Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Nat Commun. 2021 Dec 6;12(1):7080. doi: 10.1038/s41467-021-27187-7.
Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.
男性通常比女性更容易出现葡萄糖代谢受损和 2 型糖尿病（T2D）。然而，其潜在机制仍有待确定。在这里，我们揭示了肠道微生物组耗竭消除了葡萄糖代谢的性别二态性。将雄性供体微生物群转移到接受抗生素治疗的雌性小鼠中，导致受体的胰岛素抵抗更严重。通过阉割去除雄激素会使雄性小鼠的肠道微生物组变得更类似于雌性，并改善葡萄糖代谢，而重新引入二氢睾酮（DHT）则会逆转这些变化。更重要的是，当肠道微生物组被耗竭时，雄激素对葡萄糖代谢的影响在很大程度上被消除。接下来，我们证明雄激素通过调节循环谷氨酰胺和谷氨酰胺/谷氨酸（Gln/Glu）比值来部分调节葡萄糖代谢，而补充谷氨酰胺可增加体外胰岛素敏感性。我们的研究表明，雄激素通过调节肠道微生物组和循环谷氨酰胺和 Gln/Glu 比值来部分影响葡萄糖稳态，从而导致两性之间葡萄糖代谢的差异。
