ReferenceID 1599
Protection of pancreatic β-cell by phosphocreatine through mitochondrial improvement via the regulation of dual AKT/IRS-1/GSK-3β and STAT3/Cyp-D signaling pathways
Cell Biol Toxicol
Diabetes mellitus (DM) is a metabolic syndrome, caused by insufficient insulin secretion or insulin resistance (IR). DM enhances oxidative stress and induces mitochondrial function in different kinds of cell types, inclu
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Record Fields
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- Reference Id
- 1599
- Evidence Id
- 18189
- Core Evidence Id
- 18189
- Source Reference Id
- 3203
- Herb2 Reference Id
- HBREF004000
- Subject Paper Key
- HBIN021664_34455488
- Pubmed Id
- 34455488
- Doi
- 10.1007/s10565-021-09644-7
- Paper Title
- Protection of pancreatic β-cell by phosphocreatine through mitochondrial improvement via the regulation of dual AKT/IRS-1/GSK-3β and STAT3/Cyp-D signaling pathways
- Paper Abstract
- Diabetes mellitus (DM) is a metabolic syndrome, caused by insufficient insulin secretion or insulin resistance (IR). DM enhances oxidative stress and induces mitochondrial function in different kinds of cell types, including pancreatic beta-cells. Our previous study has showed phosphocreatine (PCr) can advance the mitochondrial function through enhancing the oxidative phosphorylation and electron transport ability in mitochondria damaged by methylglyoxal (MG). Our aim was to explore the potential role of PCr as a molecule to protect mitochondria from diabetes-induced pancreatic beta-cell injury with insulin secretion deficiency or IR through dual AKT/IRS-1/GSK-3beta and STAT3/Cyclophilin D (Cyp-D) signaling pathways. MG-induced INS-1 cell viability, apoptosis, mitochondrial division and fusion, the morphology, and function of mitochondria were suppressed. Flow cytometry was used to detect the production of intracellular reactive oxygen species (ROS) and the changes of intracellular calcium, and the respiratory function was measured by oxygraph-2k. The expressions of AKT, IRS-1, GSK-3beta, STAT3, and Cyp-D were detected using Western blot. The result showed that the oxidative stress-related kinases were significantly restored to the normal level after the pretreatment with PCr. Moreover, PCr pretreatment significantly inhibited cell apoptosis, decreased intracellular calcium, and ROS production, and inhibited mitochondrial division and fusion, and increased ATP synthesis damaged by MG in INS-1 cells. In addition, pretreatment with PCr suppressed Cytochrome C, p-STAT3, and Cyp-D expressions, while increased p-AKT, p-IRS-1, p-GSK-3beta, caspase-3, and caspase-9 expressions. In conclusion, PCr has protective effect on INS-1 cells in vitro and in vivo, relying on AKT mediated STAT3/ Cyp-D pathway to inhibit oxidative stress and restore mitochondrial function, signifying that PCr might become an emerging candidate for the cure of diabetic pancreatic cancer beta-cell damage.
- Journal
- Cell Biol Toxicol
- Publish Year
- 2021
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Diabetes Mellitus; Pancreatic Beta-cell Injury; Insulin Secretion Deficiency; Diabetes; Metabolic Syndrome; Diabetic Pancreatic Cancer
- Paper Title Cn
- Paper Title En
- Protection of pancreatic β-cell by phosphocreatine through mitochondrial improvement via the regulation of dual AKT/IRS-1/GSK-3β and STAT3/Cyp-D signaling pathways
- Bilingual Status
- semi_complete