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Calorie restriction effects on insulin signaling and glucose uptake in multiple insulin‐stimulated rat skeletal muscles in vivo
Author(s) -
Sharma Naveen,
Sequea Donel A,
Castorena Carlos M,
Qi Nathan,
Cartee Gregory D
Publication year - 2013
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.27.1_supplement.1202.9
Subject(s) - medicine , endocrinology , insulin , skeletal muscle , insulin receptor , glucose uptake , glucose clamp technique , calorie restriction , chemistry , insulin resistance , in vivo , phosphorylation , protein kinase b , pancreatic hormone , biology , biochemistry , microbiology and biotechnology
Calorie restriction (CR; ~60% of ad libitum, AL, food intake) has been shown to enhance whole‐body insulin sensitivity. Skeletal muscle accounts for the majority of insulin‐stimulated glucose disposal, however no previous studies have reported CR effects on both in vivo glucose uptake and insulin signaling in the same skeletal muscles. Accordingly we evaluated the effect of CR (initiated at 14‐wks of age) on the tibialis anterior (TA) and gastrocnemius (GN) muscles from 9‐mo old rats under euglycemic‐hyperinsulinemic clamp conditions. Glucose levels during the clamp were not significantly different for AL (120.7±2.7 mg/dl) versus CR (126.1±2.4 mg/dl) groups. Insulin levels during the clamp were also elevated to similar levels in AL (141.3±9.1 μU/ml) and CR (140.3±6.7 μU/ml) groups. Glucose infusion rates were 78% higher (P<0.05) in CR (31.7±1.6 mg/kg −1 × min −1 ) versus AL (17.8±0.8 mg/kg −1 × min −1 ) rats. Glucose uptake (radiolabelled 2‐deoxyglucose) was increased (P<0.05) for CR vs. AL rats in both the TA and GN. Insulin receptor Tyr1162/1163 phosphorylation was unaffected by CR in either muscle. Akt Ser473 phosphorylation was increased (P<0.05) in both muscles of CR vs. AL rats, and there was a strong trend for increased Akt Thr308 phosphorylation in CR vs. AL rats for both the TA (P=0.052) and GN (P=0.052). These results suggest that CR leads to greater whole‐body insulin sensitivity attributable at least in part to CR effects on in vivo insulin‐stimulated glucose uptake secondary to greater Akt phosphorylation in multiple muscles, including the TA and GN.