Nitric Oxide Increases Glucose Uptake Through a Mechanism That Is Distinct From the Insulin and Contraction Pathways in Rat Skeletal Muscle

DOI PDF PDF 10 Citations
  • Yasuki Higaki
    From the Research Division, Joslin Diabetes Center; Department of Medicine, Brigham and Women's Hospital; and Harvard Medical School, Boston,Massachusetts.
  • Michael F. Hirshman
    From the Research Division, Joslin Diabetes Center; Department of Medicine, Brigham and Women's Hospital; and Harvard Medical School, Boston,Massachusetts.
  • Nobuharu Fujii
    From the Research Division, Joslin Diabetes Center; Department of Medicine, Brigham and Women's Hospital; and Harvard Medical School, Boston,Massachusetts.
  • Laurie J. Goodyear
    From the Research Division, Joslin Diabetes Center; Department of Medicine, Brigham and Women's Hospital; and Harvard Medical School, Boston,Massachusetts.

Abstract

<jats:p>Insulin, contraction, and the nitric oxide (NO) donor, sodium nitroprusside(SNP), all increase glucose transport in skeletal muscle. Some reports suggest that NO is a critical mediator of insulin- and/or contraction-stimulated transport. To determine if the mechanism leading to NO-stimulated glucose uptake is similar to the insulin- or contraction-dependent signaling pathways,isolated soleus and extensor digitorum longus (EDL) muscles from rats were treated with various combinations of SNP (maximum 10 mmol/l), insulin (maximum 50 mU/ml), electrical stimulation to produce contractions (maximum 10 min),wortmannin (100 nmol/l), and/or the NO synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) (0.1 mmol/l). The combinations of SNP plus insulin and SNP plus contraction both had fully additive effects on 2-deoxyglucose uptake. Wortmannin completely inhibited insulinstimulated glucose transport and only slightly inhibited SNP-stimulated 2-deoxyglucose uptake, whereas L-NMMA did not inhibit contraction-stimulated 2-deoxyglucose uptake. SNP significantly increased the activity of theα1 catalytic subunit of 5′ AMP-activated protein kinase (AMPK), a signaling molecule that has been implicated in mediating glucose transport in fuel-depleted cells. Addition of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (1 mg/ml) to the drinking water of rats for 2 days failed to affect the increase in muscle 2-deoxyglucose uptake in response to treadmill exercise. These data suggest that NO stimulates glucose uptake through a mechanism that is distinct from both the insulin and contraction signaling pathways.</jats:p>

Journal

  • Diabetes

    Diabetes 50 (2), 241-247, 2001-02-01

    American Diabetes Association

Citations (10)*help

See more

Keywords

Details 詳細情報について

Report a problem

Back to top