Age-dependent accumulation of advanced glycation endproducts is accelerated in combined hyperlipidemia and hyperglycemia, a process attenuated by L-arginine.

Abstract

In this study we have investigated the occurrence of "classical" Amadori rearrangement products of AGE-proteins in the vascular mesenteric bed and in the lens of Golden Syrian hamsters (12 weeks old) rendered simultaneous hyperlipidemics-diabetics (HD), or hyperlipidemics (H) for 24 weeks. For the next 4 weeks the hamsters in HD and H groups received by gavage a solution of 3 mM L-arginine, with the intent to look for the potential effects of L-arginine on the fluorescence of tissular AGE-proteins. Age-matched normal hamsters were used as controls (C). The AGE-products of proteins, and the AGE-collagen isolated from the mesenteric bed were quantitated by fluorescence spectroscopy at ex: 370 nm/em: 440 nm. The results showed that: (i) compared to the fluorescence levels of AGE-proteins detected at C goup, in HD group the fluorescence of AGE-proteins was found 2.78 and 7.41 fold increased in the vascular mesenteric bed and lens, respectively; (ii) in H group the fluorescence of AGE-proteins was 2.36 fold augumented in the vascular mesenteric bed, and 5.43 fold in the lens (versus the C goup); (iii) the aging occurring during the 24 weeks of the experiment induced a small increase in AGE-proteins fluorescence in both mesentery (1.76 fold) and lens (3.83 fold), compared to the levels measured in C group at the inception of the study (12 weeks old hamsters); (iv) the fluorescence of AGE-proteins in the vascular mesenteric bed and in the lens of hamsters in HD and H groups correlated with the increase in circulating plasma glucose and cholesterol concentrations throughout the experiment; (v) L-arginine dietary supplementation in HD and H groups, diminished the AGE-collagen fluorescence in the mesentery to ∼ 35% and ∼ 17%, respectively; in the lens the fluorescence of AGE-proteins was reduced to 65-70% of the levels found in HD and H groups (at 24 weeks). This study showed for the first time that simultaneous hyperlipidemia-hyperglycemia induced an enhanced accumulation of fluorescent AGE-proteins in the mesentery and lens (comparatively to the effect of hyperlipidemia and of chronological aging monitored during the experiment), and that in vivo L-arginine administration decreased the fluorescence of tissular AGE-proteins (AGE-collagen included). The latter observation may bring another area of potential intervention in the adjunct efforts to find out inhibitors of AGE formation, and thus to reduce the increased levels of AGE-proteins accumulated in tissues when diabetes is additionally complicated with atherosclerosis.