Simultaneous monitoring of many functioning β-cells is essential for understanding β-cell dysfunction as an early event in the progression to diabetes. Intrinsic optical signal (IOS) imaging has been shown to allow high resolution detection of stimulus-evoked physiological responses in the retina and other neural tissues. In this paper, we demonstrate the feasibility of using IOS imaging for functional examination of insulin secreting INS-1 cells, a popular model for investigating diabetes associated β-cell dysfunction. Our experiments indicate that IOS imaging permits simultaneous monitoring of glucose-stimulated physiological responses in multiple cells with high spatial (sub-cellular) and temporal (sub-second) resolution. Rapid IOS image sequences revealed transient optical responses that had time courses tightly correlated with the glucose stimulation.

© 2011 OSA

1. W. J. Malaisse, K. Louchami, and A. Sener, “Noninvasive imaging of pancreatic beta cells,” Nat. Rev. Endocrinol 5(7), 394–400 (2009). [CrossRef] [PubMed]
2. S. Wild, G. Roglic, A. Green, R. Sicree, and H. King, “Global prevalence of diabetes: estimates for the year 2000 and projections for 2030,” Diabetes Care 27(5), 1047–1053 (2004). [CrossRef] [PubMed]
3. D. Holmberg and U. Ahlgren, “Imaging the pancreas: from ex vivo to non-invasive technology,” Diabetologia 51(12), 2148–2154 (2008). [CrossRef] [PubMed]
4. M. Villiger, J. Goulley, M. Friedrich, A. Grapin-Botton, P. Meda, T. Lasser, and R. A. Leitgeb, “In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy,” Diabetologia 52(8), 1599–1607 (2009). [CrossRef] [PubMed]
5. M. Villiger, J. Goulley, E. J. Martin-Williams, A. Grapin-Botton, and T. Lasser, “Towards high resolution optical imaging of beta cells in vivo,” Curr. Pharm. Des. 16(14), 1595–1608 (2010). [CrossRef] [PubMed]
6. M. Brissova, M. J. Fowler, W. E. Nicholson, A. Chu, B. Hirshberg, D. M. Harlan, and A. C. Powers, “Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy,” J. Histochem. Cytochem. 53(9), 1087–1097 (2005). [CrossRef] [PubMed]
7. M. Ikeuchi, W. Y. Fujimoto, and D. L. Cook, “Rat islet cells have glucose-dependent periodic electrical activity,” Horm. Metab. Res. 16(3), 125–127 (1984). [CrossRef] [PubMed]
8. C. M. Antunes, A. P. Salgado, L. M. Rosário, and R. M. Santos, “Differential patterns of glucose-induced electrical activity and intracellular calcium responses in single mouse and rat pancreatic islets,” Diabetes 49(12), 2028–2038 (2000). [CrossRef] [PubMed]
9. A. Nittala, S. Ghosh, and X. J. Wang, “Investigating the Role of Islet Cytoarchitecture in Its Oscillation Using a New beta-Cell Cluster Model,” Plos. One 2, (2007). [CrossRef] [PubMed]
10. J. V. Rocheleau, M. S. Remedi, B. Granada, W. S. Head, J. C. Koster, C. G. Nichols, and D. W. Piston, “Critical role of gap junction coupled K-ATP channel activity for regulated insulin secretion,” PLoS Biol. 4(2), 221–227 (2006). [CrossRef]
11. S. Speier, D. Nyqvist, O. Cabrera, J. Yu, R. D. Molano, A. Pileggi, T. Moede, M. Köhler, J. Wilbertz, B. Leibiger, C. Ricordi, I. B. Leibiger, A. Caicedo, and P. O. Berggren, “Noninvasive in vivo imaging of pancreatic islet cell biology,” Nat. Med. 14(5), 574–578 (2008). [CrossRef] [PubMed]
12. J. E. Manning Fox, A. V. Gyulkhandanyan, L. S. Satin, and M. B. Wheeler, “Oscillatory membrane potential response to glucose in islet beta-cells: a comparison of islet-cell electrical activity in mouse and rat,” Endocrinology 147(10), 4655–4663 (2006). [CrossRef] [PubMed]
13. H. H. Harary, J. E. Brown, and L. H. Pinto, “Rapid light-induced changes in near infrared transmission of rods in Bufo marinus,” Science 202(4372), 1083–1085 (1978). [CrossRef] [PubMed]
