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

Exp Clin Endocrinol Diabetes. 2023 May;131(5):282-289. doi: 10.1055/a-2044-8873. Epub 2023 Apr 18.

Abstract

Background: In type 2 diabetes, insulin resistance is observed, and β-cells are incapable of responding to glycemia demands, leading to hyperglycemia. Although the nature of β-cells dysfunction in this disease is not fully understood, a link between the induction of pancreatic β-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 β-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-1β and increased pancreatic fibrosis. Finally, the expression of galactosidase-beta 1 (GLB1) was significantly increased in pancreatic β-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.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2*
  • Diet, High-Fat
  • Galactosidases / metabolism
  • Insulin
  • Insulin-Secreting Cells* / metabolism
  • Mice
  • Mice, Inbred C57BL

Substances

  • Blood Glucose
  • Galactosidases
  • Insulin