Skip to main content

Advertisement

SpringerLink
Log in

Experimental Approaches for High-Resolution In Vivo Imaging of Islet of Langerhans Biology

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Under physiological conditions and in the pathogenesis of diabetes mellitus systemic influences play a substantial role for function and survival of cells of the islet of Langerhans. Therefore, in vivo studies to understand islet biology are indispensible and imaging techniques are increasingly used for this purpose. Among the diverse imaging modalities currently only laser scanning microscopy (LSM) allows resolution and visualization of individual cells and cellular processes. To overcome limited tissue penetration and working distance of LSM and enable in vivo investigations of islet cell physiology, various experimental approaches have been developed. Especially, the recently developed imaging platforms have significantly improved the possibility to study islets at a cellular level in vivo, and provided novel insight into islet biology in health and disease. The various approaches, their applications, and reported results, as well as their limitations are reviewed in this article.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Speier S, Gjinovci A, Charollais A, Meda P, Rupnik M. Cx36-mediated coupling reduces beta-cell heterogeneity, confines the stimulating glucose concentration range, and affects insulin release kinetics. Diabetes. 2007;56:1078–86.

    Article  PubMed  CAS  Google Scholar 

  2. Speier S, Rupnik M. A novel approach to in situ characterization of pancreatic beta-cells. Pflugers Arch. 2003;446:553–8.

    Article  PubMed  CAS  Google Scholar 

  3. Speier S, Yang SB, Sroka K, Rose T, Rupnik M. KATP-channels in beta-cells in tissue slices are directly modulated by millimolar ATP. Mol Cell Endocrinol. 2005;230:51–8.

    Article  PubMed  CAS  Google Scholar 

  4. Ahren B. Autonomic regulation of islet hormone secretion–implications for health and disease. Diabetologia. 2000;43:393–410.

    Article  PubMed  CAS  Google Scholar 

  5. Torres N, Noriega L, Tovar AR. Nutrient modulation of insulin secretion. Vitam Horm. 2009;80:217–44.

    Article  PubMed  CAS  Google Scholar 

  6. Eberhard D, Lammert E. The pancreatic beta-cell in the islet and organ community. Curr Opin Genet Dev. 2009;19:469–75.

    Article  PubMed  CAS  Google Scholar 

  7. Cassidy PJ, Radda GK. Molecular imaging perspectives. J R Soc Interface. 2005;2:133–44.

    Article  PubMed  CAS  Google Scholar 

  8. Malaisse WJ, Louchami K, Sener A. Noninvasive imaging of pancreatic beta cells. Nat Rev Endocrinol. 2009;5:394–400.

    Article  PubMed  CAS  Google Scholar 

  9. Souza F, Freeby M, Hultman K, et al. Current progress in non-invasive imaging of beta cell mass of the endocrine pancreas. Curr Med Chem. 2006;13:2761–73.

    Article  PubMed  CAS  Google Scholar 

  10. Sever D, Eldor R, Sadoun G, et al. Evaluation of impaired beta-cell function in nonobese-diabetic (NOD) mouse model using bioluminescence imaging. Faseb J. 2011;25:676–84.

    Article  PubMed  CAS  Google Scholar 

  11. Virostko J, Radhika A, Poffenberger G, et al. Bioluminescence imaging in mouse models quantifies beta cell mass in the pancreas and after islet transplantation. Mol Imaging Biol. 2010;12:42–53.

    Article  PubMed  Google Scholar 

  12. Leitgeb RA, Villiger M, Bachmann AH, Steinmann L, Lasser T. Extended focus depth for Fourier domain optical coherence microscopy. Opt Lett. 2006;31:2450–2.

    Article  PubMed  CAS  Google Scholar 

  13. Villiger M, Goulley J, Friedrich M, et al. In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy. Diabetologia. 2009;52:1599–607.

    Article  PubMed  CAS  Google Scholar 

  14. Kuhne WaL, A. Ueber die Absonderung des Pankreas. Verhandlungen des Naturhistorisch-Medizinischen Vereins zu Heidelberg 1877;1:445–450.

  15. Mathews A. The changes in structure of the pancreas cell. A consideration of some aspects of cell metabolism. J morphol. 1899;15:171–222.

    Google Scholar 

  16. Covell WP. A microscopic study of pancreatic secretion in the living animal. Anat Rec. 1928;40:213–23.

    Article  Google Scholar 

  17. Brunfeldt K, Hunhammar K, Skouby AP. Studies on the vascular system of the islets of Langerhans in mice. Acta Endocrinol (Copenh). 1958;29:473–80.

