Reduced synchroneity of intra-islet Ca2+ oscillations in vivo in Robo-deficient β cells

Elife. 2021 Jul 7;10:e61308. doi: 10.7554/eLife.61308.

Abstract

The spatial architecture of the islets of Langerhans is hypothesized to facilitate synchronized insulin secretion among β cells, yet testing this in vivo in the intact pancreas is challenging. Robo βKO mice, in which the genes Robo1 and Robo2 are deleted selectively in β cells, provide a unique model of altered islet spatial architecture without loss of β cell differentiation or islet damage from diabetes. Combining Robo βKO mice with intravital microscopy, we show here that Robo βKO islets have reduced synchronized intra-islet Ca2+ oscillations among β cells in vivo. We provide evidence that this loss is not due to a β cell-intrinsic function of Robo, mis-expression or mis-localization of Cx36 gap junctions, or changes in islet vascularization or innervation, suggesting that the islet architecture itself is required for synchronized Ca2+ oscillations. These results have implications for understanding structure-function relationships in the islets during progression to diabetes as well as engineering islets from stem cells.

Keywords: beta cells; cell biology; developmental biology; intravital microscopy; islet architecture; islets of Langerhans; mouse; robo receptors; synchronous insulin secretion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Connexins / genetics
  • Connexins / metabolism
  • Gap Junctions / metabolism
  • Insulin Secretion / physiology*
  • Insulin-Secreting Cells / physiology*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / drug effects*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Receptors, Immunologic / deficiency*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*

Substances

  • Connexins
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • Robo2 protein, mouse
  • connexin 36
  • roundabout protein