Jevtovic Filip
Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC, USA.
Diabetes Metab Syndr Obes. 2021 Sep 16;14:4043-4057. doi: 10.2147/DMSO.S328694. eCollection 2021.
Excess nutrient intake and lack of exercise characterize the problem of obesity and are common factors in insulin resistance (IR). With an increasing number of prediabetic, and type 2 diabetic populations, metformin is still the most prescribed glucose-lowering drug and is often accompanied by recommendations for regular physical exercise. Metformin, by the inhibition of complex 1 of the electron transport chain, and exercise, by increasing energy expenditure, both elicit a low cellular energy state that leads to improvements in glucose control via activation of adenosine 5' monophosphate-activated protein kinase (AMPK). An augmented stimulation of the energy-sensing enzyme AMPK by either of the two modalities leads to an increase in glycogenolysis, glucose uptake, fat oxidation, a decrease in glycogen and protein synthesis, and gluconeogenesis in muscle and the liver, which are remarked as having positive effects on metabolic pathophysiology observed in IR and type 2 diabetes mellitus (T2DM). While both modalities exploit the energy-sensing enzyme AMPK to attain glucose homeostasis, the synergistic effect of these two treatments is not distinctly supported by the literature. Further, an antagonistic dynamic has been observed in cases where metformin and exercise were combined. Reduction of insulin-sensitizing effects of exercise and an overall hindrance of exercise performance and adaptations have been reported and could suggest the possible incongruity of these two modalities. The aim of this review is to elucidate the effect that metformin and exercise have on the management of the metabolic abnormalities observed in T2DM and to provide an insight into the interaction of these two modalities.
营养摄入过多和缺乏运动是肥胖问题的特征，也是胰岛素抵抗（IR）的常见因素。随着糖尿病前期和2型糖尿病患者数量的增加，二甲双胍仍然是最常用的降糖药物，并且经常伴随着定期体育锻炼的建议。二甲双胍通过抑制电子传递链的复合物1，而运动通过增加能量消耗，两者都引发低细胞能量状态，进而通过激活5'-单磷酸腺苷激活蛋白激酶（AMPK）来改善血糖控制。这两种方式中任何一种对能量感应酶AMPK的增强刺激都会导致糖原分解增加、葡萄糖摄取增加、脂肪氧化增加、肌肉和肝脏中糖原和蛋白质合成减少以及糖异生减少，这些被认为对IR和2型糖尿病（T2DM）中观察到的代谢病理生理学具有积极影响。虽然这两种方式都利用能量感应酶AMPK来实现葡萄糖稳态，但这两种治疗方法的协同作用并未得到文献的明确支持。此外，在二甲双胍与运动联合使用的情况下观察到了拮抗作用。有报道称运动的胰岛素增敏作用降低以及运动表现和适应性的整体阻碍，这可能表明这两种方式可能不协调。本综述的目的是阐明二甲双胍和运动对T2DM中观察到的代谢异常管理的影响，并深入了解这两种方式的相互作用。
