Glucosepane: a poorly understood advanced glycation end product of growing importance for diabetes and its complications

Monnier, Vincent M.; Sun, Wanjie; Sell, David R.; Fan, Xingjun; Nemet, Ina; Genuth, Saul

doi:10.1515/cclm-2013-0174

Cited by 64 publications

(39 citation statements)

References 37 publications

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“…AGE-induced alterations in the vasculature may contribute to greater arterial stiffness [11,16]. AGEs such as CML and glucosepane can alter the extracellular matrix by cross-linking type-IV collagen and inhibiting the association of these molecules into a normal complex network-like structure [27,28] and cross-linking with laminin to inhibit polymer self-assembly [29,30]. Other biological mechanisms by which AGEs could contribute to alterations in the vasculature include potentiation of endothelial dysfunction through impairment of nitric oxide production [31], increased oxidation of low-density lipoprotein [32], and increased production of reactive oxygen species [33].…”

Section: Discussionmentioning

confidence: 99%

Serum carboxymethyl-lysine, an advanced glycation end product, is associated with arterial stiffness in older adults

Semba

Sun

Schwartz

et al. 2015

Journal of Hypertension

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Objective To examine the relationship of serum carboxymethyl-lysine (CML), an advanced glycation end product (AGE), with pulse pressure (PP), aortic pulse wave velocity (aPWV), and hypertension in older adults. Background AGEs are bioactive molecules that accumulate in tissues with aging and can both cross-link collagen and induce inflammation in model systems. The relationship of AGEs with arterial stiffness and hypertension has not been well characterized in community-dwelling older adults. Methods We measured serum CML and blood pressure in 3044 adults, aged 70–79 y, who participated in the Health, Aging and Body Composition Study, a population-based study of aging in Pittsburgh, Pennsylvania, and Memphis, Tennessee. aPWV was measured in 2468 participants. Results Participants in the highest tertile of serum CML had higher PP (highest tertile: beta = 2.85, SE = 0.82, P = 0.0005; middle tertile: beta = 0.60, SE = 0.80, P = 0.45), and higher aPWV (highest tertile: beta = 51.4, SE = 20.1, P = 0.01; middle tertile: beta = 3.2, SE = 19.8, P = 0.87) compared with those in the lowest tertile in multivariable linear regression models adjusting for age, sex, race, education, BMI, smoking, alcohol use, total cholesterol, HDL cholesterol, diabetes, cardiovascular disease, and chronic kidney disease. Participants in the highest and middle tertiles of serum CML had higher odds of hypertension (Odds Ratio [O.R.] 1.32, 95% Confidence Interval [C.I.] 1.06, 1.60, P = 0.005; O.R. 1.27, 95% C.I. 1.05, 1.53, P = 0.01, respectively) compared with the lowest tertile in a multivariable logistic regression model adjusting for the same covariates. Conclusions Elevated serum CML was associated with arterial stiffness, as reflected by higher PP and aPWV, in older, community-dwelling adults.

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Section: Discussionmentioning

confidence: 99%

Serum carboxymethyl-lysine, an advanced glycation end product, is associated with arterial stiffness in older adults

Semba

Sun

Schwartz

et al. 2015

Journal of Hypertension

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“…Mechanistically, AGE accumulation in the bone matrix is thought to impede collagen fibril deformation, thus reducing energy dissipation and subsequently the fracture resistance of bone [16]. Other major AGE crosslinks such as glucosepane are not yet readily measurable in bone [17]. Nonetheless, a diabetic increase in overall bone PE has been directly observed in one study to date [18].…”

