Dr. Laybutt et al., SELECTIVE CHRONIC REGULATION OF GLUT1 AND GLUT4 CONTENT BY INSULIN, GLUCOSE, AND LIPID IN RAT CARDIAC-MUSCLE IN-VIVO, American journal of physiology. Heart and circulatory physiology, 42(3), 1997, pp. 1309-1316
The glucose transporter GLUT1 may play a more important role in cardia
c than in skeletal muscle, but its regulation is unclear. During fasti
ng, cardiac GLUT1 declines in the presence of low plasma insulin and g
lucose and high nonesterified fatty acid (NEFA) levels, whereas GLUT4
is unchanged. We investigated insulin, glucose, and NEFA levels as reg
ulatory 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 transport
er content was compared with a fed control group. There was a close as
sociation of GLUT1 content with insulin (r(2) = 0.83, P < 0.001), with
GLUT1 varying over a threefold range, under equivalent fasting glycem
ic conditions (plasma glucose, 5.1 +/- 0.1 mM). Maintenance of fed ins
ulin levels during fasting prevented the GLUT1 fall (P < 0.01), wherea
s 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 hype
rinsulinemia, upregulation of GLUT1 was blocked. GLUT1 content correla
ted with an estimate of cardiac glucose clearance across the groups. C
ardiac GLUT4 content, hexokinase, and acyl-CoA synthase activities wer
e unaffected by fasting, insulin, or substrate manipulation. In conclu
sion, insulin preferentially upregulates GLUT1 (but not GLUT4) in a do
se-dependent manner in cardiac muscle in vivo, and substrate supply mo
dulates this response, since upregulation can be effectively blocked b
y increased glucose or lipid availability. Therefore, both insulin exp
osure and energy status of cardiac muscle may be important determinant
s of cardiac GLUT1 expression.