Abstract |
Metformin exhibits diverse protective effects against diabetic complications, such as bone loss. Here, we investigated the effect of metformin on vascular calcification, another type 2 diabetes complication. In female rat aortic smooth muscle cells (RASMCs), we observed that metformin significantly alleviated β- glycerophosphate-induced Ca deposition and alkaline phosphatase activity, corresponding with reduced expression of some specific genes in osteoblast-like cells, including Runx2 and bone morphogenetic protein-2, and positive effects on α-actin expression, a specific marker of smooth muscle cells. Mechanistic analysis showed that phosphorylation levels of both AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) were increased with NO overproduction. After inhibition of either AMPK or eNOS with the pharmacologic inhibitors, compound C or Nω-Nitro- L-arginine methyl ester, NO production was lowered and metformin-meditated vascular protection against β- glycerophosphate-induced Ca deposition was removed. Our results support that metformin prevents vascular calcification via AMPK-eNOS-NO pathway.
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Authors | Xiaorui Cao, Huan Li, Huiren Tao, Ning Wu, Lifeng Yu, Dawei Zhang, Xiaozhao Lu, Jinyu Zhu, Zifan Lu, Qingsheng Zhu |
Journal | Endocrinology
(Endocrinology)
Vol. 154
Issue 10
Pg. 3680-9
(Oct 2013)
ISSN: 1945-7170 [Electronic] United States |
PMID | 24025223
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Glycerophosphates
- Hypoglycemic Agents
- Protein Kinase Inhibitors
- Nitric Oxide
- Metformin
- Nitric Oxide Synthase Type III
- Nos3 protein, mouse
- AMP-Activated Protein Kinases
- beta-glycerophosphoric acid
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Topics |
- AMP-Activated Protein Kinases
(antagonists & inhibitors, chemistry, metabolism)
- Animals
- Aorta
(cytology, drug effects, metabolism, pathology)
- Cell Transdifferentiation
(drug effects)
- Cells, Cultured
- Diabetic Angiopathies
(chemically induced, metabolism, pathology, prevention & control)
- Enzyme Activation
(drug effects)
- Enzyme Inhibitors
(adverse effects)
- Female
- Glycerophosphates
(adverse effects, antagonists & inhibitors)
- Hypoglycemic Agents
(antagonists & inhibitors, pharmacology)
- Metformin
(antagonists & inhibitors, pharmacology)
- Muscle, Smooth, Vascular
(cytology, drug effects, metabolism, pathology)
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase Type III
(antagonists & inhibitors, chemistry, metabolism)
- Phosphorylation
(drug effects)
- Protein Kinase Inhibitors
(adverse effects)
- Protein Processing, Post-Translational
(drug effects)
- Rats
- Rats, Sprague-Dawley
- Signal Transduction
(drug effects)
- Vascular Calcification
(chemically induced, metabolism, pathology, prevention & control)
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