The role of angiotensin (1-7) in pancreatic β-cell function and survival: A focus on autophagy

The angiotensin-converting enzyme 2/angiotensin (1-7) [Ang (1-7)]/Mas axis is recognized for its beneficial impact on pancreatic beta-cell function and survival. However, the precise mechanisms underlying these benefits remain incompletely elucidated. This study aimed to elucidate the role of Ang (1-7) in pancreatic beta-cells and determine whether autophagy is a critical factor in this mechanism. MIN6 cells were treated with palmitate and subjected to interventions including Ang (1-7), A779, and autophagy inhibitors. Cell viability was measured using the CCK-8 assay, and reactive oxygen species levels were quantified. Protein expression related to endoplasmic reticulum (ER) stress and autophagy was evaluated by western blotting. Apoptosis was analyzed using flow cytometry. Ang (1-7) reduced the expression of cleaved caspase-3 and P62, while increasing the expression of Beclin-1 in islets. Furthermore, palmitate treatment significantly elevated reactive oxygen species levels and upregulated the expression of ER stress markers such as GRP78, CHOP, ATF4, PERK, and p-eIF2 alpha. Importantly, Ang (1-7) effectively mitigated these responses. Functionally, Ang (1-7) enhanced the viability and reduced the apoptotic rate of MIN6 cells exposed to palmitate. Mechanistically, Ang (1-7) alleviated ER stress, restored autophagic flux, and stimulated autophagy, as evidenced by increased expression of LC3-II and Beclin-1, and reduced p62 accumulation. These findings underscore that Ang (1-7) promotes the survival of MIN6 cells by restoring autophagic flux and enhancing autophagy.