4 translocation enhancer to facilitate glucose utilization. Further studies with DS20060511 would help to develop a novel antidiabetic medicine.
doi:10.21203/rs.3.rs-84209/v1 fatcat:lzrhwcc7frhwxefhb4wf42nfci