Abstract
BackgroundInsulin producing beta cell and glucagon producing alpha cells are colocalized in pancreatic islets in an arrangement that facilitates the coordinated release of the two principal hormones that regulate glucose homeostasis and prevent both hypoglycemia and diabetes. However, this intricate organization has also complicated the determination of the cellular source(s) of the expression of genes that are detected in the islet. This reflects a significant gap in our understanding of mouse islet physiology, which reduces the effectiveness by which mice model human islet disease.ResultsTo overcome this challenge, we generated a bitransgenic reporter mouse that faithfully labels all beta and alpha cells in mouse islets to enable FACS-based purification and the generation of comprehensive transcriptomes of both populations. This facilitates systematic comparison across thousands of genes between the two major endocrine cell types of the islets of Langerhans whose principal hormones are of cardinal importance for glucose homeostasis. Our data leveraged against similar data for human beta cells reveal a core common beta cell transcriptome of 9900+ genes. Against the backdrop of overall similar beta cell transcriptomes, we describe marked differences in the repertoire of receptors and long non-coding RNAs between mouse and human beta cells.ConclusionsThe comprehensive mouse alpha and beta cell transcriptomes complemented by the comparison of the global (dis)similarities between mouse and human beta cells represent invaluable resources to boost the accuracy by which rodent models offer guidance in finding cures for human diabetes.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-620) contains supplementary material, which is available to authorized users.
Highlights
Insulin producing beta cell and glucagon producing alpha cells are colocalized in pancreatic islets in an arrangement that facilitates the coordinated release of the two principal hormones that regulate glucose homeostasis and prevent both hypoglycemia and diabetes
Pancreatic beta and alpha cells are clustered together in pancreatic islets to ensure tight coordination of the secretion of insulin and glucagon, whose opposing actions on hepatic glucose metabolism are essential for glucose homeostasis
Despite the functional juxtaposition of insulin and glucagon, pancreatic beta and alpha cells derive from a common progenitor population that during embryonic development is first uniquely defined by the expression of the basic helix-loop-helix transcription factor neurogenin 3 (Neurog3) [1]
Summary
Insulin producing beta cell and glucagon producing alpha cells are colocalized in pancreatic islets in an arrangement that facilitates the coordinated release of the two principal hormones that regulate glucose homeostasis and prevent both hypoglycemia and diabetes This intricate organization has complicated the determination of the cellular source(s) of the expression of genes that are detected in the islet. Under the influence of lineage-specific sets of transcription factors, Neurog3+ early endocrine progenitors undergo stepwise differentiation along parallel lineages to develop into mature alpha and beta cells [2,3,4,5] It follows that upon completion of their differentiation and maturation, alpha and beta cells, by virtue of the secretion of their signature hormones glucagon and insulin, have adapted to functionally opposing roles in glucose metabolism. It follows that a comprehensive understanding of both the alpha and the beta cell and how they regulate glucose homeostasis through the coordination of their activity quite possibly will hold the key to therapeutic interventions aimed at curbing the current diabetes epidemic
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