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Published in: Heart Failure Reviews 2/2019

01-03-2019

Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy

Authors: Brahmanaidu Parim, V. V. Sathibabu Uddandrao, Ganapathy Saravanan

Published in: Heart Failure Reviews | Issue 2/2019

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Diabetic complications are among the largely exigent health problems currently. Cardiovascular complications, including diabetic cardiomyopathy (DCM), account for more than 80% of diabetic deaths. Investigators are exploring new therapeutic targets to slow or abate diabetes because of the growing occurrence and augmented risk of deaths due to its complications. Research on rodent models of type 1 and type 2 diabetes mellitus, and the use of genetic engineering techniques in mice and rats have significantly sophisticated for our understanding of the molecular mechanisms in human DCM. DCM is featured by pathophysiological mechanisms that are hyperglycemia, insulin resistance, oxidative stress, left ventricular hypertrophy, damaged left ventricular systolic and diastolic functions, myocardial fibrosis, endothelial dysfunction, myocyte cell death, autophagy, and endoplasmic reticulum stress. A number of molecular and cellular pathways, such as cardiac ubiquitin proteasome system, FoxO transcription factors, hexosamine biosynthetic pathway, polyol pathway, protein kinase C signaling, NF-κB signaling, peroxisome proliferator-activated receptor signaling, Nrf2 pathway, mitogen-activated protein kinase pathway, and micro RNAs, play a major role in DCM. Currently, there are a few drugs for the management of DCM and some of them have considerable adverse effects. So, researchers are focusing on the natural products to ameliorate it. Hence, in this review, we discuss the pathogical, molecular, and cellular mechanisms of DCM; the current diagnostic methods and treatments; adverse effects of conventional treatment; and beneficial effects of natural product-based therapeutics, which may pave the way to new treatment strategies.
Literature
6.
go back to reference WHO (2016) Global report on diabetes, ISBN 978 92 4 156525 7 WHO (2016) Global report on diabetes, ISBN 978 92 4 156525 7
12.
go back to reference Khan JN, Wilmot EG, Leggate M (2014) Subclinical diastolic dysfunction in young adults with type 2 diabetes mellitus: a multiparametric contrast-enhanced cardiovascular magnetic resonance pilot study assessing potential mechanisms. Eur Heart J Cardiovasc Imaging 15:1263–1269. https://doi.org/10.1093/ehjci/jeu121 PubMedCrossRef Khan JN, Wilmot EG, Leggate M (2014) Subclinical diastolic dysfunction in young adults with type 2 diabetes mellitus: a multiparametric contrast-enhanced cardiovascular magnetic resonance pilot study assessing potential mechanisms. Eur Heart J Cardiovasc Imaging 15:1263–1269. https://​doi.​org/​10.​1093/​ehjci/​jeu121 PubMedCrossRef
24.
go back to reference Schinkel AF, Bax JJ, Valkema R, Elhendy A, van Domburg R, Vourvouri EC, Bountioukos MA, Krenning EP, Roelandt JR, Poldermans D (2003) Effect of diabetes mellitus on myocardial 18F-FDG SPECT using acipimox for the assessment of myocardial viability. J Nucl Med 44:877–883PubMed Schinkel AF, Bax JJ, Valkema R, Elhendy A, van Domburg R, Vourvouri EC, Bountioukos MA, Krenning EP, Roelandt JR, Poldermans D (2003) Effect of diabetes mellitus on myocardial 18F-FDG SPECT using acipimox for the assessment of myocardial viability. J Nucl Med 44:877–883PubMed
34.
35.
