Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
Endocrinology. 2022 Oct 11;163(11). doi: 10.1210/endocr/bqac162.
Metformin improves insulin's action on whole-body glucose metabolism in various insulin-resistant populations. The detailed cellular mechanism(s) for its metabolic actions are multiple and still incompletely understood. Beyond metabolic actions, metformin also impacts microvascular function. However, the effects of metformin on microvascular function and microvascular insulin action specifically are poorly defined. In this mini-review, we summarize what is currently known about metformin's beneficial impact on both microvascular function and the microvascular response to insulin while highlighting methodologic issues in the literature that limit straightforward mechanistic understanding of these effects. We examine potential mechanisms for these effects based on pharmacologically dosed studies and propose that metformin may improve human microvascular insulin resistance by attenuating oxidative stress, inflammation, and endothelial dysfunction. Finally, we explore several important evidence gaps and discuss avenues for future investigation that may clarify whether metformin's ability to improve microvascular insulin sensitivity is linked to its positive impact on vascular outcomes.
二甲双胍可改善各种胰岛素抵抗人群全身葡萄糖代谢对胰岛素的作用。其代谢作用的详细细胞机制尚不清楚。除代谢作用外，二甲双胍还可影响微血管功能。然而，二甲双胍对微血管功能和微血管胰岛素作用的影响尚不清楚。在这篇小型综述中，我们总结了目前已知的二甲双胍对微血管功能和胰岛素对微血管作用的有益影响，同时强调了文献中方法学问题限制了对这些影响的直接机制理解。我们根据药物剂量研究检查了这些影响的潜在机制，并提出二甲双胍可能通过减轻氧化应激、炎症和内皮功能障碍来改善人类微血管胰岛素抵抗。最后，我们探讨了一些重要的证据差距，并讨论了未来研究的途径，这可能有助于阐明二甲双胍改善微血管胰岛素敏感性的能力是否与其对血管结局的积极影响有关。
