Overexpression of Galectin 3 in Pancreatic ? Cells Amplifies ?-Cell Apoptosis and Islet Inflammation in Type-2 Diabetes in Mice.

ABSTRACT: Aims/Hypothesis: Galectin 3 appears to play a proinflammatory role in several inflammatory and autoimmune diseases. Also, there is evidence that galectin 3 plays a role in both type-1 and type-2 diabetes. During obesity, hematopoietic cell-derived galectin 3 induces insulin resistance. While the role of galectin 3 expressed in islet-invading immune cells in both type-1 and type-2 diabetes has been studied, the importance of the expression of this molecule on the target pancreatic ? cells has not been defined. Methods: To clarify the role of galectin 3 expression in ? cells during obesity-induced diabetogenesis, we developed transgenic mice selectively overexpressing galectin 3 in ? cells and tested their susceptibility to obesity-induced type-2 diabetes. Obesity was induced with a 16-week high-fat diet regime. Pancreatic ? cells were tested for susceptibility to apoptosis induced by non-esterified fatty acids and cytokines as well as parameters of oxidative stress. Results: Our results demonstrated that overexpression of galectin 3 increases ?-cell 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 ?-cell apoptosis and also increases NO_2--induced oxidative stress of ? cells. Also, in pancreatic lymph nodes, macrophages were shifted toward a proinflammatory TNF-?-producing phenotype. Conclusions/Interpretation: By complementary in vivo and in vitro approaches, we have shown that galectin 3-overexpression facilitates ?-cell damage, enhances cytokine and palmitate-triggered ?-cell apoptosis, and increases NO_2--induced oxidative stress in ? cells. Further, the results suggest that increased expression of galectin 3 in the pancreatic ? cells affects the metabolism of glucose and glycoregulation in mice on a high-fat diet, affecting both fasting glycemic values and glycemia after glucose loading.

SUBMITTER: Petrovic I 

PROVIDER: S-EPMC7018709 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature