Abstract
It has been demonstrated in vivo that lipid glycation products such as Amadori-glycated phosphatidylethanolamine (Amadori-PE) accumulate in the plasma of diabetic humans and animals, but how lipid glycation products are formed under hyperglycemic conditions are not clear. We sought to clarify the occurrence of lipid glycation and its relationships with lipid peroxidation and protein glycation during the development of hyperglycemia using the streptozotocin (STZ)-induced diabetic rat model. A significant increase in Amadori-PE was observed in STZ rats 7 days after STZ treatment, and Amadori-PE (especially 18:0–20:4 Amadori-PE) was found at high levels in the blood and in organs that are strongly affected by diabetes, such as the kidney. Significant changes in Amadori-PE appeared to occur prior to changes in levels of oxidized lipids, which increased after 21–28 days. In addition, accumulation of Nε-(carboxymethyl)lysine (CML), a protein glycation product, proceeded somewhat more slowly and moderately than that of Amadori-PE, suggesting that Amadori-PE and CML are early and advanced glycation products, respectively. Our results suggest that Amadori-PE may be a useful predictive marker for hyperglycemia, particularly in the early stages of diabetes. Similar speculations have been made from previous human studies, but this study provides a direct evidence to support the speculations in rat study.
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Abbreviations
- 1,5-AG:
-
1,5-Anhydroglucitol
- ALT:
-
Alanine aminotransferase
- Amadori-PE:
-
Amadori-glycated phosphatidylethanolamine
- AST:
-
Aspartate aminotransferase
- CL:
-
Chemiluminescence
- CML:
-
Nε-(carboxymethyl)lysine
- HbA1c :
-
Hemoglobin A1c
- LC:
-
Liquid chromatography
- MRM:
-
Multiple reaction monitoring
- MS/MS:
-
Tandem mass spectrometry
- NFPA:
-
Nonafluoropentanoic acid
- NLS:
-
Neutral loss scanning
- PCOOH:
-
Phosphatidylcholine hydroperoxide
- PE:
-
Phosphatidylethanolamine
- PL:
-
Phospholipid
- RBC:
-
Red blood cells
- STZ:
-
Streptozotocin
- TBARS:
-
Thiobarbituric acid reactive substances
- T-cho:
-
Total cholesterol
- TAG:
-
Triacylglycerol
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Acknowledgments
A part of this study was supported by KAKENHI (S) (20228002, to T. M.) of JSPS, Japan.
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11745_2011_3588_MOESM1_ESM.pdf
Fig. S1 Time course of changes in total PE glycation rate (mol% of PE) in (A) plasma, (B) RBC, (C) liver, (D) kidney, (E) pancreas, (F) cerebrum, and (G) cerebellum. Values are means ± SD (n=6; *P < 0.05 and **P < 0.01). White circles represent control rats, and black circles represent STZ rats. (PDF 44.4 kb)
11745_2011_3588_MOESM2_ESM.pdf
Fig. S2 Glycation rates of Amadori-PE molecular species (mol% of PE) 28 days after STZ injection. (A) plasma, (B) RBC, (C) liver, (D) kidney, (E) pancreas, (F) cerebrum, and (G) cerebellum. Values are means ± SD (n = 6; *P < 0.05 and **P < 0.01). White bars represent control rats, and black bars represent STZ rats. (PDF 27.3 kb)
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Sookwong, P., Nakagawa, K., Fujita, I. et al. Amadori-Glycated Phosphatidylethanolamine, a Potential Marker for Hyperglycemia, in Streptozotocin-Induced Diabetic Rats. Lipids 46, 943–952 (2011). https://doi.org/10.1007/s11745-011-3588-3
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DOI: https://doi.org/10.1007/s11745-011-3588-3