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2,7"-Phloroglucinol-6,6'-bieckol protects INS-1 cells against high glucose-induced apoptosis
Hyun-Ah Lee1, Ji-Hyeok Lee2, Ji-Sook Han1
1Department of Food Science and Nutrition, Pusan National University, Busan, 46241, Republic of Korea.
Abstract:
Impaired function and decreasing numbers of pancreatic β cells are key factors in the development of type 2 diabetes. This study investigated whether 2,7″-phloroglucinol-6,6'-bieckol protects INS-1 cells against high glucose-induced glucotoxicity and apoptosis. High glucose (30 mM) treatment led to glucotoxicity and induced apoptosis in INS-1 cells. However, treatment with 10-50 μM 2,7″-phloroglucinol-6,6'-bieckol significantly reduced glucotoxicity (22.4%) and increased cell viability (up to 80.9%). Treatment with 2,7″-phloroglucinol-6,6'-bieckol caused a dose-dependent decrease in intracellular reactive oxygen species, lipid peroxidation, and nitric oxide levels, which are increased in INS-1 cells exposed to high glucose. The level of intracellular reactive oxygen species, lipid peroxidation, and nitric oxide levels in INS-1 cells treated with 30 mM glucose and 50 μM 2,7″-phloroglucinol-6,6'-bieckol (101.9%, 0.11 % and 102.1%) was similar to that of the control group (100%). Furthermore, 2,7″-phloroglucinol-6,6'-bieckol significantly reduced the levels of pro-apoptotic Bax, caspase 9, and caspase 3 proteins, and increased the levels of the anti-apoptotic Bcl-2 protein and poly ADP-ribose polymerase. The Bcl-2/Bax ratio was 6-fold higher in 50 μM 2,7″-phloroglucinol-6,6'-bieckol-treated INS-1 cells than in untreated cells. Apoptotic cells were identified using annexin V/propidium iodide staining, and cells treated with 50 μM 2,7″-phloroglucinol-6,6'-bieckol, the numbers of late apoptotic cells decreased over 2-fold compared to that observed in cells treated with 30 mM glucose. Overall, these results suggest that 2,7″-phloroglucinol-6,6'-bieckol has the potential for use as a pharmaceutical agent to protect pancreatic β cells against high glucose-induced apoptosis.
Insights
This study shows that 2,7″-phloroglucinol-6,6'-bieckol protects pancreatic beta cells from high glucose damage. It reduces cell death and oxidative stress, suggesting potential as a type 2 diabetes therapeutic.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Type 2 diabetes is characterized by impaired pancreatic beta cell function and reduced cell numbers.
- High glucose levels (glucotoxicity) induce apoptosis in pancreatic beta cells, contributing to diabetes progression.
Purpose of the Study:
- To investigate the protective effects of 2,7″-phloroglucinol-6,6'-bieckol against high glucose-induced glucotoxicity and apoptosis in INS-1 cells.
- To evaluate the compound's impact on oxidative stress markers and apoptotic pathways.
Main Methods:
- INS-1 cells were exposed to high glucose (30 mM) with varying concentrations of 2,7″-phloroglucinol-6,6'-bieckol (10-50 μM).
- Assessed cell viability, intracellular reactive oxygen species (ROS), lipid peroxidation, and nitric oxide levels.
- Analyzed protein expression of apoptosis-related factors (Bax, Bcl-2, caspase 3, caspase 9, PARP) and performed Annexin V/propidium iodide staining.
Main Results:
- 2,7″-phloroglucinol-6,6'-bieckol significantly reduced glucotoxicity and increased cell viability in a dose-dependent manner.
- The compound decreased levels of ROS, lipid peroxidation, and nitric oxide to near-control levels.
- It modulated apoptosis by reducing pro-apoptotic proteins (Bax, caspase 9, caspase 3) and increasing anti-apoptotic Bcl-2, leading to a higher Bcl-2/Bax ratio and reduced late apoptotic cells.
Conclusions:
- 2,7″-phloroglucinol-6,6'-bieckol demonstrates significant protective effects against high glucose-induced pancreatic beta cell apoptosis.
- The compound mitigates glucotoxicity by reducing oxidative stress and inhibiting apoptotic pathways.
- These findings suggest its potential as a therapeutic agent for type 2 diabetes.