Different role of insulin in GLUT-1 and -4 regulation in heart and skeletal muscle during perinatal hypothyroidism.
Two groups of hypothyroid rats were used; one group was given 2-mercapto-1-methylimidazole (MMI) treatment in the drinking water of the mothers and was killed at 2 and 4 days of life, and the other group was given similar MMI treatment and then was thyroidectomized at 5 days of life and killed at 8 or 20 days. Serum insulin, growth hormone (GH), and insulin-like growth factor I (IGF-I) were decreased in MMI-treated rats but increased in MMI-treated plus thyroidectomized rats. No significant reduction of thyroid hormones was observed in 2-day-old MMI rats. Protein and mRNA expression of GLUT-1 increased, and those of GLUT-4 decreased, in the heart in all populations independent of changes in insulin, GH, and IGF-I levels. However, GLUT-4 protein and mRNA expression in quadriceps and gastrocnemius skeletal muscles decreased at 4 days and increased at 8 and 20 days of life in parallel with insulin, GH, and IGF-I levels. GLUT-1 in the skeletal muscles seemed regulated posttranscriptionally and presented a decrease of mRNA expression in all stages studied. A differential sensitivity to insulin regulation of GLUT-1 and GLUT-4 glucose transporters seems to be one of the causes for the tissue-specific regulation of these glucose transporters in heart and skeletal muscles during the perinatal period.
Ramos
S
S
Instituto de Bioquímica (Centro Mixto Consejo Superior Investigaciones Científicas-Universidad Complutense de Madrid), Facultad de Farmacia, Ciudad Universitaria, 28040 Madrid, Spain.
Goya
L
L
Alvarez
C
C
Martín
M A
MA
Agote
M
M
Escrivá
F
F
Pascual-Leone
A M
AM
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D015870:Gene Expression; D005865:Gestational Age; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D013006:Growth Hormone / Q000097:blood; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008099:Liver / Q000737:chemistry; D008431:Maternal-Fetal Exchange; D008713:Methimazole / Q000008:administration & dosage; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013965:Thyroidectomy
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D008713:Methimazole; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone