Insulin-Mediated Hemodynamic Changes Are Impaired in Muscle of Zucker Obese Rats

  1. Michelle G. Wallis12,
  2. Catherine M. Wheatley1,
  3. Stephen Rattigan1,
  4. Eugene J. Barrett2,
  5. Andrew D.H. Clark1 and
  6. Michael G. Clark1
  1. 1Department of Biochemistry, University of Tasmania, Hobart, Tasmania, Australia
  2. 2Health Sciences Center, University of Virginia, Charlottesville, Virginia


    Insulin-mediated hemodynamic effects in muscle were assessed in relation to insulin resistance in obese and lean Zucker rats. Whole-body glucose infusion rate (GIR), femoral blood flow (FBF), hindleg glucose extraction (HGE), hindleg glucose uptake (HGU), 2-deoxyglucose (DG) uptake into muscles of the lower leg (Rg), and metabolism of infused 1-methylxanthine (1-MX) to measure capillary recruitment were determined for isogylcemic (4.8 ± 0.2 mmol/l, lean; 11.7 ± 0.6 mmol/l, obese) insulin-clamped (20 mU · min−1 · kg−1 × 2 h) and saline-infused control anesthetized age-matched (20 weeks) lean and obese animals. Obese rats (445 ± 5 g) were less responsive to insulin than lean animals (322 ± 4 g) for GIR (7.7 ± 1.4 vs. 22.2 ± 1.1 mg · min−1 · kg−1, respectively), and when compared with saline-infused controls there was no increase due to insulin by obese rats in FBF, HGE, HGU, and Rg of soleus, plantaris, red gastrocnemius, white gastrocnemius, extensor digitorum longus (EDL), or tibialis muscles. In contrast, lean animals showed marked increases due to insulin in FBF (5.3-fold), HGE (5-fold), HGU (8-fold), and Rg (∼5.6-fold). Basal (saline) hindleg 1-MX metabolism was 1.5-fold higher in lean than in obese Zucker rats, and insulin increased in only that of the lean. Hindleg 1-MX metabolism in the obese decreased slightly in response to insulin, thus postinsulin lean was 2.6-fold that of the postinsulin obese. We conclude that muscle insulin resistance of obese Zucker rats is accompanied by impaired hemodynamic responses to insulin, including capillary recruitment and FBF.


    • Address correspondence and reprint requests to Prof. Michael G. Clark, Biochemistry, Medical School, University of Tasmania, GPO Box 252–58, Hobart, 7001 TAS, Australia. E-mail: michael.clark{at}

      Received for publication 23 April 2002 and accepted in revised form 19 August 2002.

      EDL, extensor digitorum longus; ELISA, enzyme-linked immunosorbent assay; FBF, femoral blood flow; GIR, glucose infusion rate; HGE, hindleg glucose extraction; HGU, hindleg glucose uptake; IRS, insulin receptor substrate; NO, nitric oxide; PI, phosphatidylinositol; Rg, rate of glucose uptake; TNFα, tumor necrosis factor-α; VSMC, vascular smooth muscle cell; 1-MX, 1-methylxanthine; 2-DG, 2-deoxyglucose.

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