Imidazolone, a novel advanced glycation end product, is present at high levels in kidneys of rats with streptozotocin‐induced diabetes

Niwa, Toshimitsu; Katsuzaki, Tomoyuki; Ishizaki, Y; Hayase, Fumitaka; Miyazaki, Takashi; Uematsu, Toshihiko; Tatemichi, Noriyuki; Takei, Yoshiyuki

doi:10.1016/s0014-5793(97)00362-1

Cited by 56 publications

(30 citation statements)

References 34 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is important to note that in diabetes, proteins of glomerular matrix would be exposed to the elevated levels of reactive carbonyl compound for years before the appearance of the initial clinical signs of nephropathy. A long time needed for development of diabetic nephropathy, very slow turnover of matrix proteins, the fact that the concentration of circulating MGO correlates positively with duration of diabetes (8), and the presence of MGO-and 3-DG-derived arginine modifications in renal glomeruli of diabetic rats and in glomerular mesangial matrix of diabetic patients (23,25,69) support the notion that our proposed mechanism may be operable under diabetic conditions in vivo.…”

Section: Discussionsupporting

confidence: 77%

Mechanism of Perturbation of Integrin-Mediated Cell-Matrix Interactions by Reactive Carbonyl Compounds and Its Implication for Pathogenesis of Diabetic Nephropathy

et al. 2005

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 77%

Mechanism of Perturbation of Integrin-Mediated Cell-Matrix Interactions by Reactive Carbonyl Compounds and Its Implication for Pathogenesis of Diabetic Nephropathy

et al. 2005

View full text Add to dashboard Cite

“…Emerging evidence supports an important role for reactive ␣-dicarbonyls as intermediates in protein glycation and AGE formation, which in turn lead to diabetic complications (37)(38)(39)(40)(41). In the current study, we investigated the impact of postprandial glucose reduction with insulin lispro versus regular human insulin on the formation of ␣-dicarbonyls in patients with type 1 diabetes in which HbA 1c is not statistically different.…”

Section: Figure 2-mean ϯ Sd Integrated Postprandial Excursions Of Metmentioning

confidence: 89%

α-Dicarbonyls Increase in the Postprandial Period and Reflect the Degree of Hyperglycemia

Beisswenger

Howell

O’Dell³

et al. 2001

Diabetes Care

165

125

View full text Add to dashboard Cite

OBJECTIVE -Chronic hyperglycemia is known to increase tissue glycation and diabetic complications, but controversy exists regarding the independent role of increased postprandial glucose excursions. To address this question, we have studied the effect of postprandial glycemic excursions (PPGEs) on levels of methylglyoxal (MG) and 3-deoxyglucosone (3-DG), two highly reactive precursors of advanced glycation end products (AGEs).RESEARCH DESIGN AND METHODS -We performed 4-month crossover studies on 21 subjects with type 1 diabetes and compared the effect of premeal insulin lispro or regular insulin on PPGEs and MG/3-DG excursions. PPGE was determined after standard test meal (STMs) and by frequent postprandial glucose monitoring. HbA 1c and postprandial MG and D-lactate were measured by HPLC, whereas 3-DG was determined by gas chromatography/mass spectroscopy.RESULTS -Treatment with insulin lispro resulted in a highly significant reduction in PPGEs relative to the regular insulin-treated group (P ϭ 0.0005). However, HbA 1c levels were similar in the two groups, and no relationship was observed between HbA 1c and PPGE (P ϭ 0.93). Significant postprandial increases in MG, 3-DG, and D-lactate occurred after the STM. Excursions of MG and 3-DG were highly correlated with levels of PPGE (R ϭ 0.55, P ϭ 0.0002 and R ϭ 0.61, P ϭ 0.0004; respectively), whereas a significant inverse relationship was seen between PPGE and D-lactate excursions (R ϭ 0.40, P ϭ 0.01). Conversely, no correlation was observed between HbA1c and postprandial MG, 3-DG, or D-lactate levels.CONCLUSIONS -Increased production of MG and 3-DG occur with greater PPGE, whereas HbA1c does not reflect these differences. Reduced PPGE also leads to increased production of D-lactate, indicating a role for increased detoxification in reducing MG levels. The higher postprandial levels of MG and 3-DG observed with greater PPGE may provide a partial explanation for the adverse effects of glycemic lability and support the value of agents that reduce glucose excursions. Diabetes Care 24:726 -732, 2001

show abstract

“…The reaction of glyoxal or methylglyoxal (Paul et al, 1998, and references therein) or 3-deoxyglucosone (Niwa et al, 1997, and references therein) with the guanidino group of arginine can lead to formation of AGES called imidazolones (Figure 6). These are structurally related to, but are probably not precursors of, aminoimidazoline imine crosslinks.…”

Section: Imidazolonesmentioning

confidence: 99%

Protein Glycation, Diabetes, and Aging

Ulrich¹,

Cerami²

2001

Recent Progress in Hormone Research

731

541

View full text Add to dashboard Cite

Biologicalamines react with reducing sugars to form a complex family of rearranged and dehydrated covalent adducts that are often yellow-brown and/or fluorescent and include many crosslinked structures. Food chemists have long studied this process as a source of flavor, color, and texture changes in cooked, processed, and stored foods. During the 1970s and 198Os, it was realized that this process, called the Maillard reaction or advanced glycation, also occurs slowly in vivo. Advanced glycation endproducts (AGES) that form are implicated, causing the complications of diabetes and aging, primarily via adventitious and crosslinking of proteins. Long-lived proteins such as structural collagen and lens crystallins particularly are implicated as pathogenic targets of AGE processes, AGE formation in vascular wall collagen appears to be an especially deleterious event, causing crosslinking of collagen molecules to each other and to circulating proteins. This leads to plaque formation, basement membrane thickening, and loss of vascular elasticity. The chemistry of these later-stage, glycation-derrved crosslinks is still incompletely understood but, based on the hypothesis that AGE formation involves reactive carbonyl groups, the authors introduced the carbonyl reagent aminoguanidine hydrochloride as an inhibitor of AGE formation in vivo in the mid 1980s. Subsequent studies by many researchers have shown the effectiveness of aminoguanidine in slowing or preventing a wide range of complications of diabetes and aging in animals and, recently, in humans. Since, the authors have developed a new class of agents, exemplified by 4,5-dimethyl-3-phenacylthiazolium chloride (DPTC), which can chemically break already-formed AGE protein-protein crosslinks. These agents are based on a new theory of AGE crosslinking that postulates that a-dicarbonyl structures are present in AGE protein-protein crosslinks. In studies in aged animals, DPTC has been shown to be capable of reverting indices of vascular compliance to levels seen in younger animals. Human clinical trials are underway.

show abstract

Imidazolone, a novel advanced glycation end product, is present at high levels in kidneys of rats with streptozotocin‐induced diabetes

Cited by 56 publications

References 34 publications

Mechanism of Perturbation of Integrin-Mediated Cell-Matrix Interactions by Reactive Carbonyl Compounds and Its Implication for Pathogenesis of Diabetic Nephropathy

Mechanism of Perturbation of Integrin-Mediated Cell-Matrix Interactions by Reactive Carbonyl Compounds and Its Implication for Pathogenesis of Diabetic Nephropathy

α-Dicarbonyls Increase in the Postprandial Period and Reflect the Degree of Hyperglycemia

Protein Glycation, Diabetes, and Aging

Contact Info

Product

Resources

About