    CAS  Google Scholar 

  18. Bunnag SC, Bunnag S, Warner NE. Microcirculation in the islets of Langerhans of the mouse. The Anatomical record. 1963;146:117–23.

    Article  PubMed  CAS  Google Scholar 

  19. McCuskey RS, Chapman TM. Microscopy of the living pancreas in situ. Am J Anat. 1969;126:395–407.

    Article  PubMed  CAS  Google Scholar 

  20. Klar E, Endrich B, Messmer K. Microcirculation of the pancreas. A quantitative study of physiology and changes in pancreatitis. Int J Microcirc Clin Exp. 1990;9:85–101.

    PubMed  CAS  Google Scholar 

  21. Liu YM, Guth PH, Kaneko K, Livingston EH, Brunicardi FC. Dynamic in vivo observation of rat islet microcirculation. Pancreas. 1993;8:15–21.

    Article  PubMed  CAS  Google Scholar 

  22. Ohtani O. Micro-circulation of the pancreas - a correlative study of intravital microscopy with scanning electron-microscopy of vascular corrosion casts. Arch Histol Japon. 1983;46:315–25.

    Article  CAS  Google Scholar 

  23. Hoffmann TF, Uhl E, Messmer K. Protective effect of the somatostatin analogue octreotide in ischemia/reperfusion-induced acute pancreatitis in rats. Pancreas. 1996;12:286–93.

    Article  PubMed  CAS  Google Scholar 

  24. Ludwig R, Kretschmer M, Caspar G, et al. In vivo microscopy of murine islets of Langerhans: increased adhesion of transferred lymphocytes to islets depends on macrophage-derived cytokines in a model of organ-specific insulitis. Immunology. 1999;98:111–5.

    Article  PubMed  CAS  Google Scholar 

  25. Keck T, Campo-Ruiz V, Warshaw AL, et al. Evaluation of morphology and microcirculation of the pancreas by ex vivo and in vivo reflectance confocal microscopy. Pancreatology. 2001;1:48–57.

    Article  PubMed  CAS  Google Scholar 

  26. Speier S, Nyqvist D, Kohler M, et al. Noninvasive high-resolution in vivo imaging of cell biology in the anterior chamber of the mouse eye. Nat Protoc. 2008;3:1278–86.

    Article  PubMed  CAS  Google Scholar 

  27. • Speier S, Nyqvist D, Cabrera O, et al. Noninvasive in vivo imaging of pancreatic islet cell biology. Nat Med 2008;14:574–578. This paper describes the AC platform, using the AC as a transplantation and imaging site for islets of Langerhans. This is currently the only experimental approach that allows noninvasive in vivo imaging of islets at cellular resolution.

    Article  PubMed  CAS  Google Scholar 

  28. • Nyman LR, Wells KS, Head WS, et al. Real-time, multidimensional in vivo imaging used to investigate blood flow in mouse pancreatic islets. J Clin Invest 2008;118:3790–3797. In this article the authors use high-speed confocal LSM to study blood flow direction within the islet of Langerhans inside the pancreas in vivo. The report showed detailed results on the strongly discussed blood flow patterns that are thought to be of functional importance due to the specific anatomical arrangement of the cells within the islet.

    Article  PubMed  CAS  Google Scholar 

  29. Hara M, Wang X, Kawamura T, et al. Transgenic mice with green fluorescent protein-labeled pancreatic beta -cells. Am J Physiol Endocrinol Metab. 2003;284:E177–183.

    PubMed  CAS  Google Scholar 

  30. Nyman LR, Ford E, Powers AC, Piston DW. Glucose-dependent blood flow dynamics in murine pancreatic islets in vivo. Am J Physiol Endocrinol Metab. 2010;298:E807–814.

    Article  PubMed  CAS  Google Scholar 

  31. Reiner T, Kohler RH, Liew CW, et al. Near-infrared fluorescent probe for imaging of pancreatic beta cells. Bioconjug Chem. 2010;21:1362–8.

    Article  PubMed  CAS  Google Scholar 

  32. Fottner C, Mettler E, Goetz M, et al. In vivo molecular imaging of somatostatin receptors in pancreatic islet cells and neuroendocrine tumors by miniaturized confocal laser-scanning fluorescence microscopy. Endocrinology. 2010;151:2179–88.

    Article  PubMed  CAS  Google Scholar 

  33. Martinic MM, von Herrath MG. Real-time imaging of the pancreas during development of diabetes. Immunol Rev. 2008;221:200–13.

