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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Concentrations of pentosidine, an advanced glycation end product, are increased in aging, diabetes mellitus, and uremia. Using HPLC with column switching, we developed a direct method of measuring pentosidine in urine and serum. We inject the sample directly onto a gel-filtration precolumn, select ("heart-cut") the eluate fraction containing pentosidine, and introduce this fraction into a reversed-phased column by use of a switching valve. The recovery rate of the complete method was 97.7-99.9%. The intraassay CV was 5.7%, and the interassay CV was 5.8%. The calibration curve showed significant linearity (r = 0.998, P = 0.0001). We examined urinary concentrations of pentosidine in 12 diabetic patients (mean +/- SD, 8.7 +/- 2.3 micromol/mol of creatinine), 32 patients with chronic renal failure (CRF; 36.1 +/- 39.0), 19 osteoporotic patients (7.9 +/- 5.3), and 29 healthy control subjects (5.2 +/- 2.3). In CRF, urinary pentosidine in the patients undergoing hemodialysis was significantly higher than in CRF patients not being treated by hemodialysis (mean, 58.1 vs 18.2; P <0.001). Also, concentrations of urinary and serum pentosidine were significantly correlated (r = 0.797, P = 0.0011). Because this method does not require pretreatment of samples, it is convenient and useful for measuring urinary and serum pentosidine.
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PMID:Direct quantification of pentosidine in urine and serum by HPLC with column switching. 878 1

Cross-linking of proteins by sugars is thought to be involved in the pathogenesis of a variety of disorders associated with diabetes and aging; however, the molecular mechanisms involved in this process are not well understood. A new, general method for cross-link analysis, using precolumn derivatization with the reagent diphenylborinic acid (DPBA), was applied to the problem of detection and characterization of Maillard (sugar-derived) cross-links. DPBA analysis of reaction mixtures containing ribose, lysine, and arginine showed the presence of the Maillard cross-link pentosidine, along with a novel cross-link which was also found in acid hydrolyzates of ribose-treated proteins. Evidence is presented that this cross-link and pentosidine are the major acid-stable fluorescent cross-links formed by ribose with basic amino acids. Since it was determined that the new cross-link is derived from two lysine residues and at least one pentose per molecule, it was named penK2. PenK2 was found to be identical, by three different methods of chromatographic analysis, to the Maillard product "LM1', which was isolated from cataractous lens by Nagaraj and Monnier, but not yet structurally characterized (Biochim. Biophys. Acta 1116, (1992) 34-42).
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PMID:A comprehensive survey of the acid-stable fluorescent cross-links formed by ribose with basic amino acids, and partial characterization of a novel Maillard cross-link. 884 75

Blood glucose control plays a prominent role in the aetiology of diabetic complications. Recent data support the hypothesis that non-enzymatic pathways (glycation and oxidation) are involved in the pathogenesis of tissue damage in diabetes mellitus. In this study the level of pentosidine, a marker of glycation, and the intensity of collagen-linked fluorescence glycation (370/440 and 335/385 nm) and oxidation-related (356/460 and 390/460 nm), have been examined in spontaneously diabetic rats with good and poor glycaemic control. Pentosidine increased dramatically in rats with poor control, and slightly in those with good control. At the end of the study, after 6 months of diabetes, pentosidine levels were 13 +/- 5 and 2.1 +/- 0.5 pmol/mg collagen, respectively (control rats: 1.1 +/- 0.1 pmol/mg collagen). A similar pattern was observed for both glycation or oxidation-related fluorescence. The group of rats with poor control always showed elevated average values when compared to rats with good control, with a relative increase of over 200%. The results emphasize the role of good glycaemic control in preventing the growth of glycation or oxidation end-products in collagen. On comparison between the general mean level of all glycated haemoglobin and the mean pentosidine level of the three groups, a very good exponential correlation was found (r = 0.993, p < 0.001). The fluorescence values presented a less strong relationship, but a correlation with glycaemic control was still present. If the post-translational modifications of proteins play a leading role in the pathogenesis of complications it is possible to conclude that strict glycaemic control, obtained by accurate insulin therapy can prevent them by inhibiting the non-enzymatic modification of proteins and delaying their accumulation in collagen. The therapeutic implications are obvious.
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PMID:Good glycaemic control reduces oxidation and glycation end-products in collagen of diabetic rats. 896 Aug 24

