Reversible changes in pancreatic islet structure and function produced by elevated blood glucose

Melissa F. Brereton, Michaela Iberl, Kenju Shimomura, Quan Zhang, Alice E. Adriaenssens, Peter Proks, Ioannis I. Spiliotis, William Dace, Katia K. Mattis, Reshma Ramracheya, Fiona M. Gribble, Frank Reimann, Anne Clark, Patrick Rorsman, Frances M. Ashcroft

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Diabetes is characterized by hyperglycaemia due to impaired insulin secretion and aberrant glucagon secretion resulting from changes in pancreatic islet cell function and/or mass. The extent to which hyperglycaemia per se underlies these alterations remains poorly understood. Here we show that Î 2-cell-specific expression of a human activating K ATP channel mutation in adult mice leads to rapid diabetes and marked alterations in islet morphology, ultrastructure and gene expression. Chronic hyperglycaemia is associated with a dramatic reduction in insulin-positive cells and an increase in glucagon-positive cells in islets, without alterations in cell turnover. Furthermore, some Î 2-cells begin expressing glucagon, whilst retaining many Î 2-cell characteristics. Hyperglycaemia, rather than K ATP channel activation, underlies these changes, as they are prevented by insulin therapy and fully reversed by sulphonylureas. Our data suggest that many changes in islet structure and function associated with diabetes are attributable to hyperglycaemia alone and are reversed when blood glucose is normalized.

Original languageEnglish
Article number4639 (2014)
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 22 Aug 2014

Keywords

  • Diabetes
  • Islets of Langerhans
  • Mechanisms of disease

Fingerprint Dive into the research topics of 'Reversible changes in pancreatic islet structure and function produced by elevated blood glucose'. Together they form a unique fingerprint.

  • Cite this

    Brereton, M. F., Iberl, M., Shimomura, K., Zhang, Q., Adriaenssens, A. E., Proks, P., Spiliotis, I. I., Dace, W., Mattis, K. K., Ramracheya, R., Gribble, F. M., Reimann, F., Clark, A., Rorsman, P., & Ashcroft, F. M. (2014). Reversible changes in pancreatic islet structure and function produced by elevated blood glucose. Nature Communications, 5, [4639 (2014)]. https://doi.org/10.1038/ncomms5639