Increased Galactosidase Beta 1 Expression as a Senescent Key Factor in β-Cells Function Modulation at the Early Steps of Type 2 Diabetes

Background In type 2 diabetes, insulin resistance is observed, and beta-cells are incapable of responding to glycemia demands, leading to hyperglycemia. Although the nature of beta-cells dysfunction in this disease is not fully understood, a link between the induction of pancreatic beta-cell premature senescence and its metabolic implications has been proposed. This study aimed to understand the relationship between diabetes and pancreatic senescence, particularly at the beginning of the disease. Methods C57Bl/6 J mice were fed two different diets, a normal diet and a high-fat diet, for 16 weeks. Pancreatic histomorphology analysis, insulin quantification, inflammation parameters, and senescence biomarkers for the experimental animals were assessed at weeks 12 and 16. Results The results proved that diabetes onset occurred at week 16 in the High Fat Diet group, supported by glycaemia, weight and blood lipid levels. Increased beta-cells size and number accompanied by increased insulin expression were observed. Also, an inflammatory status of the diabetic group was noted by increased levels of systemic IL-1 beta and increased pancreatic fibrosis. Finally, the expression of galactosidase-beta 1 (GLB1) was significantly increased in pancreatic beta-cells. Conclusion The study findings indicate that senescence, as revealed by an increase in GLB1 expression, is a key factor in the initial stage of diabetes.

Automated summary

The study aimed to understand the relationship between diabetes and pancreatic senescence, particularly at the beginning of the disease. The results showed that the induction of pancreatic beta-cell premature senescence is implicated in the onset of diabetes, possibly due to insulin resistance and accumulated pyruvate in beta-cells.