Strain-Dependent Differences for Suppression of Insulin-Stimulated Glucose Uptake in Skeletal and Cardiac Muscle by Ethanol

Authors

  • Charles H. Lang,

    Corresponding author
    1. Department of Cellular and Molecular Physiology, and Surgery, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
    • Reprint requests: Charles H. Lang, PhD, Department of Cellular and Molecular Physiology, and Surgery, The Pennsylvania State University College of Medicine, Hershey, PA 17033; Tel.: 717-531-5538; Fax: 717-531-7667; E-mail: clang@psu.edu

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  • Zoltan Derdak,

    1. Division of Gastroenterology and Liver Research Center, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island
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  • Jack R. Wands

    1. Division of Gastroenterology and Liver Research Center, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island
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Abstract

Background

Chronic ethanol (EtOH) consumption impairs the ability of insulin to suppress hepatic glucose production in a strain-dependent manner, with hepatic insulin resistance being greater in Long–Evans (LE) than Sprague–Dawley (SD) rats. We assessed whether strain differences exist for whole-body and tissue glucose uptake under basal and insulin-stimulated conditions and whether they were associated with coordinate strain-dependent elevations in muscle cytokines.

Methods

Male rats (160 g) were provided the Lieber-DeCarli EtOH-containing (36% total energy) diet or pair-fed a control diet for 8 weeks. Rats were studied in the basal state or during a euglycemic hyperinsulinemic clamp, and whole-body glucose flux assessed using 3H-glucose and in vivo tissue glucose uptake by 14C-2-deoxyglucose.

Results

EtOH impaired whole-body insulin-mediated glucose uptake (IMGU) more in SD than LE rats. This difference was due to impaired IMGU by gastrocnemius and heart in EtOH-fed SD versus LE rats. However, decreased IMGU in adipose tissue (epididymal and perirenal) produced by EtOH was comparable between strains. EtOH-induced insulin resistance in muscle from SD rats was associated with reduced AKT and AS160 phosphorylation and plasma membrane-localized GLUT4 protein as well as enhanced phosphorylation of c-Jun N-terminal kinase (JNK) and IRS-1 (S307), changes which were absent in muscle from LE rats. EtOH increased tumor necrosis factor alpha (TNFα) mRNA in gastrocnemius and fat under basal conditions in both SD and LE rats; however, hyperinsulinemia decreased TNFα in skeletal muscle from LE, but not SD rats. Interleukin (IL)-6 mRNA in gastrocnemius was increased under basal conditions and increased further in response to insulin in SD rats, but no EtOH- or insulin-induced change was detected in muscle IL-6 of LE rats.

Conclusions

These data indicate strain-dependent differences in EtOH-induced IMGU in skeletal and cardiac muscle, but not fat, associated with sustained increases in TNFα and IL-6 mRNA and JNK activation and decreased plasma membrane GLUT4 in response to insulin.

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