Statin Treatment-Induced Development of Type 2 Diabetes: From Clinical Evidence to Mechanistic Insights
Abstract
:1. Introduction
2. Primary Action of Statins: Cholesterol Biosynthetic Pathway
3. Beneficial Effects of Statins on Diabetic Complication and/or Inflammation in T2DM
4. Statin Therapy and Risk of Developing T2DM: Observational Studies, Clinical Trials and Meta-Analysis
5. Proposed Mechanisms for T2DM Development Induced by Statins
5.1. Dysfunctional Effects Caused by Statins in Pancreatic β-Cell
5.2. Statin Induced IR
5.2.1. Adipose Tissue
5.2.2. Skeletal Muscle
5.2.3. Liver
5.3. MicroRNAs and Impact of Statin Therapy on microRNA Expression Profile
5.3.1. miR Modulation of Cholesterol and Lipid Homeostasis
5.3.2. Modulation of Hepatic Glucose Production
5.3.3. Modulation of the Insulin Signaling Pathway
6. Differences in Diabetogenic Effects between Hydrophilic and Lipophilic Statins
7. Conclusions
Funding
Conflicts of Interest
Abbreviations
Cav-1 | Caveolin 1 |
CVD | Cardiovascular disease |
FASN | Fatty-acid synthase |
FFA | Free fatty acids |
G-proteins | Small GTP-binding proteins |
G6Pase | Glucose-6-phosphatase |
GLUT-4 | Insulin-responsive glucose transporter 4 |
GSIS | Stimulated insulin secretion |
HMG-CoA | 3-hydroxy-3-methyl-glutaryl coenzyme-A |
INSR | Insulin receptor |
IRS | Insulin receptor substrates |
LDL-C | LDL cholesterol |
LDLR | LDL receptor |
miR | MicroRNA |
PEPCK | Phosphoenolpyruvate carboxykinase |
PP2A | Protein phosphatase 2a |
PP2CA | Protein phosphatase 2CA |
PTPAses | Protein tyrosine phosphatases |
PXR | Pregnane X receptor |
RCT | Randomized control trials |
SGK2 | Serum/glucocorticoid regulated kinase 2 |
T2DM | Type 2 diabetes mellitus |
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Galicia-Garcia, U.; Jebari, S.; Larrea-Sebal, A.; Uribe, K.B.; Siddiqi, H.; Ostolaza, H.; Benito-Vicente, A.; Martín, C. Statin Treatment-Induced Development of Type 2 Diabetes: From Clinical Evidence to Mechanistic Insights. Int. J. Mol. Sci. 2020, 21, 4725. https://doi.org/10.3390/ijms21134725
Galicia-Garcia U, Jebari S, Larrea-Sebal A, Uribe KB, Siddiqi H, Ostolaza H, Benito-Vicente A, Martín C. Statin Treatment-Induced Development of Type 2 Diabetes: From Clinical Evidence to Mechanistic Insights. International Journal of Molecular Sciences. 2020; 21(13):4725. https://doi.org/10.3390/ijms21134725
Chicago/Turabian StyleGalicia-Garcia, Unai, Shifa Jebari, Asier Larrea-Sebal, Kepa B. Uribe, Haziq Siddiqi, Helena Ostolaza, Asier Benito-Vicente, and César Martín. 2020. "Statin Treatment-Induced Development of Type 2 Diabetes: From Clinical Evidence to Mechanistic Insights" International Journal of Molecular Sciences 21, no. 13: 4725. https://doi.org/10.3390/ijms21134725