Keywords: Glycogen synthase kinase-3, GSK-3 inhibitors
From dietary glucose to liver glycogen: the full circle round.
Schematic diagram of the inolvementof hte insulin signaling pathway in the regulation of glucosetransport and glycogen synthesis. Insulin binds to itstransmembrane receptor, insulin receptor (IR), and promotes itsautophosphorylation at tyrosine residues (p-IR). Activated p-IRrecruits IR substrate (IRS) and enhances its activation bymediating its phosphorylation (p-IRS). p-IRS subsequently binds top85, the regulatory subunit of phosphoinositide-3 kinase (PI3K),and elevates the activation of its catalytic subunit p110, whichsubsequently activates phosphoinositide-dependent kinase (PDK). Asthe upstream kinase of Akt, PDK promotes the phosphorylation of Akt(p-Akt) at Thr308 and Ser473. Activated Akt regulates glucosemetabolism in two pathways. One is promoting glucose transporterGLUT translocation from the cytoplasm to the membrane, whichmediates glucose uptake; another one is repressing the function ofglycogen synthesis kinase 3 (GSK3) by enhancing its phosphorylationat Ser9, and then enhancing the activation of GS and promotingglycogen synthesis.
On the measurement of pathways of glycogen synthesis.
It has been suggested that the initial elevated replacement rate is insulin INdependent, while the slowing at 4 hours is a shift back towards the normal insulin dependent muscle cell uptake rate.After this initial 4 hours surge, muscle glycogen stores are replenished at a rate of approximately 5% per hour.