Nitric Oxide Overproduction Reduces Insulin Secretion from Isolated Islets in Fetal Hypothyroid Rats

Abstract

Thyroid hormones have developmental effects during fetal life. Fetal hypothyroidism leads to glucose intolerance and reduced insulin secretion capacity. Activity of nitric oxide synthases follows a heterogeneous pattern in hypothyroidism. Overactivity of constitutive nitric oxide synthase (NOS), inhibits glucose-stimulated insulin release. The aim of this study was to examine if reduction in insulin secretion in fetal hypothyroidism is due to overproduction of nitric oxide. Pregnant Wistar rats were divided into 2 groups; the experimental group consumed water containing 0.02% of 6-propyl-2-thiouracil till delivery, while the control group consumed tap water. After delivery serum thyroid hormones were measured. Intravenous glucose tolerance test was performed in 6-month old offspring (n=8). After 3 weeks recovery, pancreatic islets were isolated and insulin secretion, inducible and constitutive nitric oxide synthase activity were measured (n=4). Compared to controls, during intravenous glucose tolerance test, fetal hypothyroid rats had high plasma glucose concentration (p=0.003) and low plasma insulin levels (p=0.012) at 5–20 min and their insulin secretion from isolated islets at basal glucose concentration and in the presence of l-arginine was lower. The nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester significantly improved insulin secretion in fetal hypothyroid rats at basal glucose concentration and in the presence of l-arginine. The results showed higher NOS activities in fetal hypothyroid rats (constitutive 17.60±1.09 vs. 47.34±4.44 and inducible 4.09±0.96 vs. 19.97±1.14 pmol/min/mg proteins, p=0.002). In conclusion, NO overproduction through NOS participates in decreased insulin secretion in fetal hypothyroid rats.

Key words

NOS activity - pancreas - thyroid hormone

• References

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