Abstract
BackgroundInsulin, the principal regulating hormone of blood glucose, is released through the bursting of the pancreatic islets. Increasing evidence indicates the importance of islet morphostructure in its function, and the need of a quantitative investigation. Recently we have studied this problem from the perspective of islet bursting of insulin, utilizing a new 3D hexagonal closest packing (HCP) model of islet structure that we have developed. Quantitative non-linear dependence of islet function on its structure was found. In this study, we further investigate two key structural measures: the number of neighboring cells that each β-cell is coupled to, nc, and the coupling strength, gc.Resultsβ-cell clusters of different sizes with number of β-cells nβ ranging from 1–343, nc from 0–12, and gc from 0–1000 pS, were simulated. Three functional measures of islet bursting characteristics – fraction of bursting β-cells fb, synchronization index λ, and bursting period Tb, were quantified. The results revealed a hyperbolic dependence on the combined effect of nc and gc. From this we propose to define a dimensionless cluster coupling index or CCI, as a composite measure for islet morphostructural integrity. We show that the robustness of islet oscillatory bursting depends on CCI, with all three functional measures fb, λ and Tb increasing monotonically with CCI when it is small, and plateau around CCI = 1.ConclusionCCI is a good islet function predictor. It has the potential of linking islet structure and function, and providing insight to identify therapeutic targets for the preservation and restoration of islet β-cell mass and function.
Highlights
Insulin, the principal regulating hormone of blood glucose, is released through the bursting of the pancreatic islets
Loss of insulin pulsatility is observed in patients of both type 1 diabetes (T1D) and type 2 diabetes (T2D) [5,7,8], and in relatives with mild glucose intolerance or in individuals at risk for diabetes [9,10,11,12]
A burster is defined as a cell capable of producing a sequence of well-defined regular bursts which correlate with the period between consecutive peaks and nadirs in the calcium signal or membrane action potential
Summary
The principal regulating hormone of blood glucose, is released through the bursting of the pancreatic islets. Quantitative non-linear dependence of islet function on its structure was found. Insulin, secreted by pancreatic islet β-cells, is the principal regulating hormone of glucose metabolism. Plasma insulin exhibits oscillatory characteristics across several time scales independent of changes in plasma glucose [1,2,3,4]. These oscillations are caused by pulsatile insulin secretion [5,6]. The pulsatile insulin release is driven by the electrical burst of β-cell membrane. Single isolated βcells can burst, and can be induced in vitro to release insu-
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.
