Presence of glyceraldehyde-derived advanced glycation end-products in the liver of insulin-resistant mice.
Insulin resistance is a fundamental feature of metabolic disorders such as metabolic syndrome. The formation of advanced glycation end-products (AGEs) is increased in patients with hyperglycemia, which results in the loss of protein function. Therefore, considerable attention has been paid to the pathological significance of AGEs in diseases associated with insulin resistance. We previously demonstrated that all-trans-retinoic acid (ATRA) ameliorated insulin resistance in mice that were fed a high-fat, high-fructose (HFHFr) diet. However, it is unclear whether the HFHFr diet increases the production of AGEs in the liver, and whether ATRA affects this production. In the present study, we investigated the production of glyceraldehyde-derived AGEs (Glycer-AGEs) in the liver of HFHFr diet-induced insulin-resistant mice using an antibody against Glycer-AGEs. We noted a remarkable formation of Glycer-AGEs with estimated molecular weights of approximately 265, 282, and 312 kDa in the liver of the insulin-resistant mice; however, the production of Glycer-AGEs was limited in the control. In accordance with previous observations, these Glycer-AGEs in mice disappeared after treatment with ATRA. These results suggest that hepatic Glycer-AGEs can be useful markers for the diagnosis and therapeutic evaluation of insulin resistance and may play a pathological role in the development of insulin resistance.
Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Japan.
Yu
Y
Ebata
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hiroshima International University, Japan.
Junichi
J
Takino
Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Japan, and Departments of Medicine and Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Hiroyuki
H
Tsuchiya
Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan.
Tomohiko
T
Sakabe
Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Japan.
Yoshito
Y
Ikeda
Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Japan.
Susumu
S
Hama
Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Japan.
Kentaro
K
Kogure
Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.
Masayoshi
M
Takeuchi
Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan.
Goshi
G
Shiota
D000818:Animals; D017127:Glycation End Products, Advanced / Q000032:analysis*; D005985:Glyceraldehyde / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D014212:Tretinoin / Q000494:pharmacology
D017127:Glycation End Products, Advanced; D005985:Glyceraldehyde; D014212:Tretinoin
advanced glycation end-products; all-trans-retinoic acid; fructose; glyceraldehyde; insulin resistance