Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, 226031, India; AcSIR, CSIR-Central Drug Research Institute Campus, Lucknow, 226031, India.
Zydus Research Center, Moraiya, Ahmedabad, 382213, Gujarat, India.
Mol Cell Endocrinol. 2022 Jan 15;540:111525. doi: 10.1016/j.mce.2021.111525. Epub 2021 Nov 29.
Adiponectin and insulin resistance creates a vicious cycle that exacerbates type 2 diabetes. Earlier, we observed that female leptin receptor-deficient BLKS mice (BKS-db/db) were more sensitive to an adiponectin mimetic GTDF than males, which led us to explore if E2 plays a crucial role in modulation of adiponectin-sensitivity. Male but not female BKS-db/db mice were resistant to metabolic effects of globular adiponectin treatment. Male BKS-db/db displayed reduced skeletal muscle AdipoR1 protein expression, which was consequent to elevated polypyrimidine tract binding protein 1 (PTB) and miR-221. E2 treatment in male BKS-db/db, and ovariectomized BALB/c mice rescued AdipoR1 protein expression via downregulation of PTB and miR-221, and also directly increased AdipoR1 mRNA by its classical nuclear receptors. Estrogen receptor regulation via dietary or pharmacological interventions may improve adiponectin resistance and consequently ameliorate insulin resistance in type 2 diabetes.
脂联素和胰岛素抵抗形成恶性循环，使 2 型糖尿病恶化。我们之前观察到，雌性瘦素受体缺陷 BLKS 小鼠（BKS-db/db）对脂联素类似物 GTDF 的敏感性高于雄性，这促使我们探讨 E2 是否在调节脂联素敏感性方面发挥关键作用。雄性而非雌性 BKS-db/db 小鼠对球状脂联素治疗的代谢作用有抗性。雄性 BKS-db/db 小鼠的骨骼肌 AdipoR1 蛋白表达减少，这是由于多嘧啶 tract 结合蛋白 1（PTB）和 miR-221 升高所致。E2 处理雄性 BKS-db/db 和去卵巢 BALB/c 小鼠，通过下调 PTB 和 miR-221 来挽救 AdipoR1 蛋白表达，也通过其经典核受体直接增加 AdipoR1 mRNA。通过饮食或药物干预雌激素受体调节可能改善脂联素抵抗，从而改善 2 型糖尿病的胰岛素抵抗。
