AUTHOR=Petrovic Ivica , Pejnovic Nada , Ljujic Biljana , Pavlovic Sladjana , Miletic Kovacevic Marina , Jeftic Ilija , Djukic Aleksandar , Draginic Nevena , Andjic Marijana , Arsenijevic Nebojsa , Lukic Miodrag L. , Jovicic Nemanja 

TITLE=Overexpression of Galectin 3 in Pancreatic β Cells Amplifies β-Cell Apoptosis and Islet Inflammation in Type-2 Diabetes in Mice

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00030

DOI=10.3389/fendo.2020.00030

ISSN=1664-2392

ABSTRACT=Aims/hypothesis: Galectin 3 appears to have 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 hematopoetic cells-derived galectin 3 induces insulin resistence. 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 expression of this molecule on the target pancreatic beta cells is not defined. 
Methods: To clarify the role of galectin 3 expression in beta cells during obesity-induced diabetogenesis, we developed transgenic mice selectively overexpressing galectin 3 in beta cells, and tested their suceptibility to obesity induced type 2 diabetes. 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.
Results: Our results demonstrated that 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. 
Conclusions/interpretation: 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.