Overexpression of galectin 3 in pancreatic beta cells amplifies beta cell apoptosis and islet inflammation in type 2 diabetes in mice

Abstract

During obesity hematopoetic cells‐derived galectin 3 induces insulin resistence. While the role of galectin 3 expressed in islet invading immune cells in both type of diabetes has been studied, the importance of expression of this molecule on the target pancreatic beta cells is not defined. We have used 10‐12 weeks old C57/BL6 male mice (WT) and C57/ BL6 mice with transgenically enhanced Gal‐3 expression in pancreatic β cells (TG). Obesity was induced with 16 weeks high fat diet regime. Pancreatic beta cells were tested for susceptibility to apoptosis induced by non‐esterified fatty acids and cytokines as well as parameters of oxidative stress. The overexpression of galectin 3 increases beta cells apoptosis in HFD conditions and increases the percentage of proinflammatory F4/80+ macrophages in islets that express galectin 3 and TLR4. In isolated islets, we have shown that galectin 3 overexpression increases cytokine and palmitate‐triggered beta cells apoptosis and also increases NO2‐ induced oxidative stress of beta cells. Also, in pancreatic lymph nodes, macrophages were shifted towards proinflammatory TNF‐α producing phenotype. By complementary approach in vivo and in vitro, we have shown that galectin 3 overexpression facilitates beta cell damage, enhances cytokine and palmitate‐triggered beta cells apoptosis and also increases NO2‐ induced oxidative stress in beta cells. Further, the results suggest that increased expression of galectin 3 in the pancreatic beta cells affects the metabolism of glucose and glycoregulation in mice on HFD, affecting the fasting glycemic values, as well as glycemia after glucose loading.