Abstrakt

Restoring skeletalmuscle insulin resistance and fatty acids oxidation by AICARrescues proglycogen but notmacroglycogen pools

Hakam Alkhateeb

We examined in isolated soleusmuscle (1) the effects of palmitate-induced insulin resistance on pro-and macro-glycogen pools; and (2) the responses of these pools to rescue of insulin resistance by AICAR treatment. Incubation of soleusmuscle with palmitate (2mM) for ï‚£18 induced insulin resistance. Providing AICAR in the last 6h of incubation rescues insulin resistance. Changes in PG andMG pools, palmitate oxidation, and insulinstimulated glucose transport were examined at 0, 6,12 and 18h. Inducing insulin resistance by palmitate treatment for 18 h reduced PG pool (-62%), fatty acid oxidation (-50%), and insulin-stimulated glucose transport (-87%). However, no change was observed onMG pool. On the other hand, rectifying insulin resistance byAICAR treatment (12-18 h) fully rescued PG pool, palmitate oxidation, and insulin-stimulated glucose transport, but had no effect on MG pool. In conclusion this study demonstrates for the first time that PG pool rather thanMG pool is preferentially utilized during insulin resistance induced by prolonged incubation with palmitate.