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Scientific article
Open access
English

Dynamic uni- and multicellular patterns encode biphasic activity in pancreatic islets

Published inDiabetes, vol. 70, no. 4, p. 878-888
Publication date2021
Abstract

Biphasic secretion is an autonomous feature of many endocrine micro-organs to fulfill physiological demands. The biphasic activity of islet β-cells maintains glucose homeostasis and is altered in type-2 diabetes. Nevertheless, underlying cellular or multicellular functional organizations are only partially understood. High-resolution non-invasive multi-electrode array recordings permit simultaneous analysis of recruitment, of single-cell and of coupling activity within entire islets in long-time experiments. Using this approach, we addressed the organizational modes of both, 1st and 2nd phase, in mouse and human islets under physiological and pathophysiological conditions. Our data provide a new uni- and multicellular model of islet β-cell activation: during the 1st phase, small but highly active β-cell clusters are dominant, whereas during the 2nd phase electrical coupling generates large functional clusters via multicellular slow potentials to favor an economic sustained activity. Post-prandial levels of glucagon-like peptide-1 (GLP-1) favor coupling only in the 2nd phase, whereas aging and glucotoxicity alter coupled activity in both phases. In summary, biphasic activity is encoded upstream of vesicle pools at the micro-organ level by multicellular electrical signals and their dynamic synchronization between β-cells. The profound alteration of the electrical organization of islets in pathophysiological conditions may contribute to functional deficits in type-2 diabetes.

Keywords
  • Animals
  • Diabetes Mellitus
  • Type 2 / metabolism*
  • Electrophysiology
  • Glucagon-Like Peptide 1 / metabolism
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion / genetics
  • Insulin Secretion / physiology
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / metabolism*
  • Male
  • Mice
  • Mice
  • Inbred C57BL
  • Postprandial Period
Citation (ISO format)
JAFFREDO, Manon et al. Dynamic uni- and multicellular patterns encode biphasic activity in pancreatic islets. In: Diabetes, 2021, vol. 70, n° 4, p. 878–888. doi: 10.2337/db20-0214
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Identifiers
ISSN of the journal0012-1797
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