d-Lysine reduces the non-enzymatic glycation of proteins in experimental diabetes mellitus in rats

Sensi, M.; Rossi, Maria Grazia; Celi, Francesco S.; Cristina, A.; Rosati, Clelia; Perrett, David; Andreani, D; Mario, U. Di

doi:10.1007/bf00400352

Cited by 29 publications

(22 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These include acetylsalicylic acid [12, 13, 14, 15, 16, 17, 18, 19], L -lysine [14, 20], D -lysine [21, 22, 23], L -arginine [24], vitamin C [20, 25, 26, 27, 28, 29], vitamin E [30], bendazac [31], and aminoguanidine [4, 5, 6, 7, 8, 9, 10, 32, 33]. Other novel therapeutic agents have been shown to improve albuminuria and mesangial expansion in diabetic mice [34, 35]and rats [36], with type 2 diabetes melllitus.…”

Section: Introductionmentioning

confidence: 99%

<i>L</i>-Lysine Reduces Nonenzymatic Glycation of Glomerular Basement Membrane Collagen and Albuminuria in Diabetic Rats

Jyothirmayi¹,

Modak²,

Reddi³

2001

Nephron

View full text Add to dashboard Cite

In this study, we examined the hypothesis whether exogenous administration of L-lysine in drinking water would reduce nonenzymatic glycation of glomerular basement membrane (GBM) collagen and thus albuminuria in streptozotocin-diabetic rats. The rationale is that the administered lysine would combine with the circulating glucose and make it unavailable to react with Ε-amino groups of lysine of various proteins in these diabetic rats. Lysine (0.1%) was given to diabetic rats 7 days (early treatment) or 90 days (late treatment) after induction of hyperglycemia. The treatment was continued for 60 days. Diabetic rats had significantly higher glucose, glycosylated HbA₁, kidney weight, nonenzymatic glycation of GBM collagen, albuminuria, and systolic blood pressure than normal rats. Early treatment with lysine prevented the rise in glycosylated HbA₁ (normal 6.98 ± 0.71% vs. diabetic – early treatment – 7.78 ± 1.50%; p = NS), reduced glycosylation of GBM collagen by 86%, and significantly improved albuminuria. There was no significant effect on plasma glucose and systolic blood pressure. However, late treatment reduced the glycosylation of GBM collagen by 46% with a significant improvement in albuminuria. Plasma creatinine levels were not different between normal and untreated diabetic or lysine-treated diabetic rats; however, the creatinine clearance was significantly higher in all groups of diabetic rats (normal 0.45 ± 0.09 vs. diabetic 2.02 ± 0.39 ml/min; p < 0.001). The data suggest that early rather than late treatment is more beneficial in reducing nonenzymatic glycation of collagen, although both treatments significantly reduced albuminuria. There was no nephrotoxicity as assessed by plasma creatinine levels or creatinine clearances. These beneficial effects occurred independent of changes either in blood pressure or plasma insulin concentration.

show abstract

Section: Introductionmentioning

confidence: 99%

<i>L</i>-Lysine Reduces Nonenzymatic Glycation of Glomerular Basement Membrane Collagen and Albuminuria in Diabetic Rats

Jyothirmayi¹,

Modak²,

Reddi³

2001

Nephron

View full text Add to dashboard Cite

show abstract

“…This result is consistent with the previous studies. D-Lysine could reduce the nonenzymatic glycation of proteins in experimental diabetes mellitus in rats and oral lysine treatment could therefore enhance the insulin receptor tyrosine kinase activity in patients with diabetes and decrease their blood sugar (Sensi et al 1993;Mogensen, Vittinghus, and Solling 1979). In our study, the fact that plasma lysine concentrations in diabetes patients are significantly higher than those in controls demonstrates that diabetes plasma lysine accumulation occurs and the lysine-regulated downstream of pathway changes in diabetes.…”