14. D. R. Pepperberg, M. Kahlert, A. Krause, and K. P. Hofmann, “Photic modulation of a highly sensitive, near-infrared light-scattering signal recorded from intact retinal photoreceptors,” Proc. Natl. Acad. Sci. U.S.A. 85(15), 5531–5535 (1988). [CrossRef] [PubMed]
15. L. B. Cohen, R. D. Keynes, and B. Hille, “Light scattering and birefringence changes during nerve activity,” Nature 218(5140), 438–441 (1968). [CrossRef] [PubMed]
16. A. J. Foust and D. M. Rector, “Optically teasing apart neural swelling and depolarization,” Neuroscience 145(3), 887–899 (2007). [CrossRef] [PubMed]
17. I. Tasaki, A. Watanabe, R. Sandlin, and L. Carnay, “Changes in fluorescence, turbidity, and birefringence associated with nerve excitation,” Proc. Natl. Acad. Sci. U.S.A. 61(3), 883–888 (1968). [CrossRef] [PubMed]
18. Y. G. Li, Q. X. Zhang, L. Liu, F. R. Amthor, and X. C. Yao, “High spatiotemporal resolution imaging of fast intrinsic optical signals activated by retinal flicker stimulation,” Opt. Express 18(7), 7210–7218 (2010). [CrossRef] [PubMed]
19. X. C. Yao and Y. B. Zhao, “Optical dissection of stimulus-evoked retinal activation,” Opt. Express 16(17), 12446–12459 (2008). [CrossRef] [PubMed]
20. Y. C. Li, C. Strang, F. R. Amthor, L. Liu, Y. G. Li, Q. X. Zhang, K. Keyser, and X. C. Yao, “Parallel optical monitoring of visual signal propagation from the photoreceptors to the inner retina layers,” Opt. Lett. 35(11), 1810–1812 (2010). [CrossRef] [PubMed]
21. X. C. Yao, A. Yamauchi, B. Perry, and J. S. George, “Rapid optical coherence tomography and recording functional scattering changes from activated frog retina,” Appl. Opt. 44(11), 2019–2023 (2005). [CrossRef] [PubMed]
22. C. X. Chunming Li, C. Gui, and M. D. Fox, “Level Set Evolution without Re-initialization: A New Variational Formulation,” in Proceeding of IEEE International Conference on Computer Vision and Pattern Recognition (San Diego, 2005), pp. 430–436.
23. M. Wittmann, G. Queisser, A. Eder, J. S. Wiegert, C. P. Bengtson, A. Hellwig, G. Wittum, and H. Bading, “Synaptic activity induces dramatic changes in the geometry of the cell nucleus: interplay between nuclear structure, histone H3 phosphorylation, and nuclear calcium signaling,” J. Neurosci. 29(47), 14687–14700 (2009). [CrossRef] [PubMed]
24. S. Kawauchi, S. Sato, H. Ooigawa, H. Nawashiro, M. Ishihara, and M. Kikuchi, “Simultaneous measurement of changes in light absorption due to the reduction of cytochrome c oxidase and light scattering in rat brains during loss of tissue viability,” Appl. Opt. 47(22), 4164–4176 (2008). [CrossRef] [PubMed]
25. K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, “Optophysiology: depth-resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography,” Proc. Natl. Acad. Sci. U.S.A. 103(13), 5066–5071 (2006). [CrossRef] [PubMed]
26. V. J. Srinivasan, Y. Chen, J. S. Duker, and J. G. Fujimoto, “In vivo functional imaging of intrinsic scattering changes in the human retina with high-speed ultrahigh resolution OCT,” Opt. Express 17(5), 3861–3877 (2009). [CrossRef] [PubMed]
27. T. Akkin, D. Landowne, and A. Sivaprakasam, “Optical coherence tomography phase measurement of transient changes in squid giant axons during activity,” J. Membr. Biol. 231(1), 35–46 (2009). [CrossRef] [PubMed]
28. B. W. Graf, T. S. Ralston, H. J. Ko, and S. A. Boppart, “Detecting intrinsic scattering changes correlated to neuron action potentials using optical coherence imaging,” Opt. Express 17(16), 13447–13457 (2009). [CrossRef] [PubMed]

Appl. Opt.

