Nitric Oxide Overproduction Reduces Insulin Secretion from Isolated Islets in Fetal Hypothyroid Rats. 2016

Z Rouintan, and K Farrokhfall, and N Karbalaei, and A Ghasemi
Department of Physiology, Faculty of Medicine; Shahid Beheshti University of Medical Sciences, International Branch, Tehran, Iran.

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.

UI MeSH Term Description Entries
D007037 Hypothyroidism A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction. Central Hypothyroidism,Primary Hypothyroidism,Secondary Hypothyroidism,TSH Deficiency,Thyroid-Stimulating Hormone Deficiency,Central Hypothyroidisms,Deficiency, TSH,Deficiency, Thyroid-Stimulating Hormone,Hormone Deficiency, Thyroid-Stimulating,Hypothyroidism, Central,Hypothyroidism, Primary,Hypothyroidism, Secondary,Hypothyroidisms,Primary Hypothyroidisms,Secondary Hypothyroidisms,TSH Deficiencies,Thyroid Stimulating Hormone Deficiency,Thyroid-Stimulating Hormone Deficiencies
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D005260 Female Females
D005315 Fetal Diseases Pathophysiological conditions of the FETUS in the UTERUS. Some fetal diseases may be treated with FETAL THERAPIES. Embryopathies,Disease, Fetal,Diseases, Fetal,Embryopathy,Fetal Disease
D000078790 Insulin Secretion Production and release of insulin from PANCREATIC BETA CELLS that primarily occurs in response to elevated BLOOD GLUCOSE levels. Secretion, Insulin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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