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Prior Treatment with the AMPK Activator AICAR Induces Subsequently Enhanced Glucose Uptake in Isolated Skeletal Muscles from Old Rats
Author(s) -
Oki Kentaro,
Arias Edward B,
Cartee Gregory D
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb726
Subject(s) - medicine , endocrinology , insulin , ampk , skeletal muscle , incubation , glucose uptake , activator (genetics) , chemistry , protein kinase a , kinase , biochemistry , receptor
Prior treatment of isolated skeletal muscles from young rats (≤4 months‐old) to the 5′ adenosine monophosphate‐activated protein kinase (AMPK) activator 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR) in the presence of serum can induce elevated insulin‐stimulated glucose uptake (GU) several hours after of removal of the muscles from AICAR and serum. Previous research did not determine if both AICAR and serum were required for the observed effect on insulin‐dependent GU, or if incubation with either was sufficient. Earlier research also has not evaluated the effects of prior AICAR incubation with and without serum on the GU of muscles from older rats. Accordingly, we examined the separate and combined effects of AICAR and serum on subsequent insulin‐independent and insulin‐dependent GU in skeletal muscles from aged rats (23–24 month old; n=20). Both epitrochlearis muscles from each rat were dissected and split into two separate muscle strips. Each muscle strip underwent a four‐step incubation. During step 1 (60 minutes), one muscle strip from each animal was incubated with: Krebs‐Henseleit Buffer (KHB) alone, KHB with AICAR, serum alone, or serum with AICAR. During step 2 (180 minutes), all muscle strips were incubated with KHB. During steps 3 (30 minutes) and 4 (20 minutes), all 4 strips from 10 rats were incubated without insulin, and all 4 strips from the remaining 10 rats were incubated with insulin. During step 4, muscle strips were incubated with radiolabeled 3‐O‐methyl‐D‐glucose and the same insulin concentration as the previous step. Repeated measures analysis of variance (RM ANOVA) in the basal (no insulin) group indicated a significant interaction (serum × AICAR) for insulin‐independent GU. In the insulin group, RM ANOVA revealed a significant main effect of AICAR on insulin‐dependent GU without a significant main effect of serum or significant serum × AICAR interaction. Our working hypothesis is that the elevated insulin‐independent GU after combined AICAR and serum incubation is secondary to subsequently elevated phosphorylation of TBC1D1 on Ser237 (an AMPK‐phosphosite), and the AICAR‐induced elevation of insulin‐dependent GU is secondary to subsequently elevated phosphorylation of TBC1D4 on Ser711 (an AMPK phosphosite) and Thr642 (an Akt‐phosphosite). Support or Funding Information NIA Training Grant AG 000114 and NIA R01 AG10026 (GDC)