Abstract
AimTo characterise changes in pancreatic beta cell mass during the development of diabetes in untreated male C57BLKS/J db/db mice. MethodsBlood 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. ResultsTotal 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/InterpretationThe 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.
Highlights
In recent decades obesity and type 2 diabetes (T2D) have raised increasing concern worldwide due to their alarming rise in prevalence [1,2]
Hyperglycaemia was reached in mice at 8 weeks of age with a mean fasted blood glucose value of 10.8 ± 1.2 mM
The present study investigated changes in beta cell dynamics and blood glucose levels in groups of young to old male C57BLKS/J db/db mice in order to characterise changes in pancreatic beta cell mass during the development of glucose intolerance in this widely used type 2 diabetes animal model
Summary
In recent decades obesity and type 2 diabetes (T2D) have raised increasing concern worldwide due to their alarming rise in prevalence [1,2]. Today about 347 million people globally are diabetic [2]. This number is estimated to increase to about 439 million by 2030 with the highest rise occurring in developing countries [1,2]. Studies in rodents suggest that pancreatic beta cells have the capacity to compensate for an increased metabolic load and insulin demand by increasing the beta cell mass and function in order to maintain normal blood glucose [9,10,11]. When the metabolic demands exceed the compensatory capacity of the increased beta cell mass and insulin secretion, hyperglycaemia and T2D will develop [5,12,13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
