Abstract:
:The incidence of mortality from cardiovascular diseases in higher in diabetic patients. The cause of this accelerated cardiovascular disease is multifactorial and, although atherosclerotic cardiovascular disease in association with well-defined risk factors has an influence on morbidity and mortality in diabetics, myocardial cell dysfunction independent of vascular defects have also been defined. We postulate that these adverse cardiac effects could presumably result as a consequence of the following sequence of events. Major abnormalities in myocardial carbohydrate and lipid metabolism occur as a result of insulin deficiency. These changes are closely linked to the accumulation of various acylcarnitine and coenzyme derivatives. Abnormally high amounts of metabolic intermediates could cause disturbances in calcium homeostasis either directly or indirectly through structural and functional subcellular membrane alterations. Over time, chronic abnormalities such as reduced myosin ATPase activity, decreased ability of the sarcoplasmic reticulum to take up calcium as well as depression of other membrane enzymes such as Na(+)-K+ ATPase and Ca(2+)-ATPase leads to changes in calcium homeostasis and eventually to cardiac dysfunction. More importantly from the point of view of pharmacological intervention, during the initial stages, acute disturbances in both the glucose and FFA oxidative pathways may provide the initial biochemical lesion from which further events ensue. Thus therapies which target these metabolic aberrations in the heart during the early stages of diabetes, in effect, can potentially delay or impede the progression of more permanent sequelae which could ensue from otherwise uncontrolled derangements in cardiac metabolism. There is little dispute that an attempt should be made to lower raised plasma triglyceride and FFA levels. This would decrease the heart's reliance on fatty acids and, hence, overcome the fatty acid inhibition of myocardial glucose utilization. In this regard, the likely application of fatty acid oxidation inhibitors (CPT inhibitors, beta-oxidation inhibitors, sequestration of mitochondrial CoA) is also apparent.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Rodrigues B,Cam MC,McNeill JHdoi
10.1016/s0022-2828(08)80016-8subject
Has Abstractpub_date
1995-01-01 00:00:00pages
169-79issue
1eissn
0022-2828issn
1095-8584pii
S0022-2828(08)80016-8journal_volume
27pub_type
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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更新日期:1997-08-01 00:00:00
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更新日期:1991-04-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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更新日期:1998-02-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:1984-10-01 00:00:00
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更新日期:2003-06-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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更新日期:1998-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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更新日期:2017-08-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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更新日期:2016-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
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更新日期:2012-04-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:2008-05-01 00:00:00