go back to reference Lakshmanan AP, Harima M, Suzuki K, Soetikno V, Nagata M, Nakamura T, Takahashi T, Sone H, Kawachi H, Watanabe K (2013) The hyperglycemia stimulated myocardial endoplasmic reticulum (ER) stress contributes to diabetic cardiomyopathy in the transgenic nonobese type 2 diabetic rats: a differential role of unfolded protein response (UPR) signaling proteins. Int J Biochem Cell Biol 45:438–447. https://doi.org/10.1016/j.biocel.2012.09.017 PubMedCrossRef Lakshmanan AP, Harima M, Suzuki K, Soetikno V, Nagata M, Nakamura T, Takahashi T, Sone H, Kawachi H, Watanabe K (2013) The hyperglycemia stimulated myocardial endoplasmic reticulum (ER) stress contributes to diabetic cardiomyopathy in the transgenic nonobese type 2 diabetic rats: a differential role of unfolded protein response (UPR) signaling proteins. Int J Biochem Cell Biol 45:438–447. https://​doi.​org/​10.​1016/​j.​biocel.​2012.​09.​017 PubMedCrossRef
52.
go back to reference Luo J, Wu S, Liu J, Li Y, Yang H, Kim T, Zhelyabovska O, Ding G, Zhou Y, Yang Y, Yang Q (2010) Conditional PPARgamma knockout from cardiomyocytes of adult mice impairs myocardial fatty acid utilization and cardiac function. Am J Transl Res 3:61–72PubMedPubMedCentral Luo J, Wu S, Liu J, Li Y, Yang H, Kim T, Zhelyabovska O, Ding G, Zhou Y, Yang Y, Yang Q (2010) Conditional PPARgamma knockout from cardiomyocytes of adult mice impairs myocardial fatty acid utilization and cardiac function. Am J Transl Res 3:61–72PubMedPubMedCentral
68.
go back to reference Andreadis EA, Katsanou PM, Georgiopoulos DX, Tsourous G, Yfanti G, Gouveri E, Diamantopoulos E (2009) The effect of metformin on the incidence of type 2 diabetes mellitus and cardiovascular disease risk factors in overweight and obese subjects the Carmos study. Exp Clin Endocrinol Diabetes 117:175–180. https://doi.org/10.1055/s-0028-1087177 PubMedCrossRef Andreadis EA, Katsanou PM, Georgiopoulos DX, Tsourous G, Yfanti G, Gouveri E, Diamantopoulos E (2009) The effect of metformin on the incidence of type 2 diabetes mellitus and cardiovascular disease risk factors in overweight and obese subjects the Carmos study. Exp Clin Endocrinol Diabetes 117:175–180. https://​doi.​org/​10.​1055/​s-0028-1087177 PubMedCrossRef
73.
go back to reference Kawasaki D, Kosugi K, Waki H, Yamamoto K, Tsujino T, Masuyama T (2007) Role of activated renin-angiotensin system in myocardial fibrosis and left ventricular diastolic dysfunction in diabetic patients–reversal by chronic angiotensin ii type 1a receptor blockade. Circ J 71:524–529. https://doi.org/10.1253/circj.71.524 PubMedCrossRef Kawasaki D, Kosugi K, Waki H, Yamamoto K, Tsujino T, Masuyama T (2007) Role of activated renin-angiotensin system in myocardial fibrosis and left ventricular diastolic dysfunction in diabetic patients–reversal by chronic angiotensin ii type 1a receptor blockade. Circ J 71:524–529. https://​doi.​org/​10.​1253/​circj.​71.​524 PubMedCrossRef
74.
go back to reference Westermann D, Rutschow S, Jager S, Linderer A, Anker S, Riad A, Unger T, Schultheiss HP, Pauschinger M, Tschope C (2007) Contributions of inflammation and cardiac matrix metalloproteinase activity to cardiac failure in diabetic cardiomyopathy: the role of angiotensin type 1 receptor antagonism. Diabetes 56:641–646. https://doi.org/10.2337/db06-1163 PubMedCrossRef Westermann D, Rutschow S, Jager S, Linderer A, Anker S, Riad A, Unger T, Schultheiss HP, Pauschinger M, Tschope C (2007) Contributions of inflammation and cardiac matrix metalloproteinase activity to cardiac failure in diabetic cardiomyopathy: the role of angiotensin type 1 receptor antagonism. Diabetes 56:641–646. https://​doi.​org/​10.​2337/​db06-1163 PubMedCrossRef
75.
77.
79.
go back to reference Nisbet JC, Sturtevant JM, Prins JB (2004) Metformin and serious adverse effects. Med J Aust 180:53–54PubMed Nisbet JC, Sturtevant JM, Prins JB (2004) Metformin and serious adverse effects. Med J Aust 180:53–54PubMed
86.
