The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Abstract

Regeneration of mature cells that produce functional insulin represents a major focus and a challenge of current diabetes research aimed at restoring beta cell mass in patients with most forms of diabetes, as well as in ageing. The capacity to adapt to diverse physiological states during life and the consequent ability to cope with increased metabolic demands in the normal regulation of glucose homeostasis is a distinctive feature of the endocrine pancreas in mammals. Both beta and alpha cells, and presumably other islet cells, are dynamically regulated via nutrient, neural and/or hormonal activation of growth factor signalling and the post-transcriptional modification of a variety of genes or via the microbiome to continually maintain a balance between regeneration (e.g. proliferation, neogenesis) and apoptosis. Here we review key regulators that determine islet cell mass at different ages in mammals. Understanding the chronobiology and the dynamics and agedependent processes that regulate the relationship between the different cell types in the overall maintenance of an optimally functional islet cell mass could provide important insights into planning therapeutic approaches to counter and/or prevent the development of diabetes.

Pancreas regeneration

“…Despite the lack of substantial islet regeneration in injury models, islet hyperplasia is observed during pregnancy, in obesity, or under insulin resistance conditions in animal models 16–19 . For instance, mouse pancreatic β-cell mass increases by 3–5-fold during pregnancy, stimulated at least partly by the pregnancy hormones placental lactogen and prolactin, and involving signalling through serotonin, Menin, and FoxM1 20–23 .…”

In vivo imaging of beta cells with radiotracers: state of the art, prospects and recommendations for development and use

“…Large changes in pancreas size accompany type 1 diabetes even before clinical diagnosis [34], indicating disease-related changes in the exocrine pancreas of a nature that is not yet understood [34,35]. Although not confirmed in humans, there is evidence for plasticity among islet cell types in metabolically stressed mice [36]. Therefore, the large range of pancreas signal found in PET and SPECT studies of healthy and type 1 diabetes people should not be surprising.…”

Anti-diabetic actions of carbon monoxide-releasing molecule (CORM)-A1: Immunomodulation and regeneration of islet beta cells

“…7,8]. One of potential compounds that could accomplish such requirements is carbon monoxide releasing molecule (CORM)-A1, a sodium boronocarbonate (Na 2 [H 3 BCO 2 ]).…”