Padder Khurshid Ahmad, Yousuf Mohmad Aadil, Jahan Nusrat, Yousuf Syed Douhath, Ganie Mohd Ashraf
Department of Endocrinology, Sher-i- Kashmir Institute of Medical Sciences, Srinagar, India.
Department of Life Sciences, Jaipur National University, Jaipur, India.
Endocrine. 2025 Apr;88(1):323-329. doi: 10.1007/s12020-024-04137-z. Epub 2024 Dec 27.
Polycystic ovary syndrome (PCOS) represents a multifaceted endocrine, reproductive, and metabolic disorder characterized by hyperandrogenism and hyperinsulinemia-induced insulin resistance (IR). Recent studies reported that the etiology of PCOS is likely correlated with genes involved in steriodogenesis, IR and glucose metabolism. Among the candidate genes in insulin signaling pathways, RAB5B, a small GTPase involved in vesicle trafficking, significantly impacts cellular pathways in ovarian follicular cells, leading to clinical and endocrine changes among women with PCOS. Additionally, RAB5B is crucial for insulin-mediated glucose uptake and is involved in PI3K, AKT, and MAPK/ERK pathways, affecting LHCGR-stimulated steroidogenesis. Despite extensive research, the precise molecular mechanisms underlying RAB5B mediated IR in PCOS remained elusive.
The study aimed to explore the potential link between RAB5B gene expression and IR among women with PCOS.
A total of age matched 270 subjects were enrolled in this study including 135 PCOS women and 135 apparently healthy controls. These study participants were subjected to detailed medical history, clinical and physical examination. All subjects were further evaluated for biochemical, hormonal and RAB5B gene expression estimation. Expression levels of RAB5B gene were analyzed using gene-specific primers and the SYBR® Green PCR Kit (Qiagen, Germany) and their qPCR reaction mix, according to the manufacturer's guidelines. Student t-test and ANOVA were used to evaluate the differences in the means of various parameters.
The HOMA-IR (2.28 ± 1.4 vs. 1.36 ± 0.73) was significantly elevated among women with PCOS than controls (p < 0.05). We also found that the QUICKI (0.35 ± 0.04 vs. 0.37 ± 0.04), MATSUDA (12.59 ± 4.71 vs. 15.47 ± 4.33) and FGIR (11.56 ± 7.06 vs. 14.32 ± 8.66) were higher in controls than women with PCOS (p < 0.05). We also observed that women with PCOS had elevated levels of RAB5B mRNA levels when compared with apparently healthy controls. Bivariate correlation analysis among HOMA-IR stratified PCOS and control subjects revealed strong negative correlation between IR PCOS and IR PCOS (r = -0.61, P < 0.05) and IR control (r = -0.37, p < 0.05) subjects respectively.
Our study demonstrated that there is potential link between RAB5B gene expression and IR specifically in the context of IR indices among women with PCOS.
多囊卵巢综合征（PCOS）是一种多方面的内分泌、生殖和代谢紊乱疾病，其特征为高雄激素血症以及高胰岛素血症诱导的胰岛素抵抗（IR）。近期研究报道，PCOS的病因可能与参与类固醇生成、IR和葡萄糖代谢的基因相关。在胰岛素信号通路的候选基因中，RAB5B是一种参与囊泡运输的小GTP酶，它对卵巢卵泡细胞中的细胞通路有显著影响，导致PCOS女性出现临床和内分泌变化。此外，RAB5B对胰岛素介导的葡萄糖摄取至关重要，并参与PI3K、AKT和MAPK/ERK通路，影响促黄体生成素/绒毛膜促性腺激素受体（LHCGR）刺激的类固醇生成。尽管进行了广泛研究，但PCOS中RAB5B介导IR的精确分子机制仍不清楚。
本研究旨在探讨PCOS女性中RAB5B基因表达与IR之间的潜在联系。
本研究共纳入270名年龄匹配的受试者，包括135名PCOS女性和135名明显健康的对照者。这些研究参与者接受了详细的病史、临床和体格检查。所有受试者进一步进行生化、激素和RAB5B基因表达评估。根据制造商的指南，使用基因特异性引物和SYBR® Green PCR试剂盒（德国Qiagen公司）及其qPCR反应混合物分析RAB5B基因的表达水平。采用学生t检验和方差分析评估各项参数均值的差异。
PCOS女性的稳态模型评估胰岛素抵抗（HOMA-IR）（2.28±1.4 vs. 1.36±0.73）显著高于对照组（p<0.05）。我们还发现，对照组的定量胰岛素敏感性检查指数（QUICKI）（0.35±0.04 vs. 0.37±0.04）、松田指数（MATSUDA）（12.59±4.71 vs. 15.47±4.33）和空腹血糖胰岛素抵抗指数（FGIR）（11.56±7.06 vs. 14.32±8.66）均高于PCOS女性（p<0.05）。我们还观察到，与明显健康的对照组相比，PCOS女性的RAB5B mRNA水平升高。对按HOMA-IR分层的PCOS和对照受试者进行双变量相关性分析发现，IR PCOS与IR PCOS受试者（r=-0.61，P<0.05）和IR对照受试者（r=-0.37，p<0.05）之间分别存在强负相关。
我们的研究表明，RAB5B基因表达与IR之间存在潜在联系，特别是在PCOS女性的IR指标方面。
