Ibrahim Manal, Ahmeid Mutaz
Master of Clinical Biochemistry, College of Pharmacy /University of Mosul, Iraq.
Ph.D. Clinical Biochemistry, College of Medicine /University of Tikrit, Iraq.
ADMET DMPK. 2022 Dec 9;9(1):49-55. doi: 10.5599/admet.905. eCollection 2021.
Zonulin protein is a haptoglobin precursor and functions to modulate the permeability of tight junctions between enterocytes. Local inflammation or systemic inflammation can trigger zonulin expression. While the increased zonulin level causes an increase of intestinal permeability and entrance of foreign antigens, the latter can increase insulin resistance and inflammation. Polycystic ovarian syndrome affects women during their reproductive age characterized by hyperinsulinemia and/or hyperandrogenemia and associated with infertility problems. Changes in gut permeability such as irritable bowel syndrome are often found in PCOS patients. While metformin increases insulin mediates glucose uptake and, acts as an insulin-sensitizing drug used to treat PCOS patients is recently discovered to reshape intestinal bacteria and hence may affect intestinal action. This study was designed to find any association between zonulin level and other parameters in PCOS patients and to find metformin treatment effects on zonulin in PCOS patients. Thirty-one newly diagnosed PCOS women agree to take metformin 850 mg twice daily for three months and, and to give fasting serum samples to measure zonulin, FSH, LH, total testosterone, free testosterone, SHBG, fasting insulin, and fasting serum glucose before and after treatment. The free testosterone and zonulin are determined by the ELISA technique while the other parameters are determined by the Cobas technique. According to patients' Homeostatic Model Assessment (HOMA-IR), the Patients were divided into two sub-groups: the first group consisting of those with initial HOMA-IR less than two and the second group was those of an initial HOMA-IR of between two to four. Whereas the first group showed no significant response to treatment, the second group showed a better response to metformin treatment, as demonstrated by their LH, total testosterone, free testosterone, fasting insulin, zonulin, and glucose levels. These parameters markedly improved after metformin treatment with p-values of 0.08, 0.09, 0.07. 0.04, 0.01 and 0.06, respectively.
闭合蛋白是一种触珠蛋白前体,其功能是调节肠上皮细胞间紧密连接的通透性。局部炎症或全身炎症均可触发闭合蛋白的表达。闭合蛋白水平升高会导致肠道通透性增加以及外来抗原进入,而后者会增加胰岛素抵抗和炎症反应。多囊卵巢综合征影响育龄期女性,其特征为高胰岛素血症和/或高雄激素血症,并伴有不孕问题。多囊卵巢综合征患者常出现肠道通透性改变,如肠易激综合征。二甲双胍可增加胰岛素介导的葡萄糖摄取,作为一种用于治疗多囊卵巢综合征患者的胰岛素增敏药物,最近发现它可重塑肠道菌群,因此可能影响肠道功能。本研究旨在探寻多囊卵巢综合征患者闭合蛋白水平与其他参数之间的关联,以及二甲双胍治疗对多囊卵巢综合征患者闭合蛋白的影响。31名新诊断的多囊卵巢综合征女性同意每日两次服用850毫克二甲双胍,为期三个月,并在治疗前后提供空腹血清样本,以检测闭合蛋白、促卵泡生成素、促黄体生成素、总睾酮、游离睾酮、性激素结合球蛋白、空腹胰岛素和空腹血糖。游离睾酮和闭合蛋白通过酶联免疫吸附测定技术测定,而其他参数通过 Cobas 技术测定。根据患者的稳态模型评估(HOMA-IR),将患者分为两个亚组:第一组初始HOMA-IR小于2,第二组初始HOMA-IR在2至4之间。第一组对治疗无明显反应,而第二组对二甲双胍治疗反应较好,其促黄体生成素、总睾酮、游离睾酮、空腹胰岛素、闭合蛋白和血糖水平均有所改善。二甲双胍治疗后,这些参数显著改善,p值分别为0.08、0.09、0.07、0.04、0.01和0.06。