Section: Amino Acid Biomarkers For Type 2 Diabetes Mellitus 2821mentioning

confidence: 47%

Determination of Plasma Amino Acid Biomarkers by High Performance Liquid Chromatography for Diagnosis of Type 2 Diabetes Mellitus

et al. 2013

View full text Add to dashboard Cite

The use of the fasting plasma glucose and 2-h plasma glucose tolerance tests leads to under-diagnosis of type 2 diabetes mellitus. To explore the contribution of metabolites for diagnosis for type 2 diabetes, plasma targeted metabolites (including free amino acids, lipids, and two hepatic aminotransferases) of 95 subjects were determined by high performance liquid chromatography and routine clinical methods. Receiver operating characteristic curve analysis was employed to evaluate potential diagnosis models. Based on the processing of orthogonal partial least squares-discriminant analysis, five amino acids (lysine, aspartate acid, threonine, methionine, and alanine) and two lipids (low density lipoprotein-cholesterol and high density lipoprotein-cholesterol) were discovered as potential biomarkers of type 2 diabetes. The area under the receiver operating characteristic curve built by the combination of these biomarkers and fasting plasma glucose was 0.994, which is significantly higher than that of the latter alone (0.907). These findings indicate that simultaneous measurement of specific metabolites with fasting plasma glucose from a single blood test for screening type 2 diabetes might be a more sensitive and specific strategy and provide additional insight regarding disease pathophysiologic mechanisms.

show abstract

“…AGEs induce more significant protein modification than early glycation products [9][10][11]. It was, therefore, of interest that in the current investigation, the amino acid D-lysine, a competitive inhibitor of early nonenzymatic glycosylation [12,13], produced a more profound reduction in RVEC endocytosis than aminoguanidine. However, both can inhibit the distal AGE product formation and both may interact with the same AGE intermediate, following the formation of an Amadori product [14].…”

Section: Discussionmentioning

confidence: 96%

Increased endocytosis in retinal vascular endothelial cells grown in high glucose medium is modulated by inhibitors of nonenzymatic glycosylation

Stitt¹,

Chakravarthy²,

Archer³

et al. 1995

Diabetologia

View full text Add to dashboard Cite

SummaryWe sought to determine if hyperglycaemia is responsible for increased retinal vascular endothelial-cell (RVEC) endocytosis in diabetes and to assess the role of nonenzymatic glycosylation in mediation of this novel endothelial-cell pathology. RVECs were propagated in media containing either 5 or 25 mmol/1 glucose for up to 10 days after which they were exposed to the protein tracer horseradish peroxidase for 30 min. The level of RVEC endocytosis was quantified in intact cell monolayers by electron microscopic stereology, and in cell lysates by a simple spectrophotometric method. The effect of the nonenzymatic glycosylation inhibitors, aminoguanidine and D-lysine, on high-glucose medium induced changes in RVEC endocytosis was tested by inclusion of these agents in the culture medium. RVECs exposed to 25 mmol/1 glucose showed a stepwise increase in endocytosis of horseradish peroxidase culminating in a two-to threefold increase after 10 days. Endocytosis returned to normal levels after a further 10 days in 5 mmol/1 glucose medium. The increase in RVEC endocytosis was markedly reduced, but not completely normalised, by aminoguanidine and D-lysine. Exposure of cultured RVECs to 25 mmol/1 glucose causes an increase in endocytosis of similar magnitude to that experienced by RVEC in early diabetes, and implicates hyperglycaemia in the latter situation. A significant component of the increase in RVEC endocytosis appears to be mediated by nonenzymatic glycosylation. [Diabetologia (1995[Diabetologia ( ) 38: 1271[Diabetologia ( -1275 Key words Endocytosis, high glucose, nonenzymatic glycosylation, endothelium.A recent study has shown a more than sixfold increase in endocytosis of horseradish peroxidase (HRP) by the endothelium of the retinal microvessels in 6-week diabetic rats, without an associated increase in capillary permeability [1]. This finding is in accord with many previous studies which have demonstrated an increased clearance of intravascular protein tracers by the retina of streptozotocin diabetic rats after similar durations of diabetes [2,3]. The

show abstract

d-Lysine reduces the non-enzymatic glycation of proteins in experimental diabetes mellitus in rats

Cited by 29 publications

References 24 publications

<i>L</i>-Lysine Reduces Nonenzymatic Glycation of Glomerular Basement Membrane Collagen and Albuminuria in Diabetic Rats

<i>L</i>-Lysine Reduces Nonenzymatic Glycation of Glomerular Basement Membrane Collagen and Albuminuria in Diabetic Rats

Determination of Plasma Amino Acid Biomarkers by High Performance Liquid Chromatography for Diagnosis of Type 2 Diabetes Mellitus

Increased endocytosis in retinal vascular endothelial cells grown in high glucose medium is modulated by inhibitors of nonenzymatic glycosylation

Contact Info

Product

Resources

About