Diabetic late complications: Will aldose reductase inhibitors or inhibitors of advanced glycosylation endproduct formation hold promise?

Boel, Esper; Selmer, Johan; Flodgaard, Hans; Jensen, Tonny

doi:10.1016/1056-8727(94)00025-j

Cited by 54 publications

(35 citation statements)

References 234 publications

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“…Using radioreceptor methodology, arterial wall AGE have been measured in autopsy samples from subjects with or without diabetes and renal disease [25]. The authors reported the highest concentrations of AGE in diabetic subjects with ESRD (21.3 U/mg protein), followed by diabetic subjects without renal disease (14.5 U/mg protein).…”

Section: Age Concentrations In Diabetes Chronological Age and Renal mentioning

confidence: 99%

“…Under normal conditions advanced glycated haemoglobin (Hb-AGE) accounts for 0.42 % of circulating haemoglobin but this increases to 0.75 % in diabetic subjects [25]. In a phase I clinical trial, 1200 mg a day of aminoguanidine reduced Hb-AGE by 28 % after 28 days in subjects with diabetes (Type I and Type II), for an average of 20 years.…”

Section: Age Concentrations In Diabetes Chronological Age and Renal mentioning

confidence: 99%

“…Similarly, it has been estimated that under normal conditions several milligrams of 3-DG are produced a day, and it is readily detoxified to 3-deoxy fructose and excreted in the urine [92]. The concentrations of 3-DG as measured by HPLC, has been shown to be 314 ng/ml in control subjects, 778 ng/ml in uncomplicated diabetes, and 1235 ng/ml in diabetics with renal disease (defined as a urinary albumin excretion rate of > 200 mg a day) [25].…”

Section: Age Concentrations In Diabetes Chronological Age and Renal mentioning

confidence: 99%

“…Glycation of haemoglobin forms HbA 1 c which has been described as an Amadori product [25] but it is not an AGE [49]. It is an indicator of glycaemia from the preceding 6 to 12 weeks, whereas advanced glycation reflects a process that can occur over a longer period.…”

Section: Formation and Structure Of Agementioning

confidence: 99%

“…Structural components of the connective tissue matrix or basement membrane, such as collagen, are prime targets but can also include myelin, complement C3, tubulin, plasminogen activator and fibrinogen [20,25]. In uraemia, however, which is associated with very high concentrations of AGE accumulation, even shorter lived compounds such as lipid constituents and nucleic acids are affected [26].…”

Section: Formation and Structure Of Agementioning

confidence: 99%

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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: Age Concentrations In Diabetes Chronological Age and Renal mentioning

confidence: 99%

Section: Age Concentrations In Diabetes Chronological Age and Renal mentioning

confidence: 99%

Section: Age Concentrations In Diabetes Chronological Age and Renal mentioning

confidence: 99%

Section: Formation and Structure Of Agementioning

confidence: 99%

Section: Formation and Structure Of Agementioning

confidence: 99%

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Advanced glycation end-products: a review

et al. 2001

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Protective role of zinc in liver damage in experimental diabetes demonstrated via different biochemical parameters

Saçan

Türkyılmaz

Bayrak

et al. 2020

J Biochem & Molecular Tox

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Diabetes mellitus is a serious worldwide metabolic disease, which is accompanied by hyperglycaemia and affects all organs and body system. Zinc (Zn) is a basic cofactor for many enzymes, which also plays an important role in stabilising the structure of insulin. Liver is the most important target organ after pancreas in diabetic complications. In this study, we aimed to investigate the protective role of Zn in liver damage in streptozotocin (STZ)‐induced diabetes mellitus. There are four experimental groups of female Swiss albino rats: group I: control; group II: control + ZnSO4; group III: STZ‐induced diabetic animals and group IV: STZ‐diabetic + ZnSO4. To induce diabetes, STZ was injected intraperitoneally (65 mg/kg). ZnSO4 (100 mg/kg) was given daily to groups II and IV by gavage for 60 days. At the end of the experiment, rats were killed under anaesthesia and liver tissues were collected. In the diabetic group, hexose, hexosamine, fucose, sialic acid levels, arginase, adenosine deaminase, tissue factor activities and protein carbonyl levels increased, whereas catalase, superoxide dismutase, glutathione‐S‐transferase, glutathione peroxidase, glutathione reductase and Na+/K+‐ATPase activities decreased. The administration of Zn to the diabetic group reversed all the negative effects/activities. According to these results, we can suggest that Zn has a protective role against STZ‐induced diabetic liver damage.

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