A hypercaloric diet combined with a sedentary lifestyle is a major risk factor for the development of insulin resistance, type 2 diabetes mellitus (T2DM) and associated comorbidities. Standard treatment for T2DM begins with lifestyle modification, and includes oral medications and insulin therapy to compensate for progressive β-cell failure. However, current pharmaceutical options for T2DM are limited in that they do not maintain stable, durable glucose control without the need for treatment intensification. Furthermore, each medication is associated with adverse effects, which range from hypoglycaemia to weight gain or bone loss. Unexpectedly, fibroblast growth factor 1 (FGF1) and its low mitogenic variants have emerged as potentially safe candidates for restoring euglycaemia, without causing overt adverse effects. In particular, a single peripheral injection of FGF1 can lower glucose to normal levels within hours, without the risk of hypoglycaemia. Similarly, a single intracerebroventricular injection of FGF1 can induce long-lasting remission of the diabetic phenotype. This Review discusses potential mechanisms by which centrally administered FGF1 improves central glucose-sensing and peripheral glucose uptake in a sustained manner. Specifically, we explore the potential crosstalk between FGF1 and glucose-sensing neuronal circuits, hypothalamic neural stem cells and synaptic plasticity. Finally, we highlight therapeutic considerations of FGF1 and compare its metabolic actions with FGF15 (rodents), FGF19 (humans) and FGF21.

中文翻译：

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FGF1-控制2型糖尿病的新武器

高热量饮食和久坐不动的生活方式是发展胰岛素抵抗，2型糖尿病（T2DM）和相关合并症的主要危险因素。T2DM的标准治疗始于改变生活方式，包括口服药物和胰岛素治疗以补偿进行性β细胞衰竭。但是，当前用于T2DM的药物选择受到局限，因为它们不需要治疗强化就无法保持稳定，持久的葡萄糖控制。此外，每种药物都与不良反应相关，其范围从低血糖症到体重增加或骨质流失。出乎意料的是，成纤维细胞生长因子1（FGF1）及其低促有丝分裂变异体已成为恢复正常血糖的潜在安全候选者，而不会引起明显的不良影响。尤其是，单次外周注射FGF1可以在数小时内将葡萄糖降低至正常水平，而没有低血糖的风险。类似地，单次脑室内注射FGF1可以诱导糖尿病表型的持久缓解。这篇综述讨论了集中给予FGF1持续改善中心葡萄糖感应和外周葡萄糖摄取的潜在机制。具体来说，我们探讨了FGF1与葡萄糖敏感神经元回路，下丘脑神经干细胞和突触可塑性之间的潜在串扰。最后，我们重点介绍FGF1的治疗因素，并将其与FGF15（啮齿动物），FGF19（人类）和FGF21的代谢作用进行比较。脑室内单次注射FGF1可以诱导糖尿病表型的持久缓解。这篇综述讨论了集中给予FGF1持续改善中心葡萄糖感应和外周葡萄糖摄取的潜在机制。具体来说，我们探讨了FGF1与葡萄糖敏感神经元回路，下丘脑神经干细胞和突触可塑性之间的潜在串扰。最后，我们重点介绍FGF1的治疗因素，并将其与FGF15（啮齿动物），FGF19（人类）和FGF21的代谢作用进行比较。脑室内单次注射FGF1可以诱导糖尿病表型的持久缓解。这篇综述讨论了集中给予FGF1持续改善中心葡萄糖感应和外周葡萄糖摄取的潜在机制。具体来说，我们探讨了FGF1与葡萄糖敏感神经元回路，下丘脑神经干细胞和突触可塑性之间的潜在串扰。最后，我们重点介绍FGF1的治疗因素，并将其与FGF15（啮齿动物），FGF19（人类）和FGF21的代谢作用进行比较。我们探讨了FGF1与葡萄糖敏感神经元回路，下丘脑神经干细胞和突触可塑性之间的潜在串扰。最后，我们重点介绍FGF1的治疗因素，并将其与FGF15（啮齿动物），FGF19（人类）和FGF21的代谢作用进行比较。我们探讨了FGF1与葡萄糖敏感神经元回路，下丘脑神经干细胞和突触可塑性之间的潜在串扰。最后，我们重点介绍FGF1的治疗因素，并将其与FGF15（啮齿动物），FGF19（人类）和FGF21的代谢作用进行比较。