Modulatory effects of gangliosides on pancreas B-cells regeneration factors in non-obese diabetic (NOD) mice

Abstract

NOD (non-obese diabetic) mice are a very useful and important tool for autoimmune type 1 diabetes (DM-1) studies. Until approximately 3-4 weeks of life, histological studies have shown a progressive migration of immune cells to the pancreas islets. These cells surround the islet (peri-insulitis) without significant b-cell destruction. In the subsequent weeks, the infiltrating immune cells gradually invade the islet (insulitis) leading, in most of the female NOD mice, to severe insulitis and insulin-producing cell damage and overt diabetes. Our previous works show the immune modulation of gangliosídeos in experimental model of DM-1 and Experimental autoimmune encephalitis (EAE). However, the mechanisms for which these substances exert such function are elucidated. Gangliosides constitute a heterogeneous family of sialic acid-containing glycosphingolipids found as normal cell membrane components. These compounds can be found in the majority of cellular types, but with a relative abundance in the nervous system where they influence the development and/or differentiation of neurons. The effects of gangliosides on inflammatory modulation could be related to the process of cell regeneration as well, opening a new perspective for its use in therapeutically strategies aiming the control of beta cell immune aggression and support the regenerating factors release. In the present study, serum, pancreas islets cells from NOD mice treated from 4th to 30th week of life with monosialic ganglioside GM1 (100 mg/kg/day), ganglioside mixture (GM1, GD1a, GD1b, GT1b, 150 mg/kg/Day) and the group control which received saline solution, were isolated to investigate the integrity, b-cell mass, regeneration factors gene expression and protein release. (AU)