title: Development, growth and maintenance of β-cell mass: models are also part of the story.
abstract: Pancreatic β-cells in the islets of Langerhans play a crucial role in regulating glucose homeostasis in the circulation. Loss of β-cell mass or function due to environmental, genetic and immunological factors leads to the manifestation of diabetes mellitus. The mechanisms regulating the dynamics of pancreatic β-cell mass during normal development and diabetes progression are complex. To fully unravel such complexity, experimental and clinical approaches need to be combined with mathematical and computational models. In the natural sciences, mathematical and computational models have aided the identification of key mechanisms underlying the behavior of systems comprising multiple interacting components. A number of mathematical and computational models have been proposed to explain the development, growth and death of pancreatic β-cells. In this review, we discuss some of these models and how their predictions provide novel insight into the mechanisms controlling β-cell mass during normal development and diabetes progression. Lastly, we discuss a handful of the major open questions in the field.
authors.affiliation: Department of Physiology, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.
authors.forename: Anmar
authors.initials: A
authors.lastname: Khadra
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA; Department of Computational Medicine & Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA; Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA. Electronic address: schnells@umich.edu.
authors.forename: Santiago
authors.initials: S
authors.lastname: Schnell
mesh_terms: D048429:Cell Size; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology; D053263:Gene Regulatory Networks; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008954:Models, Biological; D015398:Signal Transduction
chemical_list: D007328:Insulin; D005947:Glucose
keywords: Islet cytoarchitecture; Mathematical models; Pancreatic islet development; β-cell apoptosis; β-cell function; β-cell neogenesis; β-cell proliferation