Abstract
Glycogen is a vital highly branched polymer of glucose that is essential for blood glucose homeostasis. In this article, the structure of liver glycogen from mice is investigated with respect to size distributions, degradation kinetics, and branching structure, complemented by a comparison of normal and diabetic liver glycogen. This is done to screen for differences that may result from disease. Glycogen α-particle (diameter ∼ 150 nm) and β-particle (diameter ∼ 25 nm) size distributions are reported, along with in vitro γ-amylase degradation experiments, and a small angle X-ray scattering analysis of mouse β-particles. Type 2 diabetic liver glycogen upon extraction was found to be present as large loosely bound, aggregates, not present in normal livers. Liver glycogen was found to aggregate in vitro over a period of 20 h, and particle size is shown to be related to rate of glucose release, allowing a structure-function relationship to be inferred for the tissue specific distribution of particle types. Application of branching theories to small angle X-ray scattering data for mouse β-particles revealed these particles to be randomly branched polymers, not fractal polymers. Together, this article shows that type 2 diabetic liver glycogen is present as large aggregates in mice, which may contribute to the inflexibility of interconversion between glucose and glycogen in type 2 diabetes, and further that glycogen particles are randomly branched with a size that is related to the rate of glucose release.
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Ryu, J.H., Drain, J., Kim, J.H., McGee, S., Gray-Weale, A., Waddington, L., Parker, G.J., Hargreaves, M., Yoo, S.H., Stapleton, D.: Int. J. Biol. Macromol. 45(5), 478 (2009). doi:10.1016/j.ijbiomac.2009.08.006
Hers, H.G.: Annu. Rev. Biochem. 45, 167 (1976). doi:10.1146/annurev.bi.45.070176.001123
Roach, P.J., Depaoli-Roach, A.A., Hurley, T.D., Tagliabracci, V.S.: Biochem. J. 441(3), 763 (2012). doi:10.1042/BJ20111416
Sakaida, M., Watanabe, J., Kanamura, S., Tokunaga, H., Ogawa, R.: Anat. Rec. 218(3), 267 (1987). doi:10.1002/ar.1092180307
Drochmans, P.: J. Ultrastruct. Res. 6(2), 141 (1962). doi:10.1016/S0022-5320(62)90050-3
Besford, Q.A., Sullivan, M.A., Zheng, L., Gilbert, R.G., Stapleton, D., Gray-Weale, A.: Int. J. Biol. Macromol. 51(5), 887 (2012). doi:10.1016/j.ijbiomac.2012.06.037
Powell, P.O., Sullivan, M.A., Sheehy, J.J., Schulz, B.L., Warren, F.J., Gilbert, R.G.: PLoS One 10(3), e0121337 (2015). doi:10.1371/journal.pone.0121337
Sullivan, M.A., O’ Connor, M.J., Umana, F., Roura, E., Jack, K., Stapleton, D.I., Gilbert, R.G.: Biomacromolecules 13(11), 3805 (2012). doi:10.1021/bm3012727
Samorajski, T., Keefe, J.R., Ordy, J.M.: Vision Res. 5(1), 639 (1965)
Bathgate, G., Manners, D.: Biochem. J. 101(1), 3 (1966)
Manners, D.J.: Carbohydr. Polym. 16(1), 37 (1991). doi:10.1016/0144-8617(91)90071-J
Sullivan, M.A., Vilaplana, F., Cave, R.A., Stapleton, D., Gray-Weale, A.A., Gilbert, R.G.: Biomacromolecules 11, 1094 (2010)
Meléndez, R., Meléndez-Hevia, E., Cascante, M.: J. Mol. Evol. 45(4), 446 (1997)
Meléndez-Hevia, E., Waddell, T.G., Shelton, E.D.: Biochem. J. 295, 477 (1993)
Meléndez, R., Meléndez-Hevia, E., Canela, E.I.: Biophys. J. 77(3), 1327 (1999). doi:10.1016/S0006-3495(99)76982-1
Konkolewicz, D., Gilbert, R., Gray-Weale, A.: Phys. Rev. Lett. 98(23), 1 (2007). doi:10.1103/PhysRevLett.98.238301
Konkolewicz, D., Thorn-Seshold, O., Gray-Weale, A.: J. Chem. Phys. 129, 054901 (2008). doi:10.1063/1.2939242
Hoepfner, M.P., Fávero, C.V.B., Haji-Akbari, N., Fogler, H.S.: Langmuir 29(28), 8799 (2013). doi:10.1021/la401406k
Putnam, C.D., Hammel, M., Hura, G.L., Tainer, J.A.: Q. Rev. Biophys. 40(3), 191 (2007). doi:10.1017/S0033583507004635
Goldsmith, E., Sprang, S., Fletterick, R.: J. Mol. Biol. 156(2), 411 (1982)
Filippov, S.K., Sedlacek, O., Bogomolova, A., Vetrik, M., Jirak, D., Kovar, J., Kucka, J., Bals, S., Turner, S., Stepanek, P., Hruby, M.: Macromol. Biosci. 12(12), 1731 (2012). doi:10.1002/mabi.201200294
Konkolewicz, D., Perrier, S., Stapleton, D., Gray-Weale, A.: J. Polym. Sci. B Polym. Phys. 49, 1525 (2011). doi:10.1002/polb.22340
Berg, J., Tymoczko, J., Stryer, L.: In: Biochemistry. 5th edn. chap. 12. W.H. Freeman, New York (2002)
