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Heart Failure Reviews

, Volume 21, Issue 1, pp 11–23 | Cite as

Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes

  • Tushar P. Patel
  • Komal Rawal
  • Ashim K. Bagchi
  • Gauri Akolkar
  • Nathalia Bernardes
  • Danielle da Silva Dias
  • Sarita Gupta
  • Pawan K. Singal
Article

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.

Keywords

Insulin resistance CVD Dyslipidemia Metabolic syndrome Oxidative stress Inflammation 

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

Notes

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.

Compliance with ethical standards

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Tushar P. Patel
    • 1
  • Komal Rawal
    • 1
  • Ashim K. Bagchi
    • 2
  • Gauri Akolkar
    • 2
  • Nathalia Bernardes
    • 2
  • Danielle da Silva Dias
    • 2
  • Sarita Gupta
    • 1
  • Pawan K. Singal
    • 2
  1. 1.Molecular Endocrinology and Stem Cell Research Lab, Department of Biochemistry, Faculty of ScienceThe Maharaja Sayajirao University of BarodaVadodaraIndia
  2. 2.Department of Physiology and Pathophysiology, Faculty of Health Sciences, St. Boniface Research Centre, Institute of Cardiovascular SciencesUniversity of ManitobaWinnipegCanada

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