Ultra-structural study of insulin granules in pancreatic β-cells of db/db mouse by scanning transmission electron microscopy tomography

Yanhong Xue1, Wei Zhao1, Wen Du1, Xiang Zhang1, Gang Ji1, Wang Ying1, Tao Xu1,2()

PDF(555 KB)
PDF(555 KB)
Protein Cell ›› 2012, Vol. 3 ›› Issue (7) : 521-525. DOI: 10.1007/s13238-012-2937-1
COMMUNICATION
COMMUNICATION

Ultra-structural study of insulin granules in pancreatic β-cells of db/db mouse by scanning transmission electron microscopy tomography

  • Yanhong Xue1, Wei Zhao1, Wen Du1, Xiang Zhang1, Gang Ji1, Wang Ying1, Tao Xu1,2()
Author information +
History +

Abstract

Insulin granule trafficking is a key step in the secretion of glucose-stimulated insulin from pancreatic β-cells. The main feature of type 2 diabetes (T2D) is the failure of pancreatic β-cells to secrete sufficient amounts of insulin to maintain normal blood glucose levels. In this work, we developed and applied tomography based on scanning transmission electron microscopy (STEM) to image intact insulin granules in the β-cells of mouse pancreatic islets. Using three-dimensional (3D) reconstruction, we found decreases in both the number and the grey level of insulin granules in db/db mouse pancreatic β-cells. Moreover, insulin granules were closer to the plasma membrane in diabetic β-cells than in control cells. Thus, 3D ultra-structural tomography may provide new insights into the pathology of insulin secretion in T2D.

Keywords

insulin / secretory granule / diabetes / stem / tomography / 3D reconstructionb

Cite this article

Download citation ▾
Yanhong Xue, Wei Zhao, Wen Du, Xiang Zhang, Gang Ji, Wang Ying, Tao Xu. Ultra-structural study of insulin granules in pancreatic β-cells of db/db mouse by scanning transmission electron microscopy tomography. Prot Cell, 2012, 3(7): 521‒525 https://doi.org/10.1007/s13238-012-2937-1

References

[1] Barg, S., Eliasson, L., Renstrom, E., and Rorsman, P. (2002). A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse beta- cells. Diabetes 51Suppl 1, S74-82 .10.2337/diabetes.51.2007.S74
[2] Boquist, L., Hellman, B., Lernmark, A., and Taljedal, I.B. (1974). Influence of the mutation "diabetes" on insulin release and islet morphology in mice of different genetic backgrounds. J Cell Biol 62, 77-89 .10.1083/jcb.62.1.77
[3] Dean, P.M. (1973). Ultrastructural morphometry of the pancreatic-cell. Diabetologia 9, 115-119 .10.1007/BF01230690
[4] Diani, A.R., Peterson, T., Sawada, G.A., Wyse, B.M., Gilchrist, B.J., Hearron, A.E., and Chang, A.Y. (1984). Ciglitazone, a new hypoglycaemic agent. 4. Effect on pancreatic islets of C57BL/6J-ob/ob and C57BL/KsJ-db/db mice. Diabetologia 27, 225-234 .
[5] Leiter, E.H., Coleman, D.L., and Eppig, J.J. (1979). Endocrine pancreatic cells of postnatal "diabetes" (db) mice in cell culture. In Vitro 15, 507-521 .10.1007/BF02618153
[6] Nagamatsu, S., Nakamichi, Y., Yamamura, C., Matsushima, S., Watanabe, T., Ozawa, S., Furukawa, H., and Ishida, H. (1999). Decreased expression of t-SNARE, syntaxin 1, and SNAP-25 in pancreatic beta-cells is involved in impaired insulin secretion from diabetic GK rat islets: restoration of decreased t-SNARE proteins improves impaired insulin secretion. Diabetes 48, 2367-2373 .10.2337/diabetes.48.12.2367
[7] Nakamura, M., Kitamura, H., Konishi, S., Nishimura, M., Ono, J., Ina, K., Shimada, T., and Takaki, R. (1995). The endocrine pancreas of spontaneously diabetic db/db mice: microangiopathy as revealed by transmission electron microscopy. Diabetes Res Clin Pract 30, 89-100 .10.1016/0168-8227(95)01155-2
[8] Olofsson, C.S., Gopel, S.O., Barg, S., Galvanovskis, J., Ma, X., Salehi, A., Rorsman, P., and Eliasson, L. (2002). Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells. Pflugers Arch 444, 43-51 .10.1007/s00424-002-0781-5
[9] Ostenson, C.G., Gaisano, H., Sheu, L., Tibell, A., and Bartfai, T. (2006). Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide attachment protein receptor complex proteins in pancreatic islets of type 2 diabetic patients. Diabetes 55, 435-440 .10.2337/diabetes.55.02.06.db04-1575
[10] Ostenson, C.G., Khan, A., Abdel-Halim, S.M., Guenifi, A., Suzuki, K., Goto, Y., and Efendic, S. (1993). Abnormal insulin secretion and glucose metabolism in pancreatic islets from the spontaneously diabetic GK rat. Diabetologia 36, 3-8 .10.1007/BF00399086
[11] Porter, A.E., Gass, M., Muller, K., Skepper, J.N., Midgley, P.A., and Welland, M. (2007). Direct imaging of single-walled carbon nanotubes in cells. Nat Nanotechnol 2, 713-717 .10.1038/nnano.2007.347
[12] Porter, A.E., Muller, K., Skepper, J., Midgley, P., and Welland, M. (2006). Uptake of C60 by human monocyte macrophages, its localization and implications for toxicity: studied by high resolution electron microscopy and electron tomography. Acta Biomater 2, 409-419 .10.1016/j.actbio.2006.02.006
[13] Portha, B., Giroix, M.H., Serradas, P., Welsh, N., Hellerstrom, C., Sener, A., and Malaisse, W.J. (1988). Insulin production and glucose metabolism in isolated pancreatic islets of rats with NIDDM. Diabetes 37, 1226-1233 .10.2337/diabetes.37.9.1226
[14] Rorsman, P., Eliasson, L., Renstrom, E., Gromada, J., Barg, S., and Gopel, S. (2000). The Cell Physiology of Biphasic Insulin Secretion. News Physiol Sci 15, 72-77 .
[15] Rorsman, P., and Renstrom, E. (2003). Insulin granule dynamics in pancreatic beta cells. Diabetologia 46, 1029-1045 .10.1007/s00125-003-1153-1
[16] Sougrat, R., Bartesaghi, A., Lifson, J.D., Bennett, A.E., Bess, J.W., Zabransky, D.J., and Subramaniam, S. (2007). Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry. PLoS Pathog 3, e63.10.1371/journal.ppat.0030063
[17] Suckale, J., and Solimena, M. (2008). Pancreas islets in metabolic signaling—focus on the beta-cell. Front Biosci 13, 7156-7171 .10.2741/3218
[18] Suckale, J., and Solimena, M. (2010). The insulin secretory granule as a signaling hub. Trends Endocrinol Metab 21, 599-609 .10.1016/j.tem.2010.06.003
[19] Yakushevska, A.E., Lebbink, M.N., Geerts, W.J., Spek, L., van Donselaar, E.G., Jansen, K.A., Humbel, B.M., Post, J.A., Verkleij, A.J., and Koster, A.J. (2007). STEM tomography in cell biology. J Struct Biol 159, 381-391 .10.1016/j.jsb.2007.04.006
AI Summary AI Mindmap
PDF(555 KB)

Accesses

Citations

Detail

Sections
Recommended

/