d -Ribose as a Contributor to Glycated Haemoglobin

Abstract

Glycated haemoglobin (HbA1c) is the most important marker of hyperglycaemia in diabetes mellitus. We show that d-ribose reacts with haemoglobin, thus yielding HbA1c. Using mass spectrometry, we detected glycation of haemoglobin with d-ribose produces 10 carboxylmethyllysines (CMLs). The first-order rate constant of fructosamine formation for d-ribose was approximately 60 times higher than that for d-glucose at the initial stage. Zucker Diabetic Fatty (ZDF) rat, a common model for type 2 diabetes mellitus (T2DM), had high levels of d-ribose and HbA1c, accompanied by a decrease of transketolase (TK) in the liver. The administration of benfotiamine, an activator of TK, significantly decreased d-ribose followed by a decline in HbA1c. In clinical investigation, T2DM patients with high HbA1c had a high level of urine d-ribose, though the level of their urine d-glucose was low. That is, d-ribose contributes to HbA1c, which prompts future studies to further explore whether d-ribose plays a role in the pathophysiological mechanism of T2DM.

CompromisedDNArepair is responsible for diabetes‐associated fibrosis

“…Thus, to simulate the pathological consequences of high blood sugar spikes in cultured cells in short time, we used high sugar concentrations. Moreover, considering the clinical scores of poorly managed diabetes in juvenile or a postprandial slot, the glucose levels in diabetics can be around 12-20 mM and the levels of other reducing sugars such as fructose or ribose can be around (0.6-1.9 mM) or (~100 lM), respectively (Gross & Zollner, 1991;Sidhu et al, 2001;Clark et al, 2014;Laughlin, 2014;Chen et al, 2017;Wang et al, 2018). Thus, to simulate the pathologically relevant hyperglycemic conditions, the DNA repair studies were repeated with cells maintained under 17 mM glucose (for 5, 10, or 15 days).…”

Formaldehyde produced from d-ribose under neutral and alkaline conditions

“…Accumulation of a pathological concentration of endogenous formaldehyde (15 μM) induced chronic damage to N2a cells [24,51], especially the impairment of neuronal processes and neurites, which may result from Tau hyperphosphorylation [51]. As described previously [52], the elevation of brain formaldehyde levels resulted from the administration of d -ribose may lead to cognitive impairment. According to the current results, administration of d -ribose elevated the brain formaldehyde level to greater than 15 μM/g.…”

Connecting Alzheimer’s Disease With Diabetes Mellitus Through Amyloidogenic Evolvability

“…Notably, administration of D-ribose leads to an increase of visceral triglycerides in mice (Chen et al, 2019b); and since high levels of D-ribose (Su et al, 2013;Chen et al, 2019a) and high HbA1c (Chen et al, 2017) are associated with diabetes, this raises a possibility that D-ribose could be utilized as a biomarker to assess the therapeutic efficiency.…”