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Glyoxylate, a new marker metabolite of type 2 diabetes.

Nikiforova VJ, Giesbertz P, Wiemer J, Bethan B, Looser R, Liebenberg V, Ruiz Noppinger P, Daniel H, Rein D - J Diabetes Res (2014)

Bottom Line: Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs).Reactive aldehydes derived from sugars play an important role in the generation of AGEs.Elevated glyoxylate levels impact on newly identified mechanisms linking hyperglycemia and AGE production with diabetes-associated complications such as diabetic nephropathy.

View Article: PubMed Central - PubMed

Affiliation: Metanomics Health GmbH, 10589 Berlin, Germany ; Timiryazev Institute of Plant Physiology, Russian Academy of Sciences, Moscow 127276, Russia.

ABSTRACT
Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs). Reactive aldehydes derived from sugars play an important role in the generation of AGEs. Using metabolite profiling to characterize human plasma from diabetic versus nondiabetic subjects we observed in a recent study that the reactive aldehyde glyoxylate was increased before high levels of plasma glucose, typical for a diabetic condition, could be measured. Following this observation, we explored the relevance of increased glyoxylate in diabetic subjects and in diabetic C57BLKS/J-Lepr (db/db (-/-)) mice in the pathophysiology of diabetes. A retrospective study using samples of long-term blood donors revealed that glyoxylate levels unlike glucose levels became significantly elevated up to 3 years prior to diabetes diagnosis (difference to control P = 0.034). Elevated glyoxylate levels impact on newly identified mechanisms linking hyperglycemia and AGE production with diabetes-associated complications such as diabetic nephropathy. Glyoxylate in its metabolic network may serve as an early marker in diabetes diagnosis with predictive qualities for associated complications and as potential to guide the development of new antidiabetic therapies.

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Related in: MedlinePlus

Correlation matrix with glyoxylate and precursors/products of glyoxylate metabolism. Kendall's tau correlations between metabolite levels of glyoxylate, glycine and 4-hydroxyproline in liver (L), muscle (M), and plasma (P) and of glycolate in plasma are visualized. Blue shades represent positive correlations and red shades represent negative correlations. The more the circle is filled, the higher the absolute correlation is.
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fig1: Correlation matrix with glyoxylate and precursors/products of glyoxylate metabolism. Kendall's tau correlations between metabolite levels of glyoxylate, glycine and 4-hydroxyproline in liver (L), muscle (M), and plasma (P) and of glycolate in plasma are visualized. Blue shades represent positive correlations and red shades represent negative correlations. The more the circle is filled, the higher the absolute correlation is.

Mentions: The C57BLKS/J-Leprdb/db−/−Diabetes Mouse Model. C57BLKS/J-Leprdb/db−/− (db/db−/−) mice display a phenotype that resembles in many aspects that of humans with metabolic syndrome or diabetes characterized by hyperphagia, obesity, and hyperglycemia. Metabolite profiling revealed a 6-fold increase in plasma glyoxylate levels in db/db−/− mice as compared to wild-type animals (Table 2). Tissue metabolite profiling did not reveal a difference in liver glyoxylate levels but showed a small, yet significant, decrease in muscle glyoxylate levels (P = 0.025). Putative precursors or products of glyoxylate production and utilization with strong concentration changes were identified. Glycine was strongly decreased in liver and muscle tissue, but it was not significantly changed in plasma. 4-Hydroxyproline was strongly decreased in liver, muscle, and plasma. Correlation analysis, however, did not reveal robust associations between plasma or tissue levels of glyoxylate, glycine, or 4-hydroxyproline (see Figure 1). Also, no strong correlation was found between glyoxylate and glycolate in plasma. Significant correlations were only observed for 4-hydroxyproline between plasma and tissues.


Glyoxylate, a new marker metabolite of type 2 diabetes.

Nikiforova VJ, Giesbertz P, Wiemer J, Bethan B, Looser R, Liebenberg V, Ruiz Noppinger P, Daniel H, Rein D - J Diabetes Res (2014)

Correlation matrix with glyoxylate and precursors/products of glyoxylate metabolism. Kendall's tau correlations between metabolite levels of glyoxylate, glycine and 4-hydroxyproline in liver (L), muscle (M), and plasma (P) and of glycolate in plasma are visualized. Blue shades represent positive correlations and red shades represent negative correlations. The more the circle is filled, the higher the absolute correlation is.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4265698&req=5

fig1: Correlation matrix with glyoxylate and precursors/products of glyoxylate metabolism. Kendall's tau correlations between metabolite levels of glyoxylate, glycine and 4-hydroxyproline in liver (L), muscle (M), and plasma (P) and of glycolate in plasma are visualized. Blue shades represent positive correlations and red shades represent negative correlations. The more the circle is filled, the higher the absolute correlation is.
Mentions: The C57BLKS/J-Leprdb/db−/−Diabetes Mouse Model. C57BLKS/J-Leprdb/db−/− (db/db−/−) mice display a phenotype that resembles in many aspects that of humans with metabolic syndrome or diabetes characterized by hyperphagia, obesity, and hyperglycemia. Metabolite profiling revealed a 6-fold increase in plasma glyoxylate levels in db/db−/− mice as compared to wild-type animals (Table 2). Tissue metabolite profiling did not reveal a difference in liver glyoxylate levels but showed a small, yet significant, decrease in muscle glyoxylate levels (P = 0.025). Putative precursors or products of glyoxylate production and utilization with strong concentration changes were identified. Glycine was strongly decreased in liver and muscle tissue, but it was not significantly changed in plasma. 4-Hydroxyproline was strongly decreased in liver, muscle, and plasma. Correlation analysis, however, did not reveal robust associations between plasma or tissue levels of glyoxylate, glycine, or 4-hydroxyproline (see Figure 1). Also, no strong correlation was found between glyoxylate and glycolate in plasma. Significant correlations were only observed for 4-hydroxyproline between plasma and tissues.

Bottom Line: Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs).Reactive aldehydes derived from sugars play an important role in the generation of AGEs.Elevated glyoxylate levels impact on newly identified mechanisms linking hyperglycemia and AGE production with diabetes-associated complications such as diabetic nephropathy.

View Article: PubMed Central - PubMed

Affiliation: Metanomics Health GmbH, 10589 Berlin, Germany ; Timiryazev Institute of Plant Physiology, Russian Academy of Sciences, Moscow 127276, Russia.

ABSTRACT
Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs). Reactive aldehydes derived from sugars play an important role in the generation of AGEs. Using metabolite profiling to characterize human plasma from diabetic versus nondiabetic subjects we observed in a recent study that the reactive aldehyde glyoxylate was increased before high levels of plasma glucose, typical for a diabetic condition, could be measured. Following this observation, we explored the relevance of increased glyoxylate in diabetic subjects and in diabetic C57BLKS/J-Lepr (db/db (-/-)) mice in the pathophysiology of diabetes. A retrospective study using samples of long-term blood donors revealed that glyoxylate levels unlike glucose levels became significantly elevated up to 3 years prior to diabetes diagnosis (difference to control P = 0.034). Elevated glyoxylate levels impact on newly identified mechanisms linking hyperglycemia and AGE production with diabetes-associated complications such as diabetic nephropathy. Glyoxylate in its metabolic network may serve as an early marker in diabetes diagnosis with predictive qualities for associated complications and as potential to guide the development of new antidiabetic therapies.

Show MeSH
Related in: MedlinePlus