Phosphocreatine attenuates endoplasmic reticulum stress-mediated hepatocellular apoptosis ameliorates insulin resistance in diabetes model
- Department of Pharmacology, Dalian Medical University, Dalian, Liaoning, 116044 (China)
- Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044 (China)
- Department of Pathology and Forensic Medicine, Dalian Medical University, Dalian, Liaoning, 116044 (China)
Highlights: • PCr decrease blood glucose level improve body weight. • PCr protected liver tissues against STZ/MGO caused apoptosis. • PCr attenuates hepatic endoplasmic reticulum stress markers. • PCr ameliorates insulin resistance. Diabetes mellitus (DM) associated liver damage is a major health burden. Hepatocellular-damage in DM characterized with elevated endoplasmic reticulum stress (ER) and may enhanced insulin-resistance. Phosphocreatine (PCr) a rapidly high-energy-reserve molecule of phosphates naturally occurs in liver, brain and skeletal muscle. This study aimed to investigate the protective effect of PCr on the liver-injury-associated with DM and to report the mechanism involved. Wistar rat's diabetes model was induced using streptozotocin (STZ), and the animals were treated with 20 mg/kg, or 50 mg/kg PCr injection. Blood glucose level, and body wt were recorded. Liver tissues homogenate were analyzed for liver damage markers alanine transaminase (ALT), aspartate transaminase (AST). Liver tissues proteins further evaluated for apoptosis, endoplasmic reticulum stress (ER), and insulin resistance biomarkers using western blotting. Our results revealed that PCr reduced blood glucose level, improved body wt, ameliorates liver function enzymes. Furthermore, PCr upregulates anti-apoptotic Bcl2 proteins expression, and down-regulates significantly pro-apoptotic casp3 and Bax proteins expression in vivo and invitro. Moreover, ER stress CHOP, GRP78 and ATF4 biomarkers level were significantly attenuated in PCr treated animals comparing to STZ diabetes associated liver-damage model with significant improving in insulin-resistance Akt and IRS-1. Our results revealed that treating with PCr in diabetes-associated liver injury models decreased blood glucose level and possess protective effect in-vitro and in-vivo, which could be suggested as potential therapeutic strategy for diabetes associated liver injury patients.
- OSTI ID:
- 23125262
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 506, Issue 3; Other Information: Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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