go back to reference Campbell RK, Cobble ME, Reid TS, Shomali ME (2010) Distinguishing among incretin-based therapies. Safety, tolerability, and nonglycemic effects of incretin-based therapies. J Fam Pract 59:20–27 Campbell RK, Cobble ME, Reid TS, Shomali ME (2010) Distinguishing among incretin-based therapies. Safety, tolerability, and nonglycemic effects of incretin-based therapies. J Fam Pract 59:20–27
117.
go back to reference Kalaivani A, Sathibabu Uddandrao VV, Brahmanaidu P, Saravanan G, Nivedha PR, Tamilmani P, Swapna K, Vadivukkarasi S (2017) Anti obese potential of Cucurbita maxima seeds oil: effect on lipid profile and histoarchitecture in high fat diet induced obese rats. Nat Prod Res. https://doi.org/10.1080/14786419.2017.1389939 Kalaivani A, Sathibabu Uddandrao VV, Brahmanaidu P, Saravanan G, Nivedha PR, Tamilmani P, Swapna K, Vadivukkarasi S (2017) Anti obese potential of Cucurbita maxima seeds oil: effect on lipid profile and histoarchitecture in high fat diet induced obese rats. Nat Prod Res. https://​doi.​org/​10.​1080/​14786419.​2017.​1389939
118.
120.
go back to reference Ghanshyam P, Chhayakanta P, Shankar MU et al (2012) Investigation of possible hypoglycemic and hypolipidemic effect of methanolic extract of Sesbania grandiflora. Int Res J Pharm 3:275–280 Ghanshyam P, Chhayakanta P, Shankar MU et al (2012) Investigation of possible hypoglycemic and hypolipidemic effect of methanolic extract of Sesbania grandiflora. Int Res J Pharm 3:275–280
121.
go back to reference Nandi MK, Garabadu D, Krishnamurthy S, Singh TD, Singh VP (2014) Methanolic fruit extract of Sesbania grandiflora exhibits anti-hyperglycemic activity in experimental type-2 diabetes mellitus model. Ann Biol Res 5:50–58 Nandi MK, Garabadu D, Krishnamurthy S, Singh TD, Singh VP (2014) Methanolic fruit extract of Sesbania grandiflora exhibits anti-hyperglycemic activity in experimental type-2 diabetes mellitus model. Ann Biol Res 5:50–58
125.
go back to reference Wang C, Aungi HH, Zhang B et al (2008) Chemopreventive effects of heat-processed Panax quinquefolius root on human breast cancer cells. Anticancer Res 28:2545–2552PubMedPubMedCentral Wang C, Aungi HH, Zhang B et al (2008) Chemopreventive effects of heat-processed Panax quinquefolius root on human breast cancer cells. Anticancer Res 28:2545–2552PubMedPubMedCentral
128.
go back to reference Erejuwa OO, Sulaiman SA, Ab Wahab MS, Sirajudeen KN, Salleh S, Gurtu S (2012) Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress. Oxidative Med Cell Longev 2012:374037. https://doi.org/10.1155/2012/374037 CrossRef Erejuwa OO, Sulaiman SA, Ab Wahab MS, Sirajudeen KN, Salleh S, Gurtu S (2012) Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress. Oxidative Med Cell Longev 2012:374037. https://​doi.​org/​10.​1155/​2012/​374037 CrossRef
130.
go back to reference Hiramatsu K, Tsuneyoshi T, Ogawa T, Morihara N (2016) Aged garlic extract enhances heme oxygenase-1 and glutamate–cysteine ligase modifier subunit expression via the nuclear factor erythroid 2-related factor 2-antioxidant response element signaling pathway in human endothelial cells. Nut Res 36:143–149. https://doi.org/10.1016/j.nutres.2015.09.018 CrossRef Hiramatsu K, Tsuneyoshi T, Ogawa T, Morihara N (2016) Aged garlic extract enhances heme oxygenase-1 and glutamate–cysteine ligase modifier subunit expression via the nuclear factor erythroid 2-related factor 2-antioxidant response element signaling pathway in human endothelial cells. Nut Res 36:143–149. https://​doi.​org/​10.​1016/​j.​nutres.​2015.​09.​018 CrossRef
Metadata
Title
Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy
Authors
Brahmanaidu Parim
V. V. Sathibabu Uddandrao
Ganapathy Saravanan
Publication date
01-03-2019
Publisher
Springer US
Published in
Heart Failure Reviews / Issue 2/2019
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI
https://doi.org/10.1007/s10741-018-9749-1

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