    Article  PubMed  CAS  Google Scholar 

  34. Denk W, Strickler JH, Webb WW. Two-photon laser scanning fluorescence microscopy. Science. 1990;248:73–6.

    Article  PubMed  CAS  Google Scholar 

  35. • Coppieters K, Martinic MM, Kiosses WB, Amirian N, von Herrath M. A novel technique for the in vivo imaging of autoimmune diabetes development in the pancreas by two-photon microscopy. PLoS One 2010;5:e15732. This paper describes a sophisticated experimental setup to access islets in the exteriorized pancreas, focusing on environmental control and undisturbed physiology of the islets. The technique enables high-resolution imaging of islet biology under most physiologic conditions over a period of several hours.

    Article  PubMed  CAS  Google Scholar 

  36. Menger MD, Jaeger S, Walter P, et al. Angiogenesis and hemodynamics of microvasculature of transplanted islets of Langerhans. Diabetes. 1989;38 Suppl 1:199–201.

    PubMed  Google Scholar 

  37. Menger MD, Jager S, Walter P, Hammersen F, Messmer K. A novel technique for studies on the microvasculature of transplanted islets of Langerhans in vivo. Int J Microcirc Clin Exp. 1990;9:103–17.

    PubMed  CAS  Google Scholar 

  38. Menger MD, Vajkoczy P, Beger C, Messmer K. Orientation of microvascular blood flow in pancreatic islet isografts. J Clin Invest. 1994;93:2280–5.

    Article  PubMed  CAS  Google Scholar 

  39. Hayek A, Beattie GM, Lopez AD, Chen P. The use of digital image processing to quantitate angiogenesis induced by basic fibroblast growth factor and transplanted pancreatic islets. Microvasc Res. 1991;41:203–9.

    Article  PubMed  CAS  Google Scholar 

  40. Merchant FA, Aggarwal SJ, Diller KR, Bovik AC. In-vivo analysis of angiogenesis and revascularization of transplanted pancreatic islets using confocal microscopy. J Microsc. 1994;176:262–75.

    Article  PubMed  CAS  Google Scholar 

  41. Merchant FA, Diller KR, Aggarwal SJ, Bovik AC. Angiogenesis in cultured and cryopreserved pancreatic islet grafts. Transplantation. 1997;63:1652–60.

    Article  PubMed  CAS  Google Scholar 

  42. Bertera S, Geng X, Tawadrous Z, et al. Body window-enabled in vivo multicolor imaging of transplanted mouse islets expressing an insulin-Timer fusion protein. Biotechniques. 2003;35:718–22.

    PubMed  CAS  Google Scholar 

  43. Christoffersson G, Henriksnas J, Johansson L, et al. Clinical and experimental pancreatic islet transplantation to striated muscle: establishment of a vascular system similar to that in native islets. Diabetes. 2010;59:2569–78.

    Article  PubMed  CAS  Google Scholar 

  44. Gunawardana SC, Benninger RK, Piston DW. Subcutaneous transplantation of embryonic pancreas for correction of type 1 diabetes. Am J Physiol Endocrinol Metab. 2009;296:E323–332.

    Article  PubMed  CAS  Google Scholar 

  45. • Fan Z, Spencer JA, Lu Y, et al. In vivo tracking of 'color-coded' effector, natural and induced regulatory T cells in the allograft response. Nat Med 2010;16:718–722. The article describes the use of endoscopic confocal LSM to repetitively image the infiltration of allogeneic islet grafts under the kidney capsule, allowing a longitudinal assessment of cellular mechanisms during rejection.

    Article  PubMed  CAS  Google Scholar 

  46. Adeghate E. Host-graft circulation and vascular morphology in pancreatic tissue transplants in rats. The Anatomical record. 1998;251:448–59.

    Article  PubMed  CAS  Google Scholar 

  47. Dana MR, Streilein JW. Loss and restoration of immune privilege in eyes with corneal neovascularization. Invest Ophthalmol Vis Sci. 1996;37:2485–94.

    PubMed  CAS  Google Scholar 

  48. Medawar PB. Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol. 1948;29:58–69.

    PubMed  CAS  Google Scholar 

  49. Goldowitz D, Knobler RL, Lublin FD. Heterotopic brain transplants in the study of experimental allergic encephalomyelitis. Exp Neurol. 1987;97:653–61.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No potential conflict of interest relevant to this article was reported.

Author information

Authors and Affiliations

  1. Center for Regenerative Therapies Dresden and Paul Langerhans Institute Dresden, School of Medicine, Dresden University of Technology, 01307, Dresden, Germany

    Stephan Speier

Authors
  1. Stephan Speier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephan Speier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Speier, S. Experimental Approaches for High-Resolution In Vivo Imaging of Islet of Langerhans Biology. Curr Diab Rep 11, 420–425 (2011). https://doi.org/10.1007/s11892-011-0207-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-011-0207-x

Keywords

Search

Navigation