We examined the effects of aminoguanidine and methylguanidine on vascular dysfunction, glomerular structural changes, and indexes of early and late nonenzymatic glycation in 7-month streptozotocin-induced diabetic rats. Kidney weight, glomerular volume, fractional mesangial volume, glomerular capillary basement membrane width, and urinary albumin excretion were increased in diabetic rats. Diabetes also 1) increased vascular albumin permeation twofold in retina, sciatic nerve, aorta, skin, and kidney; 2) decreased renal collagenase-soluble collagen; 3) increased collagen-associated fluorescence in kidney and skin but not in aorta; and 4) increased glycated hemoglobin levels and aortic pentosidine levels. Aminoguanidine reduced albuminuria by 70% after 4 months, and both guanidines 1) normalized aortic pentosidine levels and renal collagenase-soluble collagen, 2) had no effect on glycated hemoglobin levels or collagen-associated fluorescence (in aorta, kidney, or skin), and 3) had little or no effect on regional albumin permeation. These discordant effects of aminoguanidine on diabetes-induced vascular changes versus parameters of nonenzymatic glycation are consistent with a multifactorial pathogenesis of diabetic complications, including roles for metabolic imbalances independent of nonenzymatic glycation. To the extent that glomerular matrix accumulation and increased regional albumin permeation in chronically diabetic rats are sequelae of nonenzymatic glycation, these findings point to an important role for early glycation reactions and products.
Diabetes 1997 Jan
PMID:Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats. 897 Oct 88

The advanced glycation end-product, pentosidine, was measured in plasma proteins and skin collagen before and after kidney and kidney-pancreas transplantation in order to determine the relationship between plasma and tissue levels and to characterize the pattern of change in pentosidine levels after correction of hyperglycemia and/or renal failure. The content of pentosidine in skin collagen was higher than that in plasma proteins both before and after transplantation. However, there was no correlation between plasma and skin pentosidine levels. Prior to transplantation, the content of pentosidine in skin collagen was related to the duration of dialytic therapy, presence of diabetes mellitus, age, and female gender. Following transplantation, plasma pentosidine levels were inversely correlated with glomerular filtration rate (r = 0.64; p < 0.01). While plasma pentosidine levels consistently decreased after transplantation, levels in skin collagen increased in 10 of 13 patients, including 5 of 6 recipients of kidney-pancreas transplants. Our results indicate that tissue levels of pentosidine persist for long periods of time after kidney or kidney-pancreas transplantation, despite consistent decreases in levels measured in plasma proteins. The observed increase in tissue pentosidine levels in a majority of patients suggests that formation of advanced glycation end-products may continue after otherwise successful kidney or kidney-pancreas transplantation.
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PMID:Disparate changes in plasma and tissue pentosidine levels after kidney and kidney-pancreas transplantation. 899 81

