Comparison of the effect of maternal hypothyroidism on carbohydrate metabolism in young and aged male offspring in rats

Abstract

Objective. Since thyroid hormones play fundamental roles in somatic growth and metabolism, disturbances of thyroid function affect many organs and systems. Both fetal hypothyroidism and aging can affect carbohydrate metabolism during adult life. This study aims to assess the glucose tolerance and insulin secretion capacity of islets in young and aged male offspring of mothers who were hypothyroid during pregnancy. Materials and methods. Pregnant Wistar rats were divided into two groups; the control group consumed water, while the hypothyroid group received water containing 0.02% of 6-propyl-2-thiouracil (200 ppm) during gestation. After birth, survival and weight of pups from both groups were followed. The intravenous glucose tolerance test (IVGTT, 0.5 g/kg glucose) was carried out in young and aged male offspring (at 3- and 12-months-old). Results. In old, but not in young rats, serum glucose and insulin levels were respectively significantly higher and lower between 5 and 20 min in the fetal hypothyroid (FH) group, compared with the controls (C). Insulin secretion of the isolated islets stimulated with 5.6, 8.3, and 16 mmol/L glucose in the old FH group (240.5 ± 22.0, 457.0 ± 40.1, and 768.0 ± 57.1 respectively) were significantly lower (p = 0.014, p = 0.029 and p = 0.003 respectively), compared to the C group (327.9 ± 25.9, 579.2 ± 36.3, and 1024.0 ± 59.5 pmol/islet/min respectively). Conclusion. Results show that maternal hypothyroidism leads to glucose intolerance and reduced insulin secretion capacity, more obvious in older offspring. Hence it can be concluded that the effect of fetal hypothyroidism on carbohydrate metabolism may contribute to increased risk of type II diabetes in aged animals.

Key Words::

• Hypothyroidism
• carbohydrate metabolism
• insulin
• glucose tolerance test
• aging
• rats

Acknowledgements

The authors wish to thank Ms N. Shiva for linguistic editing.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported in part by a grant (No. 363) funding from the Research Institute for Endocrine Sciences of Shahid Beheshti University of Medical Sciences, and is a part of Ph.D thesis for Narges Karbalaei.