Karbalaei Narges, Ghasemi Asghar, Hedayati Mehdi, Godini Aliashraf, Zahediasl Saleh
* Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19395-4763 Tehran, Islamic Republic of Iran.
Exp Physiol. 2014 Apr;99(4):701-14. doi: 10.1113/expphysiol.2013.073825. Epub 2013 Oct 4.
Previous studies have recently shown that maternal hypothyroidism leads to impaired glucose metabolism and reduced insulin secretion in adult offspring in rats. The aim of this study was to locate the defect in the insulin secretion pathway induced by maternal hypothyroidism. Pregnant Wistar rats were divided into two groups; the control group consumed water, while the hypothyroid (FH) group received water containing 0.025% 6-propyl-2-thiouracil during gestation. An intravenous glucose tolerance test was carried out on 5-month-old male offspring. In in vitro studies, the effects of various secretagogues and inhibitors acting at different levels of the insulin secretion cascade were investigated, and insulin content, insulin secretion and glucokinase activity of the islets were compared. Although insulin content of the FH islets did not differ from that of control islets, insulin secretion from FH islets was reduced when it was challenged by glucose or arginine. Compared with control islets, activities of both hexokinase and glucokinase were also significantly decreased in the FH islets. Although, in both groups, increasing glibenclamide and nifedipine concentrations in the presence of 16.7 mmol l(-1) glucose increased and decreased insulin secretion, respectively, the percentage of changes in secretion of FH islets was significantly lower compared with control islets. The response of FH islets to high extracellular potassium concentration and diazoxide was also significantly lower than that of the control islets. These findings demonstrate that impaired insulin secretion in the FH group is probably related to alterations in different steps of the insulin secretion pathway and not in the insulin pool of β-cells.
先前的研究最近表明，母体甲状腺功能减退会导致成年大鼠后代的葡萄糖代谢受损和胰岛素分泌减少。本研究的目的是确定母体甲状腺功能减退诱导的胰岛素分泌途径中的缺陷。将怀孕的Wistar大鼠分为两组；对照组饮用自来水，而甲状腺功能减退（FH）组在妊娠期饮用含0.025% 6-丙基-2-硫氧嘧啶的水。对5月龄雄性后代进行静脉葡萄糖耐量试验。在体外研究中，研究了作用于胰岛素分泌级联不同水平的各种促分泌剂和抑制剂的作用，并比较了胰岛的胰岛素含量、胰岛素分泌和葡萄糖激酶活性。虽然FH组胰岛的胰岛素含量与对照组胰岛无差异，但当受到葡萄糖或精氨酸刺激时，FH组胰岛的胰岛素分泌减少。与对照组胰岛相比，FH组胰岛中己糖激酶和葡萄糖激酶的活性也显著降低。虽然在两组中，在16.7 mmol l(-1)葡萄糖存在下增加格列本脲和硝苯地平浓度分别增加和减少胰岛素分泌，但FH组胰岛分泌变化的百分比与对照组胰岛相比显著更低。FH组胰岛对高细胞外钾浓度和二氮嗪的反应也显著低于对照组胰岛。这些发现表明，FH组胰岛素分泌受损可能与胰岛素分泌途径不同步骤的改变有关，而不是与β细胞的胰岛素储备有关。
