ABSTRACT
BACKGROUND/AIMS: Transient congenital hypothyroidism (TCH) could disturb carbohydrate metabolism in adulthood. Aging is associated with increased risk of type 2 diabetes. This study aims to address effects of TCH on mRNA expressions of glucose transporters (GLUTs) and glucokinase (GcK) in islets and insulin target tissues of aged offspring rats. METHODS: The TCH group received water containing 0.025% 6-propyl-2-thiouracil during gestation. Offspring from control and TCH groups (n=6 in each group) were followed until month 19. Gene expressions of GLUTs and GcK were measured at months 3 and 19. RESULTS: Compared to controls, aged TCH rats had higher GLUT4 expression in heart (4.88 fold) and soleus (6.91 fold), while expression was lower in epididymal fat (12%). In TCH rats, GLUT2 and GcK expressions in islets were lower in young (12% and 10%, respectively) and higher in aged (10.85 and 8.42 fold, respectively) rats. In addition, liver GLUT2 and GcK expressions were higher in young (13.11 and 21.15 fold, respectively) and lower in aged rats (44% and 5%, respectively). CONCLUSION: Thyroid hormone deficiency during fetal period impaired glucose sensing apparatus and changed glucose transporter expression in insulin-sensitive tissues of aged offspring rats. These changes may contribute to impaired carbohydrate metabolism.
Subject(s)
Aging , Congenital Hypothyroidism/pathology , Glucose Transporter Type 1/metabolism , Glucose Transporter Type 2/metabolism , Glucose Transporter Type 4/metabolism , Animals , Blood Glucose/analysis , Body Weight , Congenital Hypothyroidism/metabolism , Congenital Hypothyroidism/veterinary , Glucokinase/genetics , Glucokinase/metabolism , Glucose Tolerance Test , Glucose Transporter Type 1/genetics , Glucose Transporter Type 2/genetics , Glucose Transporter Type 4/genetics , Insulin/analysis , Islets of Langerhans/metabolism , Liver/metabolism , Male , Myocardium/metabolism , RNA, Messenger/metabolism , Rats , Rats, Wistar , Thyrotropin/blood , Thyroxine/blood , Transcriptome , Triiodothyronine/bloodABSTRACT
OBJECTIVES: Some pathologic situations such as diabetes and metabolic syndrome are associated with alternation in nitric oxide level. Incidence of these condition increases with aging. On the other hand, insulin secretion is modulated by nitric oxide, and nitric oxide synthase (NOS) activity is also altered in diabetes. In this study, modification in the enzyme activity associated with aging and also optimized procedure for islet NOS assay was investigated. MATERIALS AND METHODS: Male Wistar rats were randomly divided in two experimental groups: A: adult rats; were 4 month old and B: old rats; were 12 month old. In all groups, plasma glucose, insulin and NOX (nitrite + nitrate = NOX) were measured, and also insulin secretion in isolated pancreatic islet with or without L-NAME was investigated. Furthermore, the inducible NOS activity with L-citrulline measurement in islets was measured. RESULTS: L-citrulline was quantified using one step HPLC column. Aging induced hyperglycemia (P<0.05) and excess plasma NOX (17.74 ± 1.664 and 26.25 ± 2.166 µmol/l in A and B groups respectively, P<0.05) with unaltered plasma insulin. Islet insulin secretion was significantly reduced in aging rats. L-NAME induced islet insulin secretion especially in aging rats (P=0.003). Inducible NOS activity in islets of aging rats was significantly higher than adult rats (1.082 ± 0.084 and 6.277 ± 0.475 pmol/min per mg protein in adult and aging rats, respectively, P<0.001). CONCLUSION: These findings show that decreased in islet insulin secretion may be related to increase in iNOS activity in islets, which follows impaired carbohydrate metabolism in aging.