• X. C. Yao, A. Yamauchi, B. Perry, and J. S. George, “Rapid optical coherence tomography and recording functional scattering changes from activated frog retina,” Appl. Opt. 44(11), 2019–2023 (2005). [CrossRef] [PubMed]
• S. Kawauchi, S. Sato, H. Ooigawa, H. Nawashiro, M. Ishihara, and M. Kikuchi, “Simultaneous measurement of changes in light absorption due to the reduction of cytochrome c oxidase and light scattering in rat brains during loss of tissue viability,” Appl. Opt. 47(22), 4164–4176 (2008). [CrossRef] [PubMed]

Curr. Pharm. Des.

• M. Villiger, J. Goulley, E. J. Martin-Williams, A. Grapin-Botton, and T. Lasser, “Towards high resolution optical imaging of beta cells in vivo,” Curr. Pharm. Des. 16(14), 1595–1608 (2010). [CrossRef] [PubMed]

Diabetes

• C. M. Antunes, A. P. Salgado, L. M. Rosário, and R. M. Santos, “Differential patterns of glucose-induced electrical activity and intracellular calcium responses in single mouse and rat pancreatic islets,” Diabetes 49(12), 2028–2038 (2000). [CrossRef] [PubMed]

Diabetes Care

• S. Wild, G. Roglic, A. Green, R. Sicree, and H. King, “Global prevalence of diabetes: estimates for the year 2000 and projections for 2030,” Diabetes Care 27(5), 1047–1053 (2004). [CrossRef] [PubMed]

Diabetologia

• D. Holmberg and U. Ahlgren, “Imaging the pancreas: from ex vivo to non-invasive technology,” Diabetologia 51(12), 2148–2154 (2008). [CrossRef] [PubMed]
• M. Villiger, J. Goulley, M. Friedrich, A. Grapin-Botton, P. Meda, T. Lasser, and R. A. Leitgeb, “In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy,” Diabetologia 52(8), 1599–1607 (2009). [CrossRef] [PubMed]

Endocrinology

• J. E. Manning Fox, A. V. Gyulkhandanyan, L. S. Satin, and M. B. Wheeler, “Oscillatory membrane potential response to glucose in islet beta-cells: a comparison of islet-cell electrical activity in mouse and rat,” Endocrinology 147(10), 4655–4663 (2006). [CrossRef] [PubMed]

Horm. Metab. Res.

• M. Ikeuchi, W. Y. Fujimoto, and D. L. Cook, “Rat islet cells have glucose-dependent periodic electrical activity,” Horm. Metab. Res. 16(3), 125–127 (1984). [CrossRef] [PubMed]

J. Histochem. Cytochem.

• M. Brissova, M. J. Fowler, W. E. Nicholson, A. Chu, B. Hirshberg, D. M. Harlan, and A. C. Powers, “Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy,” J. Histochem. Cytochem. 53(9), 1087–1097 (2005). [CrossRef] [PubMed]

J. Membr. Biol.

• T. Akkin, D. Landowne, and A. Sivaprakasam, “Optical coherence tomography phase measurement of transient changes in squid giant axons during activity,” J. Membr. Biol. 231(1), 35–46 (2009). [CrossRef] [PubMed]

J. Neurosci.

• M. Wittmann, G. Queisser, A. Eder, J. S. Wiegert, C. P. Bengtson, A. Hellwig, G. Wittum, and H. Bading, “Synaptic activity induces dramatic changes in the geometry of the cell nucleus: interplay between nuclear structure, histone H3 phosphorylation, and nuclear calcium signaling,” J. Neurosci. 29(47), 14687–14700 (2009). [CrossRef] [PubMed]

Nat. Med.

