Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives

Abstract

Some of inositol derivatives have been reported to help the action of insulin stimulating glucose uptake in skeletal muscle cells. Rat L6 myotubes were employed in an attempt to develop an in vitro model system for investigation of the possible insulin-like effect of eight inositol derivatives, namely allo-inositol, D-chiro-inositol L-chiro-inositol, epi-inositol, muco-inositol, myo-inositol, scyllo-inositol and D-pinitol. At a higher concentration of 1 mM seven inositol derivatives other than myo-inositol were able to stimulate glucose uptake, while at 0.1 mM only D-chiro-inositol, L-chiro-inositol, epiinositol and muco-inositol could induce glucose uptake, indicating their significant insulin-mimetic activity. Immunoblot analyses revealed that at least Dchiro-inositol, L-chiro-inositol, epi-inositol, mucoinositol and D-pinitol were able to induce translocation of glucose transporter 4 (GLUT4) to plasma membrane not only in L6 myotubes but also in skeletal muscles of rats ex vivo. These results demonstrated that L6 myotubes appeared efficient as an in vitro system to identify inositol derivatives exerting an insulin-like effect on muscle cells depending on the induced translocation of GLUT4.

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

“…[163] At a concentration of 0.1mM L-chiro-inositol is as efficient as 100nM insulin in promoting GLUT4-dependent glucose uptake by rat L6 myotubes. [48] Between nondiabetics and noninsulin-dependent diabetics there was little difference in the urinary excretion of L-chiroinositol, but excretion increased just over three-fold, to 0.51 μmol/day, in insulin-dependent diabetics. [107] The non-mammalian biology of L-chiro-inositol is discussed in the Supporting Information (SI_2).…”

“…[122] The uptake of insulin by rat L6 myotubes is stimulated by 1D-chiro-, 1L-chiro-, epi-and muco-inositol and may be associated with the translocation of the glucose transporter 4 protein to the plasma membrane: allo-and scyllo-inositols are less potent stimulants. [48] Intrauterine growth restriction in piglets results in low weight at birth. These low weight piglets have significantly higher plasma concentrations of myo-inositol and D-chiro-inositol than their larger littermates.…”

“…[40] At a concentration of 0.1mM epi-inositol is as efficient as 100nM insulin in promoting GLUT4-dependent glucose uptake by rat L6 myotubes. [48] epi-Inositol has an initial impact on the aggregation of amyloid-β associated with Alzheimer's disease but is unable to maintain that impact over time. [64] The non-mammalian biology of epi-inositol is discussed in the Supporting Information (SI_2).…”

“…[48] L-myo-Inositol-1-phosphate synthase isolated from human fetal brain and adult rat brain is able to catalyse the conversion of galactose 6-phosphate to muco-inositol 1-phosphate. [198] Whether this reaction occurs in vivo is unknown.…”

“…[48] It is not known, for either of these activities, if one particular conformational isomer evokes these effects.…”