Optical clearing of the pancreas for visualization of mature β-cells and vessels in mice

Islets. 2018 May 4;10(3):e1451282. doi: 10.1080/19382014.2018.1451282. Epub 2018 Apr 4.

Abstract

Glucose metabolism is regulated by insulin, which is produced from β-cells in the pancreas. Because insulin is secreted into vessels in response to blood glucose, vascular structures of the pancreas, especially the relationship between vessels and β-cells, are important for physiological and pathological glucose metabolism. Here, we developed a system to visualize vessels surrounding mature β-cells expressing transcription factor MafA in a three-dimensional manner. Optical clearing of the pancreas prevented light scattering of fluorescence driven by the bacterial artificial chromosome (BAC)-mafA promoter in β-cells. Reconstruction of confocal images demonstrated mature β-cells and the glomerular-like structures of β-cell vasculatures labeled with DyLight 488-conjugated lectin in normal mice as well as in low-dose streptozotocin-injected diabetes model mice with reduced β-cell mass. This technological innovation of organ imaging can be used to investigate morphological changes in vascular structures during transplantation, regeneration and diabetes development.

Keywords: MafA; diabetes; imaging; islets; optical clearing; vascular structure; β-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / diagnostic imaging*
  • Diabetes Mellitus, Experimental / metabolism
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism*
  • Maf Transcription Factors, Large / metabolism
  • Mice
  • Optical Imaging / methods*
  • Pancreas / diagnostic imaging*
  • Pancreas / metabolism

Substances

  • Blood Glucose
  • Insulin
  • Maf Transcription Factors, Large
  • Mafa protein, mouse

Grants and funding

This study was supported by Japan Society for the Promotion of Science (JSPS) JP16H01647 (Scientific Research on Innovative Area “Living in Space”), JSPS JP26461351, JSPS JP17K09843, and grants from the Okinaka Memorial Institute for Medical Research, Japan Diabetes Foundation, IUHW Research Grant and Novartis Pharma Research Grants to W.N.