Open AccessRapid Reversal of Insulin-Stimulated AS160 Phosphorylation in Rat Skeletal Muscle after Insulin Exposure
Author(s) -
Naveen Sharma,
Edward B. Arias,
Gregory D. Cartee
Publication year - 2010
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931707
Subject(s) - insulin , medicine , endocrinology , protein kinase b , phosphorylation , skeletal muscle , glucose uptake , chemistry , insulin receptor , pancreatic hormone , biology , insulin resistance , biochemistry
Increased phosphorylation of Akt substrate of 160 kDa (AS160) isessential to trigger the full increase in insulin-stimulated glucosetransport in skeletal muscle. The primary aim of this study was tocharacterize the time course for reversal of insulin-stimulatedAS160 phosphorylation in rat skeletal muscle after insulinremoval. The time courses for reversal of insulin effects bothupstream (Akt phosphorylation) and downstream (glucoseuptake) of AS160 were also determined. Epitrochlearis muscleswere incubated in vitro using three protocols which differed withregard to insulin exposure: No Insulin (never exposed to insulin),Transient Insulin (30 min with 1.8 nmol/l insulin, then incubationwithout insulin for 10, 20 or 40 min), or Sustained Insulin(continuously incubated with 1.8 nmol/l insulin). After removal ofmuscles from insulin, Akt and AS160 phosphorylation reversedrapidly, each with a half-time of <10 min and essentially fullreversal by 20 min. Glucose uptake reversed more slowly (halftime between 10 and 20 min with essentially full reversal by40 min). Removal of muscles from insulin resulted in a rapidreversal of the increase in AS160 phosphorylation whichpreceded the reversal of the increase in glucose uptake,consistent with AS160 phosphorylation being essential formaintenance of insulin-stimulated glucose uptake.