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Selective chronic regulation of GLUT1 and GLUT4 content by insulin, glucose, and lipid in rat cardiac muscle in vivo


The glucose transporter GLUT1 may play a more important role in cardiac than in skeletal muscle, but its regulation is unclear. During fasting, cardiac GLUT1 declines in the presence of low plasma insulin and glucose and high nonesterified fatty acid (NEFA) levels, whereas GLUT4 is unchanged. We investigated insulin, glucose, and NEFA levels as regulatory factors of cardiac GLUT content in chronically cannulated rats. Fasting rats were infused for 24 h with saline or insulin (2 rates) while plasma glucose was equalized by a glucose clamp; final transporter content was compared with a fed control group. There was a close association of GLUT1 content with insulin (r2 = 0.83, P < 0.001), with GLUT1 varying over a threefold range, under equivalent fasting glycemic conditions (plasma glucose, 5.1 +/- 0.1 mM). Maintenance of fed insulin levels during fasting prevented the GLUT1 fall (P < 0.01), whereas hyperinsulinemia (117 +/- 10 mU/l) led to significant overexpression of GLUT1 (155 +/- 12% of control, P < 0.01). When high glucose (7.6 +/- 0.1 mM) or high NEFA (0.76 +/- 0.05 mM) levels accompanied the hyperinsulinemia, upregulation of GLUT1 was blocked. GLUT1 content correlated with an estimate of cardiac glucose clearance across the groups. Cardiac GLUT4 content, hexokinase, and acyl-CoA synthase activities were unaffected by fasting, insulin, or substrate manipulation. In conclusion, insulin preferentially upregulates GLUT1 (but not GLUT4) in a dose-dependent manner in cardiac muscle in vivo, and substrate supply modulates this response, since upregulation can be effectively blocked by increased glucose or lipid availability. Therefore, both insulin exposure and energy status of cardiac muscle may be important determinants of cardiac GLUT1 expression.

Type Journal
ISBN 0002-9513 (Print)
Authors Laybutt, D. R.;Thompson, A. L.;Cooney, G. J.;Kraegen, E. W. :
Publisher Name Am J Physiol
Published Date 1997-01-01
Published Volume 273
Published Issue 3 Pt 2
Published Pages H1309-16
Status Published in-print
URL link to publisher's version