Characterisation of age-dependent beta cell dynamics in the male db/db mice

PLoS One. 2013 Dec 6;8(12):e82813. doi: 10.1371/journal.pone.0082813. eCollection 2013.

Abstract

Aim: To characterise changes in pancreatic beta cell mass during the development of diabetes in untreated male C57BLKS/J db/db mice.

Methods: Blood samples were collected from a total of 72 untreated male db/db mice aged 5, 6, 8, 10, 12, 14, 18, 24 and 34 weeks, for measurement of terminal blood glucose, HbA1c, plasma insulin, and C-peptide. Pancreata were removed for quantification of beta cell mass, islet numbers as well as proliferation and apoptosis by immunohistochemistry and stereology.

Results: Total pancreatic beta cell mass increased significantly from 2.1 ± 0.3 mg in mice aged 5 weeks to a peak value of 4.84 ± 0.26 mg (P < 0.05) in 12-week-old mice, then gradually decreased to 3.27 ± 0.44 mg in mice aged 34 weeks. Analysis of islets in the 5-, 10-, and 24-week age groups showed increased beta cell proliferation in the 10-week-old animals whereas a low proliferation is seen in older animals. The expansion in beta cell mass was driven by an increase in mean islet mass as the total number of islets was unchanged in the three groups.

Conclusions/interpretation: The age-dependent beta cell dynamics in male db/db mice has been described from 5-34 weeks of age and at the same time alterations in insulin/glucose homeostasis were assessed. High beta cell proliferation and increased beta cell mass occur in young animals followed by a gradual decline characterised by a low beta cell proliferation in older animals. The expansion of beta cell mass was caused by an increase in mean islet mass and not islet number.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Apoptosis
  • Blood Glucose
  • C-Peptide / blood
  • Cell Proliferation
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism
  • Disease Models, Animal
  • Fasting / blood
  • Insulin / blood
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Male
  • Mice

Substances

  • Blood Glucose
  • C-Peptide
  • Insulin

Grant support

The study was funded by Zealand Pharma A/S and Gubra ApS. The funders Zealand Pharma had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Jacob Jelsing and Niels Vrang are the owners of Gubra ApS and contributed with an unbiased and impartial role in the study design and manuscript revision.