In this article we review recent progress and controversies relating to three areas of the field of advanced glycosylation end-products (AGE). A controversy exists as to whether pyrraline, an AGE detectable by immunohistochemistry in kidneys from patients with renal failure, exists in vivo. Recent data from the authors' laboratory revealed that pyrraline is present in alkaline or protease digests from human skin and plasma. However, the amounts are very low and pyrraline was found to undergo further reactions to form an ether with itself (dipyrraline) as well as a thioether with cysteine. This high reactivity of pyrraline may explain the difficulty of quantitating it accurately in biological material. In contrast, the glycoxidation products carboxymethyllysine (CML) and pentosidine are stable, very resistant to acid hydrolysis and easy to quantitate. They are present in elevated concentrations in the extracellular matrix in diabetes mellitus and ageing. In the diabetic human lens, CML is not elevated, in contrast to pentosidine, suggesting a different mechanism of formation. Recent data in diabetic dogs have shown that pentosidine is elevated only in lenses from poorly controlled dogs, in contrast to LM-1, a fluorophore thought to arise from ascorbate. Further studies are needed to clarify the intracellular mechanism of glycoxidation. The greatest concentrations of AGEs and glycoxidation products are found in patients with end-stage renal disease, and they are almost completely normalized by renal transplantation. Comparison of peritoneal dialysis (PD) with haemodialysis (HD) showed that PD is associated with lower plasma protein pentosidine, possibly due to selective transport of pentosidine-rich protein across the peritoneal wall. Fractionation of plasma proteins from ESRD patients by size showed that 90% of pentosidine is linked to HMW protein and 1-2% is in free form. The mechanism of accelerated glycoxidation in ESRD is still not understood.
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PMID:Structure of advanced Maillard reaction products and their pathological role. 904 2

The amount of advanced glycation end-products (AGE) in tissue proteins increases in diabetes mellitus, and the concentration of a subclass of AGEs, known as glycoxidation products, also increases with chronological age in proteins. The rate of accumulation of glycoxidation products is accelerated in diabetes and age-adjusted concentrations of two glycoxidation products, N epsilon-(carboxymethyl)lysine (CML) and pentosidine, correlate with the severity of complication in diabetic patients. Although AGEs and glycoxidation products are implicated in the development of diabetic complications, these compounds are present at only trace concentrations in tissue proteins and account for only a fraction of the chemical modifications in AGE proteins prepared in vitro. The future of the AGE hypothesis depends on the chemical characterization of a significant fraction of the total AGEs in tissue proteins, a quantitative assessment of their effects on protein structure and function, and an assessment of their role as mediators of biological responses. In this manuscript we describe recent work leading to characterization of new AGEs and glycoxidation products. These compounds include: (1) the imidazolone adduct formed by reaction of 3-deoxyglucosone with arginine residues in protein; (2) N epsilon-(carboxyethyl)lysine, an analogue of CML formed on reaction of methylglyoxal with lysine; (3) glyoxal-lysine dimer; and (4) methyl-glyoxal-lysine dimer, which are imidazolium crosslinks formed by reaction of glyoxal or methylglyoxal with lysine residues in protein. The presence of 3-deoxyglucosone, methylglyoxal and glyoxal in vivo and the formation of the above AGEs in model carbonyl-amine reaction systems suggests that these AGEs are also formed in vivo and contribute to tissue damage resulting from the Maillard reaction.
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PMID:New biomarkers of Maillard reaction damage to proteins. 904 6

Many antioxidants have been found in spices and herbs, and some of them are well known as strong scavengers of active oxygen radicals. We have isolated active products, which markedly inhibited the formation of malondialdehyde (MDA from 2-deoxyribose and the hydroxylation of benzoate with the hydroxyl radical, from methanol extracts of allspice and clove. Pimentol from allspice, and biflorin and its isomer, abbreviated as clove3, from clove were identified as the active principles. These revealed strong activity as hydroxyl radical scavengers at a concentration of 2.0 microM. The antioxidative activities in an in vitro model system involving the rabbit erythrocyte membrane ghost were as strong as those of alpha-tocopherol at 200 microM. Such advanced glycation end products (AGE) as pentosidine are biomarkers of diabetes mellitus, and active oxygens have been suggested to be involved in the formation of AGE. The above-mentioned free radical scavengers effectively inhibited the formation of pentosidine in a model system of N alpha-t-butoxycarbonyl-fructoselysine and N alpha-t-butoxycarbonyl-arginine.
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PMID:Spice constituents scavenging free radicals and inhibiting pentosidine formation in a model system. 905 63

