Amsterdam University Medical Centers, location Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Crit Care. 2024 Feb 29;28(1):65. doi: 10.1186/s13054-024-04829-y.
SARS-CoV-2 can induce insulin resistance, which is, among others, mediated by adipose tissue dysfunction and reduced angiotensin-converting enzyme 2 (ACE2) enzymatic activity. In SARS-CoV-2-infected mice, the tyrosine kinase inhibitor imatinib attenuates inflammation and improves insulin sensitivity. Here, we report the effects of imatinib on incident hyperglycaemia, circulating levels of glucoregulatory proteins, longitudinal insulin sensitivity and ACE-2 enzymatic activity in 385 hospitalized COVID-19 patients who participated in a randomized, double-blind, placebo-controlled clinical trial. Patients with severe hyperglycaemia had similar demographics compared to those without, but required longer hospital stays and exhibited higher invasive ventilation and mortality rates. The incidence of severe hyperglycaemia was significantly lower in patients treated with imatinib, while insulin production and central insulin sensitivity were unaffected. Imatinib increased plasma angiotensin-2 and adiponectin levels, and decreased c-Jun N-terminal protein kinase 1 (JNK1), JNK2 and interleukin-6 levels. These findings suggest that imatinib restores endocrine control of peripheral glucose uptake in COVID-19.
SARS-CoV-2 可诱导胰岛素抵抗，这是由脂肪组织功能障碍和血管紧张素转化酶 2（ACE2）酶活性降低介导的。在感染 SARS-CoV-2 的小鼠中，酪氨酸激酶抑制剂伊马替尼可减轻炎症并改善胰岛素敏感性。在这里，我们报告了伊马替尼对 385 名参与随机、双盲、安慰剂对照临床试验的 COVID-19 住院患者的新发高血糖、糖调节蛋白循环水平、纵向胰岛素敏感性和 ACE-2 酶活性的影响。与无严重高血糖的患者相比，严重高血糖患者的人口统计学特征相似，但需要更长的住院时间，并且表现出更高的有创通气和死亡率。与安慰剂相比，接受伊马替尼治疗的患者严重高血糖的发生率显著降低，而胰岛素分泌和中枢胰岛素敏感性不受影响。伊马替尼增加了血浆血管紧张素-2 和脂联素水平，降低了 c-Jun N-末端蛋白激酶 1（JNK1）、JNK2 和白细胞介素-6 水平。这些发现表明，伊马替尼恢复了 COVID-19 外周葡萄糖摄取的内分泌控制。
