Abstract
Advanced glycation end products (AGEs) promote the development of diabetic complications through activation of their receptor (RAGE). Isoforms of soluble RAGE (sRAGE) sequester AGEs and protect against RAGE-mediated diabetic complications. We investigated the effect of an overnight fast on circulating metabolic substrates, hormones, AGEs, and sRAGE isoforms in 26 individuals with type 1 diabetes (T1DM). Blood was collected from 26 young (18–30 years) T1DM patients on insulin pumps before and after an overnight fast. Circulating AGEs were measured via LC-MS/MS and sRAGE isoforms were analyzed via ELISA. Glucose, insulin, glucagon, and eGFRcystatin-c decreased while cortisol increased following the overnight fast (p < 0.05). AGEs (CML, CEL, 3DG-H, MG-H1, and G-H1) decreased (21–58%, p < 0.0001) while total sRAGE, cleaved RAGE (cRAGE), and endogenous secretory RAGE (esRAGE) increased (22–24%, p < 0.0001) following the overnight fast. The changes in sRAGE isoforms were inversely related to MG-H1 (rho = −0.493 to −0.589, p < 0.05) and the change in esRAGE was inversely related to the change in G-H1 (rho = −0.474, p < 0.05). Multiple regression analyses revealed a 1 pg/mL increase in total sRAGE, cRAGE, or esRAGE independently predicted a 0.42–0.52 nmol/L decrease in MG-H1. Short-term energy restriction via an overnight fast resulted in increased sRAGE isoforms and may be protective against AGE accumulation.
Highlights
Advanced glycation end products (AGEs) are a heterogeneous group of glycotoxins formed exogenously via the Maillard Reaction [1] and endogenously via a number of mechanisms
We explored the ability of soluble RAGE (sRAGE)
We examined the relationship between the change in sRAGE isoforms and MG-H1 while controlling for the change in eGFRCystatin-C by utilizing partial correlations
Summary
Advanced glycation end products (AGEs) are a heterogeneous group of glycotoxins formed exogenously via the Maillard Reaction [1] and endogenously via a number of mechanisms. The endogenous formation of AGEs is slow and the clearance rate is adequate to prevent their accumulation [2]. The chronic oxidative stress and hyperglycemia conditions that characterize type 1 (T1DM) and Type 2 diabetes mellitus (T2DM), accelerate AGE formation leading to the accumulation of AGE-modified proteins in tissues and in circulation [3,4,5]. AGE-modified proteins in tissues are subsequently degraded releasing AGE-free adducts into the circulation. Nutrients 2019, 11, 386 reactive α-dicarbonyls which include, methylglyoxal (MG), glyoxal (GO) and 3-deoxyglucosone (3DG) [5,6]. These α-dicarbonyls react primarily with arginine residues to form hydroimidazolone
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