It has been hypothesized that advanced Maillard reaction in vivo could explain some of the age- and diabetes-related changes. Furthermore, involvement of the Maillard reaction with Alzheimer's disease has also been suggested, as advanced glycation end products, such as pyrraline and pentosidine, were demonstrated to localize in lesions of the disease. Although aminoguanidine has been studied extensively and established as an inhibitor of the Maillard reaction, other candidates have not been investigated thoroughly. In the present study, we examined the inhibitory effect of tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone], an antidementia drug, on the Maillard reaction. Tenilsetam inhibited glucose- and fructose-induced polymerization of lysozyme in a concentration-dependent manner in vitro. Reduced enzymatic digestibility of collagen incubated with 100 mM glucose for 4 weeks was also restored to a control level by coincubation with 100 mM tenilsetam. To determine whether tenilsetam inhibits the Maillard reaction in vivo, streptozotocin-induced diabetic rats were treated with tenilsetam (50 mg/kg x day). Elevated levels of advanced glycation end-product-derived fluorescence and pyrraline in renal cortex and aorta of diabetic rats were suppressed by the administration of tenilsetam for 16 weeks. These inhibitory effects of this agent on advanced glycation in diabetic rats suggested its potential therapeutic role in controlling diabetic complications.
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PMID:Inhibitory effects of tenilsetam on the Maillard reaction. 911 83

Nonenzymatic glycosylation (glycation) of proteins, often referred to as the Maillard reaction, has been proposed to play a role in age and diabetes-related processes by forming protein and DNA adducts and cross-links. These cross-links may contribute to erectile dysfunction by scavenging nitric oxide, which is needed for erection. As the basis for a possible role of the advanced Maillard reaction in age-related erectile dysfunction, we investigated the presence of the specific advanced glycation endproduct (AGE) pentosidine in penile corpus cavernosum tissue and penile tunica albuginea tissue as a function of age. A total of 23 penile tissue specimens were obtained at autopsy, from which 19 samples of tunica albuginea and 21 samples of corpus cavernosum were derived. In addition, 13 penile corporal and tunical specimens were procured at the time of insertion of a penile prosthesis, from which 12 tunica albugineal specimens and 10 samples of corpus cavernosum were derived. Collagen was extracted with acetic acid and pepsin digestion, and the final insoluble collagen product was acid-hydrolyzed with 6 N HCL for 24 h at 110 degrees C. Pentosidine was quantified by high-performance liquid chromatography using a reverse-phase column. The level of pentosidine (expressed in picomoles per milligram of insoluble collagen) was found to increase with age in cadaver as well as living penile corporal and tunical albugineal tissues. Best-fit analysis revealed an exponential increase in both types of cadaver penile tissue, with regression equations of y = 15.29 x 10(9.9e-3x), R2 = 0.79, being obtained in the tunica and y = 13.2 x 10(7.63e-3x), R2 = 0.56, in the corpora. These correspond to 6- and 4-fold increases in pentosidine levels from puberty to the age of 100 years (P < 0.05), respectively. Mean pentosidine levels were higher in the tunica than in the corpora. Comparison of pentosidine levels in the tunica versus the corpora revealed a weakly linear correlation (y = 24.88 + 1.08x, R2 = 0.32). Levels in the tunical and corporal specimens from the living human specimens fell with the predicted confidence intervals of the cadaveric tissue. Tunical specimens from patients who underwent repair or revision of a previously inserted penile prosthesis had very low levels of pentosidine. The exponential age-related increase in pentosidine observed in both types of penile tissue suggests an impairment of collagen turnover, which could be related to the advanced glycation reaction in aging. It is not known whether pentosidine itself is directly associated with erectile dysfunction, but its formation is usually accompanied by extensive tissue modification. Formation of advanced Maillard reaction products, which is greatly accelerated in aging, diabetes, and uremia, could contribute to erectile dysfunction in these syndromes.
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PMID:Age-related increase in an advanced glycation end product in penile tissue. 911 57


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