Gerich, J.E.: Bailliere Clin. Endocrinol. Metab. 7(3), 551 (1993)
Leney, S.E., Tavaré, J.M.: J. Endocrinol. 203(1), 1 (2009). doi:10.1677/JOE-09-0037
Kahn, B.B., Flier, J.S.: J. Clin. Invest. 106(4), 473 (2000)
Saltiel, A.R., Kahn, C.R.: Nature 414, 799 (2001)
Postic, C., Dentin, R., Girard, J.: Diabetes and Metabolism 30(5), 398 (2004)
Hers, H.G., Barsy, T.D., Lederer, B., Hue, L., Van Hoof, F.: Birth Defects Original Article Series 12(6), 145 (1974)
Nitschke, F., Wang, P., Schmieder, P., Girard, J.M., Awrey, D.E., Wang, T., Israelian, J., Zhao, X., Turnbull, J., Heydenreich, M., Kleinpeter, E., Steup, M., Minassian, B.A.: Cell Metab. 17(5), 756 (2013). doi:10.1016/j.cmet.2013.04.006
Roach, P.J.: Mol. Asp. Med. (2015). doi:10.1016/j.mam.2015.08.003
Jiang, G., Zhang, B.B.: American Journal of Endocrinology and Metabolism 284(4), 671 (2003). doi:10.1152/ajpendo.00492.2002
Cryer, P.E.: N. Engl. J. Med. 369(4), 362 (2013). doi:10.1056/NEJMra1215228
Zammitt, N.N., Frier, B.M.: Diabetes Care 88(4), 1107 (2005). doi:10.1016/j.mcna.2004.04.003
Krssak, M., Brehm, A., Bernroider, E., Anderwald, C., Nowotny, P., Man, C.D., Cobelli, C., Cline, G.W., Shulman, G.I., Waldha, W., Roden, M.: Diabetes 53, 3048 (2004)
Mayes, P.A., Bender, D.A.: . In: Harper’s Biochemistry. 23rd edn. chap. 18, pp. 145–152. Appleton & Lange, Norwalk (1993)
Sullivan, M.A., Li, J., Li, C., Vilaplana, F., Stapleton, D., Gray-Weale, A.A., Bowen, S., Zheng, L., Gilbert, R.G.: Biomacromolecules 12(6), 1983 (2011). doi:10.1021/bm2006054
Zeng, X.Y., Wang, Y.P., Cantley, J., Iseli, T.J., Molero, J.C., Hegarty, B.D., Kraegen, E.W., Ye, Y., Ye, J.M.: PLoS One 7(7), e42115 (2012). doi:10.1371/journal.pone.0042115
Kaszuba, M., McKnight, D., Connah, M.T., McNeil-Watson, F.K., Nobbmann, U.: J. Nanopart. Res. 10(5), 823 (2007). doi:10.1007/s11051-007-9317-4
Deng, B., Sullivan, M.A., Li, J., Tan, X., Zhu, C., Schulz, B.L., Gilbert, R.G.: Glycoconjugate J. 32, 113 (2015). doi:10.1007/s10719-015-9578-6
Arjmandi, N., Van Roy, W., Lagae, L., Borghs, G.: Anal. Chem. 84(20), 8490 (2012). doi:10.1021/ac300705z
Tagliabracci, V.S., Heiss, C., Karthik, C., Contreras, C.J., Glushka, J., Ishihara, M., Azadi, P., Hurley, T.D., Depaoli-Roach, A.A., Roach, P.J.: Cell Metab. 13(3), 274 (2011). doi:10.1016/j.cmet.2011.01.017
Magnusson, I., Rothman, D.L., Katz, L.D., Shulman, R.G., Shulman, G.I.: J. Clin. Invest. 90(4), 1323 (1992). doi:10.1172/JCI115997
Clore, J.N., Blackard, W.G.: Diabetes 43, 256 (1994)
Rathgeber, S., Monkenbusch, M., Kreitschmann, M., Urban, V., Brulet, A.: J. Chem. Phys. 117 (8), 4047 (2002). doi:10.1063/1.1493771
Franke, D., Svergun, D.: J. Appl. Crystallogr. 42, 342 (2009)
Caldwell, R., Matheson, N.: Carbohydr. Polym. 54(2), 201 (2003). doi:10.1016/S0144-8617(03)00161-9
Matheson, N.K., Caldwell, R.A.: Carbohydr. Polym. 40, 191 (1999)
Bale, H.D., Schmidt, P.W.: Phys. Rev. Lett. 53(6), 596 (1984)
Martin, J.E., Hurd, A.J.: J. Appl. Crystallogr. 20(2), 61 (1987). doi:10.1107/S0021889887087107
Rieker, T.P., Hindermann-Bischoff, M., Ehrburger-Dolle, F.: Langmuir 16(13), 5588 (2000). doi:10.1021/la991636a
Reich, M.H., Snook, I.K., Wagenfeld, H.K.: Fuel 71, 669 (1992)
Svergun, D.I.: Biophys. J. 76, 2879 (1999). doi:10.1016/S0006-3495(99)77443-6
Acknowledgments
The assistance from Dr. Nigel Kirby and Nathan Cowieson at the SAXS beamline is gratefully acknowledged. QAB and XYZ would like to thank the Australian government for APA scholarships, and the Univeristy of Melbourne for receipt of the Albert Shimmins award and the Norma Hilda Schuster scholarship (QAB). This study was partially supported by funding from the Melbourne Materials Institute (QAB, AGW), the Australian Synchrotron (beamline time) (QAB, AGW), the Victorian Life Sciences Computation Initiative (QAB, AGW, Grant No. VRO252), and the Australian Research Council for grant ARCDP110102396 (JMY).
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Besford, Q.A., Zeng, XY., Ye, JM. et al. Liver glycogen in type 2 diabetic mice is randomly branched as enlarged aggregates with blunted glucose release. Glycoconj J 33, 41–51 (2016). https://doi.org/10.1007/s10719-015-9631-5
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DOI: https://doi.org/10.1007/s10719-015-9631-5