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Effects of Calorie Restriction and Fiber Type on Glucose Uptake in Single Fibers from Old Rats
Author(s) -
Wang Haiyan,
Arias Edward B.,
Yu Carmen S.,
Verkerke Anthony R.P.,
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.lb722
Subject(s) - glucose uptake , medicine , skeletal muscle , calorie restriction , endocrinology , insulin , fiber , adipose tissue , chemistry , myosin , biology , biochemistry , organic chemistry
The major tissue for insulin‐stimulated glucose disposal is skeletal muscle. Calorie restriction (CR; reducing calorie intake by ~40% below ad libitum) can increase glucose uptake by insulin‐stimulated muscle. Skeletal muscle is comprised of multiple, heterogeneous fiber types, and the efficacy of CR for enhancing insulin‐stimulated glucose uptake across all fiber types is uncertain. The conventional approach to evaluate possible fiber type differences has been to measure glucose uptake by multiple muscles or regions of muscles with differing fiber type profiles. However, tissue analyses cannot resolve fiber type differences in glucose uptake at the cellular level because: 1) whole muscles include multiple fiber types; 2) apparently no rodent muscle has been identified that is mostly comprised of type IIX fibers; 3) measurement of glucose uptake by fibers expressing multiple myosin heavy chain isoforms (i.e., hybrid fibers) requires single fiber analysis; and 4) various cell types (including neural, vascular, and adipose cells) contribute to glucose uptake determined in muscle tissue samples. The limitations of muscle tissue analysis motivated us to recently develop and validate the first method to determine both glucose uptake and fiber type in a single rat skeletal muscle fiber. We used this method in the current study with the primary aim to determine in 23–26 months‐old rats the effects of chronic CR (60% of ad libitum, AL, initiated at 14 weeks‐old) and fiber type on insulin‐stimulated glucose uptake by single fibers of diverse fiber types. Isolated epitrochlearis muscles from AL and CR rats were incubated with [ 3 H]‐2‐deoxyglucose ± 1.8nMinsulin. Glucose uptake and fiber type (based on myosin heavy chain expression) were determined for single fibers dissected from the muscles. We also determined CR‐effects on the abundance of hexokinase II (a key enzyme that favors greater glucose uptake by catalyzing the conversion of glucose to glucose 6‐phosphate) in single fibers by immunoblotting. We found in single fibers from CR compared to AL rats: 1) significantly greater insulin‐stimulated glucose uptake by type I, IIA, IIB, IIBX and IIX fibers (P<0.01 for I, IIA and IIB; P<0.001 for IIBX and IIX); and 2) unaltered hexokinase II abundance in each fiber type. These observations revealed at the cellular level that long‐term CR by older rats enhanced insulin‐stimulated glucose uptake in rat epitrochlearis muscle regardless of fiber type and independent of elevated hexokinase II protein content. Support or Funding Information This work was supported by a grant from the National Institute on Aging at the National Institutes of Health (grant number AG10026) to GDC.