Biological Sciences Division
Published July 7, 2021 | Version v1
Journal article Open

Reduced synchroneity of intra-islet ca2+ oscillations in vivo in Robo-deficient β cells

Creators

  • 1. University of Wisconsin-Madison
  • 2. University of Colorado Denver
  • 3. Indiana University
  • 4. University of Chicago

Description

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.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

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Additional details

Identifiers

DOI
10.7554/eLife.61308
Other
oai:uchicago.tind.io:10005

Funding

National Institute of Diabetes and Digestive and Kidney Diseases
R01DK121706
National Institute of Diabetes and Digestive and Kidney Diseases
P30DK020579
Institute for Clinical and Translational Research, University of Wisconsin, Madison
UL1TR000427
National Institute of Diabetes and Digestive and Kidney Diseases
R01DK060581
National Institute of Diabetes and Digestive and Kidney Diseases
R01DK102950
National Institute of Diabetes and Digestive and Kidney Diseases
R01DK106412
National Cancer Institute
R01CA216248
National Institute of Diabetes and Digestive and Kidney Diseases
R01DK113103
National Institute on Aging
R01AG062328
American Diabetes Association
ADA 1-16-IBS-212
National Institute of General Medical Sciences
5T32GM007133-44

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Medicine