Section: Introductionmentioning

confidence: 99%

Changes in the Fracture Resistance of Bone with the Progression of Type 2 Diabetes in the ZDSD Rat

et al. 2016

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Individuals with type 2 diabetes (T2D) have a higher fracture risk compared to non-diabetics, even though their areal bone mineral density is normal to high. Identifying the mechanisms whereby diabetes lower fracture resistance requires well-characterized rodent models of diabetic bone disease. Toward that end, we hypothesized that the bone toughness, more so than bone strength, decreases with the duration of diabetes in ZDSD rats. Bones were harvested from male CD(SD) control rats and male ZDSD rats at 16-wks (before the onset of hyperglycemia), at 22-wks (5–6 wks of hyperglycemia), and at 29-wks (12–13 wks of hyperglycemia). There were at least 12 rats per strain per age group. At 16-wks, there was no difference in either body weight or glucose levels between the 2 rat groups. Within 2 weeks of switching all rats to a diet with 48% of kcal from fat, only the ZDSD rats developed hyperglycemia (>250 mg/dl). They also began to lose body weight at 21-wks. CD(SD) rats remained normoglycemic (<110 mg/dl) on the high fat diet and became obese (>600 g). From micro-computed tomography (µCT) analysis of a lumbar vertebra and distal femur, trabecular bone volume did not vary with age among the non-diabetic rats but was lower at 29-wks than at 16-wks or at 22-wks for the diabetic rats. Consistent with that finding, µCT-derived intra-cortical porosity (femur diaphysis) was higher for ZDSD following ~12 wks of hyperglycemia than for age-matched CD(SD) rats. Despite an age-related increase in mineralization in both rat strains (µCT and Raman spectroscopy), material strength of cortical bone (from three-point bending testing) increased with age only in the non-diabetic CD(SD) rats. Moreover, two other material properties, toughness (radius) and fracture toughness (femur), significantly decreased with the duration of T2D in ZDSD rats. This was accompanied by the increase in the levels of the pentosidine (femur). However, pentosidine was not significantly higher in diabetic than in non-diabetic bone at any time point. The ZDSD rat, which has normal leptin signaling and becomes diabetic after skeletal maturity, provides a pre-clinical model of diabetic bone disease, but a decrease in body weight during prolonged diabetes and certain strain-related differences before the onset of hyperglycemia should be taken into consideration when interpreting diabetes-related differences.

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“…For example glucose pane is the most important cross-link products formed with ECM, known in human skin [48], and the glycated-myosin mainly affects myosin velocity and directionality [49]. Furthermore, AGE accumulation in collagen leads to changes in the biochemical and structural property of the components of the basement membrane affecting for example its elasticity, ionic charge, and thickness [50].…”

Section: Citation: Abate G Delbarba a Marziano M Memo M Uberti D mentioning

confidence: 99%

Advanced Glycation End Products (Ages) in Food: Focusing on Mediterranean Pasta

Abate¹,

Delbarba²,

Marziano³

et al. 2015

J Nutr Food Sci

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Advanced glycation end products, also known as glycotoxins, are a diverse group of highly oxidant compounds with pathogenic significance in aged-chronic disease, including diabetes, cardiovascular disease and neurodegenerative disease. They are produced physiologically in the body when reducing sugar binds to a free amino acid group of macromolecules. Thus conditions such as hyperglycemia and/or oxidative stress can favor AGE product formation, contributing to ageing processes and the exacerbation of pathological states. Beside endogenous AGEs, dietary AGE intake contributes significantly to the body AGE pool. It assumes that if dietary AGE intake gets lower, any chronic disease, such as diabetes and cardiovascular disease can be ameliorated, and even cured. For this reason, recently great attention has been made on the identification and quantification of AGE products in the consumed foods. Here we reviewed some knowledge, found in literature, concerning the formation of AGEs in food, their gastrointestinal absorption, and their toxic effects. In addition original data on AGE content in the Mediterranean pasta was discussed in relation to their production processes and cooking time.

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Glucosepane: a poorly understood advanced glycation end product of growing importance for diabetes and its complications

Cited by 64 publications

References 37 publications

Serum carboxymethyl-lysine, an advanced glycation end product, is associated with arterial stiffness in older adults

Serum carboxymethyl-lysine, an advanced glycation end product, is associated with arterial stiffness in older adults

Changes in the Fracture Resistance of Bone with the Progression of Type 2 Diabetes in the ZDSD Rat

Advanced Glycation End Products (Ages) in Food: Focusing on Mediterranean Pasta

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