Correlation between Metabolic and Histopathological Changes in the Myocardium of the KK Mouse. Effect of Diltiazem on the Diabetic Heart.

Shimada, Toshimi

doi:10.1536/ihj.34.617

Cited by 6 publications

(4 citation statements)

References 19 publications

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“…Continuous muscular activity may lead to depletion of oxygen and shift toward anaerobic LDH isoenzymes . Hence, the ratio of [LDH‐I+LDH‐II/LDH‐IV+LDH‐V] has been utilized as the index of aerobic metabolism of muscles . Moreover, as this ratio also correlates with degree of MF , it can be utilized to study the pathogenesis and malignant transformation of OSF.…”

Section: Discussionmentioning

confidence: 99%

“…While several studies have implicated total LDH in the pathogenesis of OSF , surprisingly, very few have studied specific isoforms of LDH . Among these isoforms, LDH‐I, LDH‐II, and LDH‐III are the aerobic isoforms, while LDH‐IV and LDH‐V are the anaerobic isoforms . Furthermore, the former are inhibited by pyruvate and lactate, while latter are not .…”

Section: Discussionmentioning

confidence: 99%

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Limited mouth opening in oral submucous fibrosis: reasons, ramifications, and remedies

Sharma

Radhakrishnan

2016

J Oral Pathology Medicine

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Limited mouth opening (LMO) in oral submucous fibrosis (OSF) has been attributed to both the submucosal and muscle fibrosis (MF). While reflectory trismus was proposed before as an auxiliary mechanism by another group, the stretch-mediated muscle damage (MSD), histopathological changes in blood vessels (such as endothelial dysfunction, endothelial hypertrophy, and endarteritis obliterans), and upregulated anaerobic isoforms of lactate dehydrogenase (LDH) have been proposed by us as complementary events leading to MF. Additionally, the amount of hypoxia-mediated upregulation of anaerobic isoforms of LDH determines the extent of MF. Radiotherapy (RT)-mediated release of reactive oxygen species causes vascular damage thereby worsening hypoxia. While the alteration in LDH levels secondary to hypoxia enhances fibrosis, RT worsens it. Oral squamous cell carcinoma occurring in the background of OSF is an absolute contraindication for RT as it augurs unfavorable prognosis. An algorithm to demonstrate this with evidence is clearly depicted. The role of HIF-1α in the progression of OSF and its malignant transformation, and the consideration of hyperbaric oxygen therapy as a therapeutic remedy in OSF are underscored.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Limited mouth opening in oral submucous fibrosis: reasons, ramifications, and remedies

Sharma

Radhakrishnan

2016

J Oral Pathology Medicine

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“…Diltiazem showed possible suppression of muscle hypertrophy, degeneration and fibrosis caused by hyperglycemia in animal T1D models [114]. Early studies with verapamil demonstrated marked improvement of myosin/myofibrillary ATPase and SERCA activity in ventricular tissue of STZ induced T1D animals.…”

Section: Treatment Strategies For Dcmmentioning

confidence: 99%

Metabolic dysfunction in diabetic cardiomyopathy

et al. 2013

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Diabetic cardiomyopathy (DCM) is defined as cardiac disease independent of vascular complications during diabetes. The number of new cases of DCM is rising at epidemic rates in proportion to newly diagnosed cases of diabetes mellitus (DM) throughout the world. DCM is a heart failure syndrome found in diabetic patients that is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction, occurring in the absence of hypertension and coronary artery disease. DCM and other diabetic complications are caused in part by elevations in blood glucose and lipids, characteristic of DM. Although there are pathological consequences to hyperglycemia and hyperlipidemia, the combination of the two metabolic abnormalities potentiates the severity of diabetic complications. A natural competition exists between glucose and fatty acid metabolism in the heart that is regulated by allosteric and feedback control and transcriptional modulation of key limiting enzymes. Inhibition of these glycolytic enzymes not only controls flux of substrate through the glycolytic pathway, but also leads to the diversion of glycolytic intermediate substrate through pathological pathways, which mediate the onset of diabetic complications. The present review describes the limiting steps involved in the development of these pathological pathways and the factors involved in the regulation of these limiting steps. Additionally, therapeutic options with demonstrated or postulated effects on DCM are described.

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“…12 KK/HlJ mice have a strong tendency to develop type 2 diabetes (T2D) in response to certain dietary regimens (eg, high-fat diet) and aging. 14 Diabetic nephropathy (characterized by increased kidney weight, albuminuria, and proteinuria), 25,26 interstitial fibrotic heart lesions, 29 and corneal degeneration 13,21 accompany the hyperglycemia if not treated by therapeutic interventions.…”

mentioning

confidence: 99%

Phenotypic Characterization of the KK/HlJ Inbred Mouse Strain

et al. 2013

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Detailed histopathological diagnoses of inbred mouse strains are important for interpreting research results and defining novel models of human diseases. The aim of this study was to histologically detect lesions affecting the KK/HlJ inbred strain. Mice were examined at 6, 12, and 20 months of age and near natural death (ie, moribund mice). Histopathological lesions were quantified by percentage of affected mice per age group and sex. Predominant lesions were mineralization, hyperplasia, and fibro-osseous lesions. Mineralization was most frequently found in the connective tissue dermal sheath of vibrissae, the heart, and the lung. Mineralization was also found in many other organs but to a lesser degree. Hyperplasia was found most commonly in the pancreatic islets, and fibro-osseous lesions were observed in several bones. The percentage of lesions increased with age until 20 months. This study shows that KK/HlJ mice demonstrate systemic aberrant mineralization, with greatest frequency in aged mice. The detailed information about histopathological lesions in the inbred strain KK/HlJ can help investigators to choose the right model and correctly interpret the experimental results.

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Correlation between Metabolic and Histopathological Changes in the Myocardium of the KK Mouse. Effect of Diltiazem on the Diabetic Heart.

Cited by 6 publications

References 19 publications

Limited mouth opening in oral submucous fibrosis: reasons, ramifications, and remedies

Limited mouth opening in oral submucous fibrosis: reasons, ramifications, and remedies

Metabolic dysfunction in diabetic cardiomyopathy

Phenotypic Characterization of the KK/HlJ Inbred Mouse Strain

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