Shpilsky Gabriella F, Takahashi Hiroyuki, Aristarkhova Anna, Weil Michele, Ng Nathan, Nelson Kacie J, Lee Amanda, Zheng Hui, Kühtreiber Willem M, Faustman Denise L
Massachusetts General Hospital, Immunobiology Laboratories, Boston, MA 02129, USA.
Massachusetts General Hospital, Diabetes Unit, Boston, MA 02129, USA.
iScience. 2021 Sep 21;24(10):103150. doi: 10.1016/j.isci.2021.103150. eCollection 2021 Oct 22.
Bacillus Calmette-Guerin (BCG) vaccinations improve glycemic control in juvenile-onset Type I diabetes (T1D), an effect driven by restored sugar transport through aerobic glycolysis. In a pilot clinical trial, T1D, but not latent autoimmune diabetes of adults (LADA), exhibited lower blood sugars after multidose BCG. Using a glucose transport assay, monocytes from T1D subjects showed a large stimulation index with BCG exposures; LADA subjects showed minimal BCG-induced sugar responsiveness. Monocytes from T1D, type 2 diabetes (T2D), and non-diabetic controls (NDC) were all responsive in vitro to BCG by augmented sugar utilization. Adults with prior neonatal BCG vaccination show accelerated glucose transport decades later. Finally, in vivo experiments with the NOD mouse (a T1D model) and obese db/db mice (a T2D model) confirm BCG's blood-sugar-lowering and accelerated glucose metabolism with sufficient dosing. Our results suggest that BCG's benefits for glucose metabolism may be broadly applicable to T1D and T2D, but less to LADA.
卡介苗（BCG）接种可改善青少年发病的I型糖尿病（T1D）的血糖控制，这一效果是由通过有氧糖酵解恢复糖转运所驱动的。在一项试点临床试验中，T1D患者在多次接种BCG后血糖降低，但成年隐匿性自身免疫性糖尿病（LADA）患者并非如此。通过葡萄糖转运试验，T1D患者的单核细胞在接触BCG后显示出较大的刺激指数；LADA患者显示出最小的BCG诱导的糖反应性。来自T1D、2型糖尿病（T2D）和非糖尿病对照（NDC）的单核细胞在体外均通过增加糖利用对BCG有反应。先前接种过新生儿BCG疫苗的成年人在几十年后显示出加速的葡萄糖转运。最后，在非肥胖糖尿病（NOD）小鼠（一种T1D模型）和肥胖db/db小鼠（一种T2D模型）上进行的体内实验证实，给予足够剂量的BCG可降低血糖并加速葡萄糖代谢。我们的结果表明，BCG对葡萄糖代谢的益处可能广泛适用于T1D和T2D，但对LADA的适用性较小。
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