Ang (1-7) protects islet endothelial cells from palmitate-induced apoptosis by AKT, eNOS, p38 MAPK, and JNK pathways

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Biology

Background:

• Palmitate accumulation is linked to beta-cell dysfunction and apoptosis in diabetes.
• Islet endothelial cells play a crucial role in maintaining islet function and integrity.
• Understanding protective mechanisms against lipotoxicity in islet cells is vital for diabetes research.

Purpose of the Study:

• To investigate the protective effect of angiotensin (1-7) [Ang (1-7)] against palmitate-induced apoptosis in islet endothelial cells.
• To elucidate the underlying molecular mechanisms, including signaling pathways and reactive oxygen species (ROS) production.

Main Methods:

• MS-1 islet endothelial cells were treated with palmitate and Ang (1-7).
• Apoptosis was assessed using DNA fragmentation and flow cytometry.
• ROS production was measured via a ROS Assay Kit.
• Protein expression and phosphorylation of AKT, eNOS, JNK, and p38 were analyzed by western blotting.
• Specific pathway inhibitors (PI3K/AKT, eNOS, p38 MAPK, JNK) were used to confirm mechanisms.

Main Results:

• Ang (1-7) significantly reduced palmitate-induced apoptosis in MS-1 cells.
• Ang (1-7) increased the phosphorylation of AKT and eNOS, counteracting palmitate's inhibitory effects.
• Ang (1-7) inhibited palmitate-induced ROS production and attenuated JNK and p38 activation.
• Inhibitors of PI3K/AKT, eNOS, p38 MAPK, and JNK pathways blocked the anti-apoptotic effects of Ang (1-7).

Conclusions:

• Angiotensin (1-7) demonstrates a significant protective effect against palmitate-induced apoptosis in islet endothelial cells.
• The protective mechanism involves the AKT/eNOS/NO signaling pathway and the modulation of JNK and p38 pathways.
• Ang (1-7) may represent a novel therapeutic strategy for preserving islet endothelial cell function in conditions of lipotoxicity.