Decreased GLUT-4 mRNA content and insulin-sensitive deoxyglucose uptake show insulin resistance in the hypertensive rat heart.
OBJECTIVE
Insulin resistance in skeletal muscle and adipose tissue often accompanies hypertension; however, it has not been shown that heart muscle is similarly affected. The aims of this study were to determine whether basal and insulin-stimulated glucose transport and glucose transporter mRNA content are altered in the spontaneously hypertensive rat (SHR) heart.


METHODS
Hearts from 16-18-month-old SHRs were compared to their normotensive (WKY) controls. The accumulation of 2-deoxyglucose-6-phosphate (2DG6P), detected using 31P nuclear magnetic resonance spectroscopy, was used to assess glucose uptake before and during insulin stimulation in the isolated perfused heart. The mRNA levels of both the insulin-sensitive glucose transporter (GLUT-4) and the transporter responsible for basal glucose uptake (GLUT-1) were quantified by Northern blot analysis.


RESULTS
The hypertensive rat hearts exhibited hypertrophy in that the heart/body weight ratio was increased by 59%. In these hearts, the basal rate of glucose uptake was 3-fold greater and hexokinase activity was 1.6 fold greater than that of the control rat hearts. On exposure to insulin, accumulation of 2DG6P increased 5-fold in the control hearts, but only 1.4-fold in the SHR hearts. Thus, in the presence of insulin, the rate of glucose uptake by the hypertensive rat heart was significantly (P < 0.05) reduced, being 82% of control. GLUT-4 mRNA content was decreased was no significant difference in the GLUT-1 mRNA content.


CONCLUSIONS
We have demonstrated insulin resistance in the hypertrophied heart of the hypertensive rat that may have a molecular basis in a lower GLUT-4 content.
Paternostro
G
G
Department of Biochemistry, University of Oxford, UK.
Clarke
K
K
Heath
J
J
Seymour
A M
AM
Radda
G K
GK
D000818:Animals; D015152:Blotting, Northern; D006332:Cardiomegaly / Q000378:metabolism; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000032:analysis / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010477:Perfusion; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D005958:Glucosephosphates; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; C015785:2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate