Inactivated Lactiplantibacillus plantarum SCS2 Attenuates STZ-Induced Oxidative Stress via the lncRNA MEG3/STIM1 Axis

Type 2 diabetes (T2D) is a major public health concern, and oxidative stress plays a critical role in its pathogenesis. This study investigated the protective effects and underlying mechanisms of pretreatment with inactivated Lactiplantibacillus plantarum SCS2 against oxidative stress in streptozotocin (STZ)-treated INS-1 cells and STZ/high-fat diet (HFD)–induced T2D in C57BL/6J mice. Inactivated L. plantarum SCS2 alleviated oxidative damage in INS-1 cells and delayed T2D development in mice. In vitro, treatment reduced intracellular reactive oxygen species and malondialdehyde levels, enhanced antioxidant enzyme activities, attenuated endoplasmic reticulum (ER) swelling, restored calcium homeostasis and store-operated calcium entry, increased maternally expressed gene 3 (MEG3) and stromal interaction molecule 1 (STIM1) expression, and decreased C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) expression. MEG3 knockdown significantly reduced STIM1 expression, suggesting that MEG3 may regulate STIM1. In vivo, inactivated L. plantarum SCS2 was associated with lower body weight, improved glucose homeostasis, and attenuated pancreatic injury and oxidative stress. It also increased MEG3 and STIM1 expression and suppressed CHOP and GRP78 expression in pancreatic tissue (p < 0.05). These findings suggest that inactivated L. plantarum SCS2 protects against STZ-induced oxidative stress, with protective effects accompanied by increased MEG3 and STIM1 expression, improved calcium homeostasis, and reduced ER stress. MEG3 may contribute to the changes in STIM1 expression, although the underlying molecular mechanism remains unresolved.