Molecular Imaging and Biology

, Volume 12, Issue 1, pp 42–53

Bioluminescence Imaging in Mouse Models Quantifies β Cell Mass in the Pancreas and After Islet Transplantation

  • John Virostko
  • Aramandla Radhika
  • Greg Poffenberger
  • Zhongyi Chen
  • Marcela Brissova
  • Joshua Gilchrist
  • Brian Coleman
  • Maureen Gannon
  • E. Duco Jansen
  • Alvin C. Powers
Research Article

DOI: 10.1007/s11307-009-0240-1

Cite this article as:
Virostko, J., Radhika, A., Poffenberger, G. et al. Mol Imaging Biol (2010) 12: 42. doi:10.1007/s11307-009-0240-1
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Abstract

Purpose

We developed a mouse model that enables non-invasive assessment of changes in β cell mass.

Procedures

We generated a transgenic mouse expressing luciferase under control of the mouse insulin I promoter [mouse insulin promoter-luciferase-Vanderbilt University (MIP-Luc-VU)] and characterized this model in mice with increased or decreased β cell mass and after islet transplantation.

Results

Streptozotocin-induced, diabetic MIP-Luc-VU mice had a progressive decline in bioluminescence that correlated with a decrease in β cell mass. MIP-Luc-VU animals fed a high-fat diet displayed a progressive increase in bioluminescence that reflected an increase in β cell mass. MIP-Luc-VU islets transplanted beneath the renal capsule or into the liver emitted bioluminescence proportional to the number of islets transplanted and could be imaged for more than a year.

Conclusions

Bioluminescence in the MIP-Luc-VU mouse model is proportional to β cell mass in the setting of increased and decreased β cell mass and after transplantation.

Key words

Bioluminescence imaging Luciferase Beta cell Pancreatic islet Transplantation Optical imaging Islet mass Beta cell mass Imaging 

Abbreviations

MIP

Mouse insulin promoter

Luc

Luciferase

MIP-Luc-VU

Mouse insulin promoter-luciferase-Vanderbilt University

MRI

Magnetic resonance imaging

PET

Positron emission tomography

BLI

Bioluminescence imaging

pdx1

Pancreatic-duodenal homeobox factor-1

NOD-scid

non-obese diabetic-severe combined immunodeficiency

FVB

Friend leukemia Virus B strain

IBMX

Isobutyl methyl xanthine

STZ

Streptozotocin

ROI

Region of interest

PBS

Phosphate-buffered saline

FBS

Fetal bovine serum

Supplementary material

11307_2009_240_MOESM1_ESM.pdf (57 kb)
Supplementary Figure 1Transgenic mice expressing luciferase under control of a fragment of the pdx1 promoter (pdx1-Luc) emit bioluminescence. a Light emission from pdx1-Luc animals was present throughout the animal, with maximal expression in areas of exposed skin (paws, tail, and nose). bPdx1-Luc islets emitted bioluminescence 3 weeks after transplantation beneath the renal capsule. (PDF 56 kb)
11307_2009_240_MOESM2_ESM.pdf (124 kb)
Supplementary Figure 2Glucose level affects in vitro bioluminescence emission from MIP-Luc-VU islets. Islets were cultured overnight in RPMI with 10% FBS and 2.5, 5.6, 11.0, or 16.7 mM glucose, left to right, and bioluminescence imaging was performed after the addition of luciferin. Islets cultured overnight in higher glucose levels display increased bioluminescence (n = 3). Luciferase activity, as measured by luminometer, also increases with higher glucose concentration (n = 3). (PDF 124 kb)
11307_2009_240_MOESM3_ESM.pdf (30 kb)
Supplementary Figure 3MIP-Luc-VU mice fed a high-fat diet for 6 months (black squares) have reduced glucose clearing (1.5 g/kg body wt) during an intraperitoneal glucose tolerance test compared with animals fed a regular diet (open circles). (PDF 29 kb)
11307_2009_240_MOESM4_ESM.pdf (25 kb)
Supplementary Figure 4BLI of 100 MIP-Luc-VU islets transplanted beneath the renal capsule of an FVB mouse is detected more than 16 months after transplantation. (PDF 24 kb)

Copyright information

© Academy of Molecular Imaging 2009

Authors and Affiliations

  • John Virostko
    • 1
    • 2
  • Aramandla Radhika
    • 3
  • Greg Poffenberger
    • 3
  • Zhongyi Chen
    • 3
  • Marcela Brissova
    • 3
  • Joshua Gilchrist
    • 3
  • Brian Coleman
    • 3
  • Maureen Gannon
    • 3
    • 4
    • 5
  • E. Duco Jansen
    • 2
  • Alvin C. Powers
    • 3
    • 4
    • 6
  1. 1.Vanderbilt University Institute of Imaging ScienceNashvilleUSA
  2. 2.Department of Biomedical EngineeringVanderbilt UniversityNashvilleUSA
  3. 3.Department of Medicine, Division of Diabetes, Endocrinology, and MetabolismVanderbilt UniversityNashvilleUSA
  4. 4.Department of Molecular Physiology and BiophysicsVanderbilt UniversityNashvilleUSA
  5. 5.Department of Cell and Developmental BiologyVanderbilt UniversityNashvilleUSA
  6. 6.VA Tennessee Valley Healthcare SystemNashvilleUSA

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