Aldose reductase gene is associated with diabetic macroangiopathy in Japanese Type 2 diabetic patients

Watarai, Atsuko; Nakashima, Eitaro; Hamada, Yoji; Watanabe, Genichi; Naruse, Keiko; Miwa, Koji; Kobayashi, Yoritoshi; Kawanishi, Hideki; Nakae, Mika; Hamajima, Nobuyuki; Sekido, Yoshitaka; Niwa, Toshifumi; Oiso, Yutaka; Nakamura, Jiro

doi:10.1111/j.1464-5491.2006.01946.x

Cited by 26 publications

(16 citation statements)

References 27 publications

(50 reference statements)

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“…All of their observations were improved by an AR inhibitor. The aforementioned previous studies, and the novel findings of Tang et al . and Vedantham et al .…”

Section: Pathogenesis Of Ischemic Cerebrovascular Disorders In Diabetesmentioning

confidence: 72%

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Pathogenesis and neuroimaging of cerebral large and small vessel disease in type 2 diabetes: A possible link between cerebral and retinal microvascular abnormalities

Umemura

Kawamura

Hotta

2016

J of Diabetes Invest

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Diabetes patients have more than double the risk of ischemic stroke compared with non‐diabetic individuals, and its neuroimaging characteristics have important clinical implications. To understand the pathophysiology of ischemic stroke in diabetes, it is important to focus not only on the stroke subtype, but also on the size and location of the occlusive vessels. Specifically, ischemic stroke in diabetes patients might be attributed to both large and small vessels, and intracranial internal carotid artery disease and small infarcts of the posterior circulation often occur. An additional feature is that asymptomatic lacunar infarctions are often seen in the basal ganglia and brain stem on brain magnetic resonance imaging. In particular, cerebral small vessel disease (SVD), including lacunar infarctions, white matter lesions and cerebral microbleeds, has been shown to be associated not only with stroke incidence, but also with the development and progression of dementia and diabetic microangiopathy. However, the pathogenesis of cerebral SVD is not fully understood. In addition, data on the association between neuroimaging findings of the cerebral SVD and diabetes are limited. Recently, the clinical importance of the link between cerebral SVD and retinal microvascular abnormalities has been a topic of considerable interest. Several clinical studies have shown that retinal microvascular abnormalities are closely related to cerebral SVD, suggesting that retinal microvascular abnormalities might be pathophysiologically linked to ischemic cerebral SVD. We review the literature relating to the pathophysiology and neuroimaging of cerebrovascular disease in diabetes, and discuss the problems based on the concept of cerebral large and small vessel disease.

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“…All of their observations were improved by an AR inhibitor. The aforementioned previous studies, and the novel findings of Tang et al . and Vedantham et al .…”

Section: Pathogenesis Of Ischemic Cerebrovascular Disorders In Diabetesmentioning

confidence: 72%

“…Previous studies by our group and others have suggested that hyperglycemia‐induced polyol pathway hyperactivity might, in part, play an important role in the development of diabetes atherosclerosis. Recently, Tang et al .…”

Section: Pathogenesis Of Ischemic Cerebrovascular Disorders In Diabetesmentioning

confidence: 83%

Pathogenesis and neuroimaging of cerebral large and small vessel disease in type 2 diabetes: A possible link between cerebral and retinal microvascular abnormalities

Umemura

Kawamura

Hotta

2016

J of Diabetes Invest

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“…In Japanese type 2 diabetic patients, genetic polymorphism of AR has been associated with diabetic macroangiopathy. Clearly, larger studies are warranted to establish the association between AR gene polymorphism and diabetic cardiovascular disease 60.…”

Section: Polymorphisms Of Ald2 and Risk Of Diabetic Complicationmentioning

confidence: 99%

Aldose Reductase and Cardiovascular Diseases, Creating Human-Like Diabetic Complications in an Experimental Model

