Abstract
Sedentary life style and high calorie dietary habits are prominent leading cause of metabolic syndrome in modern world. Obesity plays a central role in occurrence of various diseases like hyperinsulinemia, hyperglycemia and hyperlipidemia, which lead to insulin resistance and metabolic derangements like cardiovascular diseases (CVDs) mediated by oxidative stress. The mortality rate due to CVDs is on the rise in developing countries. Insulin resistance (IR) leads to micro or macro angiopathy, peripheral arterial dysfunction, hampered blood flow, hypertension, as well as the cardiomyocyte and the endothelial cell dysfunctions, thus increasing risk factors for coronary artery blockage, stroke and heart failure suggesting that there is a strong association between IR and CVDs. The plausible linkages between these two pathophysiological conditions are altered levels of insulin signaling proteins such as IR-β, IRS-1, PI3K, Akt, Glut4 and PGC-1α that hamper insulin-mediated glucose uptake as well as other functions of insulin in the cardiomyocytes and the endothelial cells of the heart. Reduced AMPK, PFK-2 and elevated levels of NADP(H)-dependent oxidases produced by activated M1 macrophages of the adipose tissue and elevated levels of circulating angiotensin are also cause of CVD in diabetes mellitus condition. Insulin sensitizers, angiotensin blockers, superoxide scavengers are used as therapeutics in the amelioration of CVD. It evidently becomes important to unravel the mechanisms of the association between IR and CVDs in order to formulate novel efficient drugs to treat patients suffering from insulin resistance-mediated cardiovascular diseases. The possible associations between insulin resistance and cardiovascular diseases are reviewed here.
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Abbreviations
- ACE:
-
Angiotensin-converting enzyme
- ARBs:
-
Angiotensin receptor blockers
- ADA:
-
American Diabetes Association
- AGEs:
-
Advanced glycation end-products
- AMPK:
-
AMP-activated protein kinase
- AT1R:
-
Angiotensin II type I receptor
- C/EBP:
-
CCAAT/enhancer binding protein
- CAN:
-
Cardiac autonomic neuropathy
- CRP:
-
C-reactive protein
- CVD:
-
Cardio vascular diseases
- DG:
-
Diacyl glycerol
- DM:
-
Diabetes mellitus
- eNOS:
-
Endothelial nitric oxide synthase
- ERR:
-
Estrogen-related nuclear receptors
- ET-1:
-
Endothelin-1
- FAT/CD36:
-
Fatty acid translocase
- FetA:
-
Fetuin-A
- FFA:
-
Free fatty acid
- Glut4:
-
Glucose transporter 4
- HDL:
-
High-density lipoprotein
- HO-1:
-
Heme oxygenase-1
- ICAM-1:
-
Intracellular adhesion molecule-1
- IL-6:
-
Interleukin-6
- IR:
-
Insulin resistance
- IR-β:
-
Insulin receptor β
- IRS-1:
-
Insulin receptor substrate-1
- JNK:
-
Janus kinase
- STAT:
-
Signal transducer and activator of transcription
- LCFA:
-
Long-chain fatty acid
- LDL:
-
Low-density lipoprotein
- LPL:
-
Lipoprotein lipase
- MAPK:
-
Mitogen-activated protein kinase
- MCP-1:
-
Macrophage chemo attractant protein-1
- mTOR:
-
Mammalian target of rapamycin
- NADP:
-
Nicotinamide adenine dinucleotide phosphate
- NEFA:
-
Non-esterified fatty acid
- NFAT:
-
Nuclear factor of activated T cells
- NFκ-B:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- NO:
-
Nitric oxide
- NOXs:
-
NADPH oxidases
- NRF1:
-
Nuclear respiratory factor 1
- OXPHO:
-
Oxidative phosphorylation
- PAI-1:
-
Plasminogen activator inhibitor-1
- PFK2:
-
Phosphofructokinase 2
- PGC-1α:
-
PPAR-γ coactivator 1α
- PH:
-
Pleckstrin homology
- PI3K:
-
Phosphatidylinositol 3-kinase
- PKC:
-
Protein kinase C
- PKB/Akt:
-
Protein kinase B
- PPARs:
-
Peroxisome proliferator-activated receptors
- PTEN:
-
Phosphatase and tensin homolog
- PTP1B:
-
Protein tyrosine phosphatase 1B
- ROS:
-
Reactive oxygen species
- SHIP:
-
SH2-containing inositol 5′-phosphatase
- SOCS:
-
Suppressors of cytokine signaling
- SREBP:
-
Sterol regulatory element binding protein
- TAG:
-
Triacyl glycerol
- Tfam A:
-
Mitochondrial transcription factor A
- TLRs:
-
Toll-like receptors
- TNF-α:
-
Tumor necrosis factor-α
- UCP:
-
Uncoupling protein
- VAT:
-
Visceral adipose tissue
- VEGF:
-
Vascular endothelial growth factor
- VLDL:
-
Very low-density lipoprotein
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Acknowledgments
Prof. Sarita Gupta was a visiting scientist in Institute of Cardiovascular Sciences. Nathalia Bernardes and Danielle da Silva Dias were exchange students, under the Canada-Brazil Training program. Dr. Pawan Singal is the holder of the Dr. Naranjan S. Dhalla Chair in Cardiovascular Research supported by St. Boniface Hospital and Research Foundation.
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Patel, T.P., Rawal, K., Bagchi, A.K. et al. Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes. Heart Fail Rev 21, 11–23 (2016). https://doi.org/10.1007/s10741-015-9515-6
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DOI: https://doi.org/10.1007/s10741-015-9515-6