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

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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.

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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

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Acknowledgements

The MIP promoter fragment was graciously provided by Mark Magnuson at Vanderbilt University and the mice were generated in the Vanderbilt Transgenic Mouse/ESC Shared Resource. This study was supported by a grant from the Juvenile Diabetes Research Foundation International, a Merit Review Award from the VA Research Service, the National Institutes of Health (DK68764, DK66636, DK69603, DK63439, DK62641, DK068751, T35DK07383, T32EB001628), the Vanderbilt Mouse Metabolic Phenotyping Center (DK59637), and the Vanderbilt Diabetes Research and Training Center (DK20593). Work performed in the Vanderbilt University Institute of Imaging Science was supported by SAIRP U24 CA126588.

Author information

Authors and Affiliations

  1. Vanderbilt University Institute of Imaging Science, Nashville, TN, USA

    John Virostko

  2. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA

    John Virostko & E. Duco Jansen

  3. Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University, Nashville, TN, USA

    Aramandla Radhika, Greg Poffenberger, Zhongyi Chen, Marcela Brissova, Joshua Gilchrist, Brian Coleman, Maureen Gannon & Alvin C. Powers

  4. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA

    Maureen Gannon & Alvin C. Powers

  5. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA

    Maureen Gannon

  6. VA Tennessee Valley Healthcare System, Nashville, TN, USA

    Alvin C. Powers

Authors
  1. John Virostko
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  2. Aramandla Radhika
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  4. Zhongyi Chen
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  5. Marcela Brissova
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  7. Brian Coleman
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  9. E. Duco Jansen
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  10. Alvin C. Powers
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Corresponding author

Correspondence to Alvin C. Powers.

Additional information

Virostko and Radhika contributed equally to this manuscript.

Electronic supplementary material

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Supplementary Figure 1

Transgenic 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). b Pdx1-Luc islets emitted bioluminescence 3 weeks after transplantation beneath the renal capsule. (PDF 56 kb)

Supplementary Figure 2

Glucose 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)

Supplementary Figure 3

MIP-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)

Supplementary Figure 4

BLI 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)

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Virostko, J., Radhika, A., Poffenberger, G. et al. Bioluminescence Imaging in Mouse Models Quantifies β Cell Mass in the Pancreas and After Islet Transplantation. Mol Imaging Biol 12, 42–53 (2010). https://doi.org/10.1007/s11307-009-0240-1

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  • DOI: https://doi.org/10.1007/s11307-009-0240-1

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