Is β-cell aging involved in the pathogenesis of diabetes?

J Diabetes. 2017 Jul;9(7):707-716. doi: 10.1111/1753-0407.12481. Epub 2016 Oct 29.

Abstract

Background: β-Cells at different stages have different functions and capacity for proliferation, regenerative and apoptosis. The aim of the present study was to investigate whether there are changes in β-cell phonotype in the development of diabetes to identify potential β-cell targets to prevent the progression of diabetes.

Methods: A cross-sectional study was performed on pancreatic tissues obtained from 80 patients classified into three groups: 25 with type 2 diabetes (T2D), 25 with impaired fasting glucose (IFG), and 30 non-diabetics (ND). The ratio of the insulin-positive area to pancreatic area was used as an indirect marker of β-cell mass. Insulin-positive duct cells and scattered β-cells were defined as newly generated β-cells, whereas insulin/neurogenin 3 (Ngn3), insulin/v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA) and insulin/P16 double-positive cells were defined as immature, mature, and senescent β-cells, respectively; Ki67 was used as a marker of cell proliferation, and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) was used as a marker of cell apoptosis. Data were analyzed using the Kruskal-Wallis test.

Results: There were no significant differences in β-cell mass, the prevalence of insulin-positive duct cells, scattered β-cells, or insulin/Ngn3, insulin/MafA, and Insulin/Ki67 double-positive cells among groups. The incidence of insulin/P16 double-positive cells was significantly higher in T2D than ND. β-Cell apoptosis was significantly higher in T2D and IFG than ND.

Conclusion: The senescence and apoptosis of β-cells may be involved in the course of diabetes.

Keywords: 2型糖尿病; apoptosis; pancreatic β-cells; senescence; type 2 diabetes mellitus; 凋亡; 胰腺β细胞; 衰老.

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers / metabolism
  • Blood Glucose / metabolism
  • Cellular Senescence*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Glucose Intolerance / blood
  • Glucose Intolerance / diagnosis
  • Glucose Intolerance / metabolism*
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism*
  • Ki-67 Antigen / metabolism
  • Maf Transcription Factors, Large / metabolism
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / metabolism
  • Retrospective Studies

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • Blood Glucose
  • Insulin
  • Ki-67 Antigen
  • MAFA protein, human
  • Maf Transcription Factors, Large
  • NEUROG3 protein, human
  • Nerve Tissue Proteins