The Abnormally High Level of Uric D-Ribose for Type-2 Diabetics

Su, Tao; Liang, Xuefang; He, Yingge; Yan, Wei; Song, Yi-xiang; Li, Weiwei; Wang, Xuemei; He, Rong

doi:10.3724/sp.j.1206.2013.00341

Cited by 21 publications

(34 citation statements)

References 7 publications

(11 reference statements)

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“…Biochemically, the glycation reaction initiates with the formation of a reversible Schiff base between a carbohydrate, typically glucose or ribose [12], and a protein amino group (e.g., a lysine side-chain). The unstable Schiff base becomes a stable keto amine intermediate, usually referred to as Amadori product.…”

Section: Introductionmentioning

confidence: 99%

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue

et al. 2017

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Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45 nm to 1.5 nm) and a decrease in the D-period length (from 67.5 nm to 67.1 nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue.

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Section: Introductionmentioning

confidence: 99%

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue

et al. 2017

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“…The role of ribose in in vivo and in vitro glycation processes has recently attracted a lot of attention after abnormally high levels of D-ribose were detected in the urine of type 2 diabetic patients [ 47 ] suggesting that these patients not only suffer from disorders in glucose metabolism but also from ribose metabolism disorders. A few earlier in vitro studies established that ribosylation led to protein aggregation [ 48 ], significant alteration of the collagen structure [ 49 ] as well as the reduced proliferation, increased necrosis and apoptosis of cultured pancreatic islet beta-cells exposed to the ribosylated fetal calf serum [ 50 ].…”

Section: Introductionmentioning

confidence: 99%

Glycation of Human Cortical and Cancellous Bone Captures Differences in the Formation of Maillard Reaction Products between Glucose and Ribose

2015

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To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs) at the levels that corresponded to approx. 25–30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation) or ribose (ribosylation). Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN) in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women). More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples). Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar supplementation in food and drinks.

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“…Hammes and collaborators used benfotiamine to block three major pathways of hyperglycemia damage and prevent experimental diabetic retinopathy (Hammes et al ., 2003 ). Su and colleagues found that D-ribose is significantly increased in the urine of patients with type 2 diabetes mellitus, accompanied with high levels of D-glucose (Su et al ., 2013 ), suggesting that T2DM is not only related with a dysfunction in D-glucose metabolism, but also in D-ribose metabolism (Su & He, 2014 ). On the other hand, D-ribose is an efficient glycator (Chen et al ., 2009 , 2010 ; Wei et al ., 2009 ) and is much more active in protein glycation than D-glucose under identical conditions.…”

Section: Introductionmentioning

confidence: 99%

Ribosylation triggering Alzheimer's disease‐like Tau hyperphosphorylation via activation of CaMKII

et al. 2015

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Type 2 diabetes mellitus (T2DM) is regarded as one of the serious risk factors for age-related cognitive impairment; however, a causal link between these two diseases has so far not been established. It was recently discovered that, apart from high D-glucose levels, T2DM patients also display abnormally high concentrations of uric D-ribose. Here, we show for the first time that the administration of D-ribose, the most active glycator among monosaccharides, produces high levels of advanced glycation end products (AGEs) and, importantly, triggers hyperphosphorylation of Tau in the brain of C57BL/6 mouse and neuroblastoma N2a cells. However, the administration of D-glucose showed no significant changes in Tau phosphorylation under the same experimental conditions. Crucially, suppression of AGE formation using an AGEs inhibitor (aminoguanidine) effectively prevents hyperphosphorylation of Tau protein. Further study shows AGEs resulted from ribosylation activate calcium-/calmodulin-dependent protein kinase type II (CaMKII), a key kinase responsible for Tau hyperphosphorylation. These data suggest that there is indeed a mechanistic link between ribosylation and Tau hyperphosphorylation. Targeting ribosylation by inhibiting AGE formation may be a promising therapeutic strategy to prevent Alzheimer’s disease-like Tau hyperphosphorylation and diabetic encephalopathies.

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The Abnormally High Level of Uric D-Ribose for Type-2 Diabetics

Cited by 21 publications

References 7 publications

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue

Glycation of Human Cortical and Cancellous Bone Captures Differences in the Formation of Maillard Reaction Products between Glucose and Ribose

Ribosylation triggering Alzheimer's disease‐like Tau hyperphosphorylation via activation of CaMKII

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