Full title: High glucose protects mesenchymal stem cells from metformin-induced apoptosis through the AMPK-mediated mTOR pathway

Micro- and macro-vascular events are directly associated with hyperglycemia in patients with type 2 diabetes mellitus (T DM), but whether intensive glucose control decreases the risk of diabetic cardiovascular complications remains uncertain. Many studies have confirmed that impaired quality and qua...

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Bibliographic Details
Published in:Scientific reports 2019-11, Vol.9 (1), p.17764-9, Article 17764
Main Authors: He, Xiao, Yang, Yi, Yao, Meng-Wei, Ren, Ting-Ting, Guo, Wei, Li, Ling, Xu, Xiang
Format: Article
Language:English
Subjects:
AMP-Activated Protein Kinases - metabolism
Animals
Antidiabetics
Apoptosis
Apoptosis - drug effects
Cardiovascular diseases
Cell Line
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
Glucose
Glucose - metabolism
Humans
Hyperglycemia
Hyperglycemia - drug therapy
Hyperglycemia - metabolism
Hypoglycemic Agents - adverse effects
Hypoglycemic Agents - therapeutic use
Male
Mesenchymal stem cells
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - drug effects
Mesenchymal Stem Cells - metabolism
Mesenchyme
Metformin
Metformin - adverse effects
Metformin - therapeutic use
Mice
Side effects
Signal Transduction - drug effects
Stem cells
TOR protein
TOR Serine-Threonine Kinases - metabolism
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Summary:Micro- and macro-vascular events are directly associated with hyperglycemia in patients with type 2 diabetes mellitus (T DM), 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 T DM, 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 T DM 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 T DM.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-54291-y