Cellular and Molecular Abnormalities in the Vascular Endothelium of Diabetes Mellitus

King, George L.; Shiba, Teruo; Oliver, Javier; Inoguchi, Toyoshi; Bursell, Sven Erik

doi:10.1146/annurev.med.45.1.179

Cited by 119 publications

(81 citation statements)

References 31 publications

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“…Hyperglycaemia also seems to have a causal role in vascular dysfunction but its mechanism is not clear. A number of hypotheses have been proposed including alteration of redox potentials, the sorbitol hypothesis and nonenzymatic glycation [29,74].…”

Section: R2mentioning

confidence: 99%

Advanced glycation end-products: a review

et al. 2001

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Diabetes is a common condition with multiple complications. There has been much work done to elaborate on the aetiology, prevention and treatment of diabetes related complications. The DCCT [1] and UKPDS [2] studies have emphasised the role of tight glucose control as being important in reducing diabetic microvascular disease in Type I (insulin-dependent) diabetes mellitus (DCCT) and Type II (non-insulin-dependent) diabetes mellitus (UKPDS). The relation between tight glucose control and macrovascular complications is, however, not clear [3]. Recently the importance of blood pressure control in reducing diabetic microvascular complications has been shown [4]. Apart from these factors, damage induced by hyperglycaemia involves a complex interaction between many influences including genetic predisposition, smoking, BMI, dyslipidaemia and alterations in coagulation factors [3]. The presence of advanced glycation end-products (AGE) is closely related to Diabetologia (2001) AbstractAdvanced glycation end-products are a complex and heterogeneous group of compounds that have been implicated in diabetes related complications. At present it is not known if they are the cause or the consequence of the complications observed. We discuss the chemistry of advanced glycated end-product formation and their patho-biochemistry particularly in relation to the diabetic microvascular complications of retinopathy, neuropathy and nephropathy as well as their role in the accelerated vasculopathy observed in diabetes. The concept of carbonyl stress as a cause for advanced glycated end-product toxicity is mentioned. We discuss alterations in the concentrations of advanced glycated end-products in the body, particularly in relation to changes occuring with age, diabetes and its complications such as nephropathy. Problems relating to current methods of advanced glycated end-product detection and measurement are highlighted including the lack of a universally established method of detection or unit of measurement. Agents used for the treatment of advanced glycated end-product accumulation are reviewed, with an emphasis on the results of the recent phase III trials using aminoguanidine and diabetes related complications. [Diabetologia (2001) 44: 129±146]Keywords Advanced glycated end-products, diabetes mellitus, microvascular disease, carbonyl stress, aminoguanidine.Corresponding author: Dr R. Singh MRCP (UK), FRACP, University Dept of Medicine, Royal Perth Hospital, PO Box X2213, Perth 6847, Western Australia Abbreviations: ESRD, End-stage renal disease; 3-DG, 3-deoxyglucosone; MGO, methylglyoxal; DOLD, deoxyglucosone-lysine dimer; MOLD, methyl glyoxal-lysine dimer; CML, N e -[carboxymethyl]-lysine; FFI, furoyl-furanyl imidazole; PTB, phenacyl thiozolium bromide; RAGE, receptor for AGE; NF-kB, nuclear factor-kB; VCAM-1, vascular cell adhesion molecule-1; ICAM-1, intracellular adhesion molecule-1; PECAM-1, platelet endothelial cell adhesion molecule-1; ELAM-1, endothelial leucocyte adhesion molecule-1; MSR, macrophage scavenger recepto...

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Section: R2mentioning

confidence: 99%

Advanced glycation end-products: a review

et al. 2001

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“…The previous assumption be supported by the hypothesis of King et al [42] , who reported that sorbitol is accumulated in the vascular and neuronal tissues in the retina of diabetic subjects. In addition, the degradation of sorbitol progresses relatively slowly, resulting in the accumulation of sorbitol inside cells.…”

Section: Discussionmentioning

confidence: 64%

Sorbitol-Induced Diabetic-Like Retinal Lesions in Rats: Microscopic Study

Ramadan¹

2007

American J. of Pharmacology and Toxicology

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Abstract:The present study investigated the sorbitol toxicity on the retinas of normal albino rats and founded by the light microscope that intra-peritoneal injection of Sorbitol (10-mg/kg-body weight per day) for 24 weeks produced similar diabetic like retinal lesions in these rats. The retinopathic effects of sorbitol injection affect retinal microvessels, pigment epithelium, neural retina and glial cells. Cytoplasmic vacuolation of the pigment epithelium and oedema of the neural retinal cells were evident. Microvascular abnormalities include thick-walled, elongated and dilated blood capillaries. The abnormal capillaries showed aneurysms and were occluded with deformed, fragmented, and adherent blood cells. Another finding was the pyknosis of glial cells. The present investigation concluded that sorbitol is toxic to the retinal tissue and it may play a role in the setup of diabetic retinopathy.

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“…Several investigators have shown that hyperglycaemia and the diabetic state induce a persistent activation of protein kinase C (PKC) in vascular tissues and in cultured vascular cells [10] and suggest that the activation of PKC may alter vascular functions in macro-and micro-vessels. As it has been reported that IL-8 gene expression is regulated by the PKC-dependent pathway [5], the persistent PKC activation by high glucose level may contribute to the increase a b m g RNA from AoEC after 2 days' culture was electrophoresed and transferred to a nylon membrane.…”

Section: Resultsmentioning

confidence: 99%

High glucose enhances the gene expression of interleukin-8 in human endothelial cells, but not in smooth muscle cells: possible role of interleukin-8 in diabetic macroangiopathy

et al. 1997

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Several large prospective epidemiological investigations have disclosed that coronary artery disease is the main cause of morbidity and death in patients with diabetes mellitus. The Multiple Risk Factor Intervention Trial [1] revealed that the mortality rate for coronary artery disease and cardiovascular disease such as cerebral infarction and arteriosclerosis obliterans was three times higher in diabetic men than in non-diabetic men.However, the exact cellular and molecular mechanism for increased risk of these atherosclerotic vascular diseases in diabetic patients remains unclear. Atherosclerosis is described as a response of the artery wall to initiating agents followed by the formation of the atherosclerotic plaque by multiple pathogenic mechanisms [2]. One critical pathological event in the atherosclerotic lesion is the migration of medial smooth muscle cells (SMC) to the intima where these cells proliferate. Various molecules regulating SMC growth are secreted from platelets, monocyte/macrophages, lymphocytes, endothelial cells, and SMC themselves. These cells, in concert with a damaged and/or "activated" endothelium, synthesize and release many kinds of growth factors and cytokines, which lead to the migration and proliferation of SMC, the recruitment of additional blood cells, and the accumulation of lipids. Among proinflammatory cytokines, tumour necrosis factor(TNF)-a, interleukin(IL)-1b, IL-6, and IL-8 are reported to be involved in the pathogenesis of atherosclerosis [3].

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Cellular and Molecular Abnormalities in the Vascular Endothelium of Diabetes Mellitus

Cited by 119 publications

References 31 publications

Advanced glycation end-products: a review

Advanced glycation end-products: a review

Sorbitol-Induced Diabetic-Like Retinal Lesions in Rats: Microscopic Study

High glucose enhances the gene expression of interleukin-8 in human endothelial cells, but not in smooth muscle cells: possible role of interleukin-8 in diabetic macroangiopathy

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