Ramasamy

Goldberg

2010

Circulation Research

134

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Hyperglycemia and reduced insulin actions affect many biological processes. One theory is that aberrant metabolism of glucose via several pathways including the polyol pathway causes cellular toxicity. Aldose reductase (AR) is a multifunctional enzyme that reduces aldehydes. Under diabetic conditions AR converts glucose into sorbitol, which is then converted to fructose. This article reviews the biology and pathobiology of AR actions. AR expression varies considerably among species. In humans and rats, the higher level of AR expression is associated with toxicity. Flux via AR is increased by ischemia and its inhibition during ischemia reperfusion reduces injury. However, similar pharmacological effects are not observed in mice unless they express a human AR transgene. This is because mice have much lower levels of AR expression, probably insufficient to generate toxic byproducts. Human AR expression in LDL receptor knockout mice exacerbates vascular disease, but only under diabetic conditions. In contrast, a recent report suggests that genetic ablation of AR increased atherosclerosis and increased hydroxynonenal in arteries. It was hypothesized that AR knockout prevented reduction of toxic aldehydes. Like many in vivo effects found in genetically manipulated animals, interpretation requires the reproduction of human-like physiology. For AR, this will require tissue specific expression of AR in sites and at levels that approximate those in humans. (Circ Res. 2010;106:1449-1458.)Key Words: diabetes Ⅲ macrovascular disease Ⅲ atherosclerosis Ⅲ fructose D uring the past decade, studies in genetically modified mice have been used to define processes that contribute to atherosclerosis. Alterations in macrophage and endothelial cell biology by genetic overexpression or deletion can greatly modify vascular lesion extent and also the composition of plaques; these latter effects are viewed as ways to uncover processes leading to plaque instability. Although many processes might alter inflammation and hence lesion extent and complexity, the observation that diabetes/hyperglycemia/ insulin-deficiency alone does not always result in greater Original received November 18, 2009; revision received April 7, 2010; accepted April 8, 2010. From the Departments of Surgery (R.R.) and Medicine (I.J.G.), Columbia University College of Physicians and Surgeons, New York. Correspondence to Dr Ravichandran Ramasamy, Department of Surgery, Columbia University, 630 West 168th St, Black Building 1706a, New York, NY 10032. E-mail rr260@columbia.edu © 2010 American Heart Association, Inc. Many genes are expressed in rodent tissues at levels that are disproportionate to those in humans, and these lead to changes in physiology and response to drugs that are totally different from those of humans. A case in point is the expression of peroxisome proliferator-activated receptor (PPAR) transcription factors. Rodent livers express much higher levels of both PPAR␣ and PPAR␥ than do humans. 2 For this reason, whereas activation of PPAR␣ in rats...

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“…However, it has also been reported that the C-106T polymorphism may contribute to an early development of neurophysiologic deterioration in DM2 patients (Sivenius et al, 2004b). In Japanese DM2 patients, the C-106T variant was also associated with diabetic macroangiopathy, were the CT or TT genotype showed association with increased risk of stroke (Watarai et al, 2006).…”

Section: Aldose Reductasementioning

confidence: 99%

Genetics of Endothelial Damage Associated to Diabetes Mellitus Type 2

Garcı́a¹,

Wolff²,

Araya³

et al. 2011

Medical Complications of Type 2 Diabetes

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Aldose reductase gene is associated with diabetic macroangiopathy in Japanese Type 2 diabetic patients

Cited by 26 publications

References 27 publications

Pathogenesis and neuroimaging of cerebral large and small vessel disease in type 2 diabetes: A possible link between cerebral and retinal microvascular abnormalities

Pathogenesis and neuroimaging of cerebral large and small vessel disease in type 2 diabetes: A possible link between cerebral and retinal microvascular abnormalities

Aldose Reductase and Cardiovascular Diseases, Creating Human-Like Diabetic Complications in an Experimental Model

Genetics of Endothelial Damage Associated to Diabetes Mellitus Type 2

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