Department of Stem Cell and Regenerative Medicine, State Key laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Military Medical University, Chongqing, P.R. China.
Central Laboratory, State Key laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Military Medical University, Chongqing, P.R. China.
Sci Rep. 2019 Nov 28;9(1):17764. doi: 10.1038/s41598-019-54291-y.
Micro- and macro-vascular events are directly associated with hyperglycemia in patients with type 2 diabetes mellitus (TDM), but whether intensive glucose control decreases the risk of diabetic cardiovascular complications remains uncertain. Many studies have confirmed that impaired quality and quantity of mesenchymal stem cells (MSCs) plays a pathogenic role in diabetes. Our previous study found that the abundance of circulating MSCs was significantly decreased in patients with TDM, which was correlated with the progression of diabetic complications. In addition, metformin-induced MSC apoptosis is one of the reasons for the decreased quantity of endogenous or exogenous MSCs during intensive glucose control. However, the role of glucose in metformin-induced MSC apoptosis during intensive glucose control in TDM remains unknown. In this study, we found that metformin induces MSC apoptosis during intensive glucose control, while high glucose (standard glucose control) could significantly reverse its adverse effect in an AMPK-mTOR pathway dependent manner. Thus, our results indicate that the poorer clinical benefit of the intensive glucose control strategy may be related to an adverse effect due to metformin-induced MSC apoptosis during intensive glucose control therapy in patients with TDM.
微血管和大血管事件与 2 型糖尿病（T2DM）患者的高血糖直接相关，但强化血糖控制是否降低糖尿病心血管并发症的风险仍不确定。许多研究证实，间充质干细胞（MSCs）的质量和数量受损在糖尿病发病机制中起致病作用。我们之前的研究发现，T2DM 患者循环 MSC 的丰度显著降低，这与糖尿病并发症的进展相关。此外，二甲双胍诱导的 MSC 凋亡是强化血糖控制期间内源性或外源性 MSC 数量减少的原因之一。然而，在 T2DM 强化血糖控制期间，葡萄糖在二甲双胍诱导的 MSC 凋亡中的作用尚不清楚。在这项研究中，我们发现二甲双胍在强化血糖控制过程中诱导 MSC 凋亡，而高葡萄糖（标准血糖控制）可通过 AMPK-mTOR 通路依赖性方式显著逆转其不良作用。因此，我们的结果表明，强化血糖控制策略较差的临床获益可能与 T2DM 患者强化血糖控制治疗期间二甲双胍诱导的 MSC 凋亡的不良作用有关。