• S. Speier, D. Nyqvist, O. Cabrera, J. Yu, R. D. Molano, A. Pileggi, T. Moede, M. Köhler, J. Wilbertz, B. Leibiger, C. Ricordi, I. B. Leibiger, A. Caicedo, and P. O. Berggren, “Noninvasive in vivo imaging of pancreatic islet cell biology,” Nat. Med. 14(5), 574–578 (2008). [CrossRef] [PubMed]

Nat. Rev. Endocrinol

• W. J. Malaisse, K. Louchami, and A. Sener, “Noninvasive imaging of pancreatic beta cells,” Nat. Rev. Endocrinol 5(7), 394–400 (2009). [CrossRef] [PubMed]

Nature

• L. B. Cohen, R. D. Keynes, and B. Hille, “Light scattering and birefringence changes during nerve activity,” Nature 218(5140), 438–441 (1968). [CrossRef] [PubMed]

Neuroscience

• A. J. Foust and D. M. Rector, “Optically teasing apart neural swelling and depolarization,” Neuroscience 145(3), 887–899 (2007). [CrossRef] [PubMed]

Opt. Express

• Y. G. Li, Q. X. Zhang, L. Liu, F. R. Amthor, and X. C. Yao, “High spatiotemporal resolution imaging of fast intrinsic optical signals activated by retinal flicker stimulation,” Opt. Express 18(7), 7210–7218 (2010). [CrossRef] [PubMed]
• X. C. Yao and Y. B. Zhao, “Optical dissection of stimulus-evoked retinal activation,” Opt. Express 16(17), 12446–12459 (2008). [CrossRef] [PubMed]
• B. W. Graf, T. S. Ralston, H. J. Ko, and S. A. Boppart, “Detecting intrinsic scattering changes correlated to neuron action potentials using optical coherence imaging,” Opt. Express 17(16), 13447–13457 (2009). [CrossRef] [PubMed]
• V. J. Srinivasan, Y. Chen, J. S. Duker, and J. G. Fujimoto, “In vivo functional imaging of intrinsic scattering changes in the human retina with high-speed ultrahigh resolution OCT,” Opt. Express 17(5), 3861–3877 (2009). [CrossRef] [PubMed]

Opt. Lett.

• Y. C. Li, C. Strang, F. R. Amthor, L. Liu, Y. G. Li, Q. X. Zhang, K. Keyser, and X. C. Yao, “Parallel optical monitoring of visual signal propagation from the photoreceptors to the inner retina layers,” Opt. Lett. 35(11), 1810–1812 (2010). [CrossRef] [PubMed]

PLoS Biol.

• J. V. Rocheleau, M. S. Remedi, B. Granada, W. S. Head, J. C. Koster, C. G. Nichols, and D. W. Piston, “Critical role of gap junction coupled K-ATP channel activity for regulated insulin secretion,” PLoS Biol. 4(2), 221–227 (2006). [CrossRef]

Plos. One

• A. Nittala, S. Ghosh, and X. J. Wang, “Investigating the Role of Islet Cytoarchitecture in Its Oscillation Using a New beta-Cell Cluster Model,” Plos. One 2, (2007). [CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

• I. Tasaki, A. Watanabe, R. Sandlin, and L. Carnay, “Changes in fluorescence, turbidity, and birefringence associated with nerve excitation,” Proc. Natl. Acad. Sci. U.S.A. 61(3), 883–888 (1968). [CrossRef] [PubMed]
• K. Bizheva, R. Pflug, B. Hermann, B. Povazay, H. Sattmann, P. Qiu, E. Anger, H. Reitsamer, S. Popov, J. R. Taylor, A. Unterhuber, P. Ahnelt, and W. Drexler, “Optophysiology: depth-resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography,” Proc. Natl. Acad. Sci. U.S.A. 103(13), 5066–5071 (2006). [CrossRef] [PubMed]
• D. R. Pepperberg, M. Kahlert, A. Krause, and K. P. Hofmann, “Photic modulation of a highly sensitive, near-infrared light-scattering signal recorded from intact retinal photoreceptors,” Proc. Natl. Acad. Sci. U.S.A. 85(15), 5531–5535 (1988). [CrossRef] [PubMed]

Science

• H. H. Harary, J. E. Brown, and L. H. Pinto, “Rapid light-induced changes in near infrared transmission of rods in Bufo marinus,” Science 202(4372), 1083–1085 (1978). [CrossRef] [PubMed]

Other

• C. X. Chunming Li, C. Gui, and M. D. Fox, “Level Set Evolution without Re-initialization: A New Variational Formulation,” in Proceeding of IEEE International Conference on Computer Vision and Pattern Recognition (San Diego, 2005), pp. 430–436.

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