Linagliptin Ameliorates Hepatic Steatosis via Non-Canonical Mechanisms in Mice Treated with a Dual Inhibitor of Insulin Receptor and IGF-1 Receptor
Abstract
:1. Introduction
2. Results
2.1. Linagliptin Reduced Plasma Triglyceride Levels without Altering Blood Glucose and Serum Insulin Levels in OSI-906-Treated Mice
2.2. Linagliptin Improved OSI-906-Induced Hepatic Steatosis
2.3. Hepatic Proteomic and Phosphoproteomic Analyses Revealed Insulin- and Glucose-Independent Effects of Linagliptin in OSI-906-Induced Hepatic Steatosis
2.4. Linagliptin Exerts Direct and Indirect Effects on Hepatocytes during the Improvement of Hepatic Steatosis
3. Discussion
4. Materials and Methods
4.1. Animals and Animal Care
4.2. Drugs
4.3. Biochemical Parameters
4.4. Histological Analysis
4.5. Real-Time PCR
4.6. Immunoblotting and Immunopricipitation
4.7. Cell Culture
4.8. Sample Preparation for LC-MS/MS
4.9. Proteomic and Phosphoproteomic Analyses
4.10. IPA Functional Enrichment Analysis
4.11. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
DIO | Diet-induced obesity |
DPP-4 | Dipeptidyl peptidase-4 |
IGF1R | IGF-1 receptor |
IR | Insulin receptor |
NAFLD | Non-alcoholic fatty liver disease |
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Okuyama, T.; Shirakawa, J.; Tajima, K.; Ino, Y.; Vethe, H.; Togashi, Y.; Kyohara, M.; Inoue, R.; Miyashita, D.; Li, J.; et al. Linagliptin Ameliorates Hepatic Steatosis via Non-Canonical Mechanisms in Mice Treated with a Dual Inhibitor of Insulin Receptor and IGF-1 Receptor. Int. J. Mol. Sci. 2020, 21, 7815. https://doi.org/10.3390/ijms21217815
Okuyama T, Shirakawa J, Tajima K, Ino Y, Vethe H, Togashi Y, Kyohara M, Inoue R, Miyashita D, Li J, et al. Linagliptin Ameliorates Hepatic Steatosis via Non-Canonical Mechanisms in Mice Treated with a Dual Inhibitor of Insulin Receptor and IGF-1 Receptor. International Journal of Molecular Sciences. 2020; 21(21):7815. https://doi.org/10.3390/ijms21217815
Chicago/Turabian StyleOkuyama, Tomoko, Jun Shirakawa, Kazuki Tajima, Yoko Ino, Heidrun Vethe, Yu Togashi, Mayu Kyohara, Ryota Inoue, Daisuke Miyashita, Jinghe Li, and et al. 2020. "Linagliptin Ameliorates Hepatic Steatosis via Non-Canonical Mechanisms in Mice Treated with a Dual Inhibitor of Insulin Receptor and IGF-1 Receptor" International Journal of Molecular Sciences 21, no. 21: 7815. https://doi.org/10.3390/ijms21217815