Different role of insulin in GLUT-1 and -4 regulation in heart and skeletal muscle during perinatal hypothyroidism

Abstract

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.

Transient Congenital Hypothyroidism Alters Gene Expression of Glucose Transporters and Impairs Glucose Sensing Apparatus in Young and Aged Offspring Rats

“…Contrary to our results, higher GLUT1 mRNA expression in the heart [32, 56] and adipose tissue [25] of adult hypothyroid rats have been reported; in addition, in rats with TCH, higher GLUT1 mRNA expressions have been reported in the heart muscle at days 4 and 21 [25], and in the adipose tissue at day 4 [26] after birth.…”

“…Contrary to our results, decreased GLUT4 expression in skeletal and heart muscles[25, 56, 57] and increased GLUT4 expression in adipose tissue [25] have been reported in adult hypothyroid rats; neither are our results in agreement with previous reports in TCH rats, for skeletal and heart muscle on day 4 after birth [26] and in adipose tissue and heart muscle on day 21 after birth [25]. Additionally, no change has been reported in expression of GLUT4 in skeletal and heart muscles in rats with CH at month 3 after birth [27] or in skeletal and adipose tissue of young adults born with IUGR [58].…”

“…Our study shows that TCH in both young and aged rats is associated with lower mRNA expression of GLUT1 in all insulin-sensitive tissues, results in line with previous studies in adipocytes of adult hypothyroid rats [55] and in the skeletal muscle of 4 day old TCH rats [26]. Contrary to our results, higher GLUT1 mRNA expression in the heart [32, 56] and adipose tissue [25] of adult hypothyroid rats have been reported; in addition, in rats with TCH, higher GLUT1 mRNA expressions have been reported in the heart muscle at days 4 and 21 [25], and in the adipose tissue at day 4 [26] after birth.…”

“…Furthermore, thyroid hormones have species-specific and tissue-specific effects on GLUT1 and GLUT4 expression in insulin sensitive tissues [25, 32, 60]. During fetal life, GLUT1 is predominant in insulin sensitive tissues and transition of this dominancy to GLUT4 after birth is regulated by thyroid hormones [25, 26]. Therefore based on these results, it can be concluded that thyroid hormone deficiency during fetal life impairs normal transition of both GLUT1 and GLUT4 from fetal to adult levels in insulin sensitive tissues and can cause insulin resistance [25].…”

Decreased basal non-insulin-stimulated glucose uptake by diaphragm in streptozotocin-induced diabetic mice infected with Schistosoma mansoni

“…Skeletal muscle accounts for nearly 40% of body mass at any stage of life, and it is the main tissue involved in the insulin-induced stimulation of glucose intake (Ramos et al 2001). Glucose transport is the rate-limiting step for muscle glucose uptake during insulin-stimulated as well as basal conditions (Fueger et al 2004).…”