Please cite this article in press as: Q.A. Besford, et al., Int. J. Biol. Macromol. (2012), http://dx.doi.org/10.1016/j.ijbiomac.2012.06.037 ARTICLE IN PRESS G Model BIOMAC 3303 1–5 International Journal of Biological Macromolecules xxx (2012) xxx–xxx Contents lists available at SciVerse ScienceDirect International Journal of Biological Macromolecules jo u r n al hom epa ge: ww w.elsevier.com/locate/ijbiomac Short communication 1 The structure of cardiac glycogen in healthy mice 2 Quinn A. Besford a , Mitchell A. Sullivan b , Ling Zheng c , Robert G. Gilbert b , Q1 David Stapleton d , Angus Gray-Weale a,∗ 3 4 a School of Chemistry, University of Melbourne, Victoria 3010, Australia 5 b Centre for Nutrition and Food Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia 6 c College of Life Sciences, Wuhan University, Wuhan 430072, China 7 d Department of Physiology, University of Melbourne, Victoria 3010, Australia 8 9 a r t i c l e i n f o 10 11 Article history: 12 Received 16 February 2012 13 Received in revised form 6 May 2012 14 Accepted 26 June 2012 15 Available online xxx 16 Keywords: 17 Glycogen 18 Transmission electron microscopy 19 Dynamic light scattering 20 a b s t r a c t Transmission electron micrographs of glycogen extracted from healthy mouse hearts reveal aggregate structures around 133 nm in diameter. These structures are similar to, but on average somewhat smaller than, the -particles of glycogen found in mammalian liver. Like the larger liver glycogens, these new particles in cardiac tissue appear to be aggregates of -particles. Free -particles are also present in liver, and are the only type of particle seen in skeletal muscle. They have diameters from 20 to 50 nm. We discuss the number distributions of glycogen particle diameters and the implications for the structure–function relationship of glycogens in these tissues. We point out the possible implications for the study of glycogen storage diseases, and of non-insulin dependent diabetes mellitus. © 2012 Elsevier B.V. All rights reserved. 1. Introduction 21 Glycogen is a highly branched polysaccharide, used by mammals 22 in their livers to control blood glucose [1], and in their muscles as 23 a ready, local fuel store [2]. The different purposes of glycogen in 24 these tissues reflect their different structures: liver cells contain - 25 particles, aggregates of -particles, on average about 150 nm, and 26 up to about 300 nm, in diameter [3,4]; other cells, skeletal muscle 27 for example, are known to contain -particles from 20 to 50 nm 28 in diameter [2]. Until now, it has seemed that the distribution of 29 sizes in healthy mammal cells follows this simple pattern. Storing 30 glucose in polymeric form reduces the osmotic stress on the cell 31 [5], but glycogen is not merely a passive fuel store. It participates 32 in the regulation of a cell’s energy supply. For example, different 33 sized particles of glycogen are made and broken down at different 34 rates [6], and so the distribution of particle sizes controls glyco- 35 gen’s response time to glucose concentrations, and its ability to 36 buffer glucose concentrations. Further, high muscle glycogen con- 37 tent is correlated with reduced activation of AMP-activated protein 38 kinase (AMPK) by the AMP mimic, AICA riboside in perfused rat 39 muscle [7], and by exercise in human muscle [8]. It has also been 40 argued that glycogen is an anchor point for other macromolecules 41 [9], which is consistent with the suggestion that glycogen particles 42 are localised to different parts of the cell, and provide “different 43 ∗ Corresponding author. E-mail addresses: dis@unimelb.edu.au (D. Stapleton), angusg@unimelb.edu.au (A. Gray-Weale). metabolic pools” [2]. With the possible exception of AMPK activa- 44 tion, for all of these roles glycogen’s particle size is essential to its 45 function, and this reinforces the suggestion that the different role 46 of glycogen in liver cells dictates its distinctive aggregate -particle 47 structure. Measuring the structure of glycogen, and in particular its 48 distribution of particle sizes, is a route to better understanding of 49 its various roles. Roach has pointed out that glycogen exists as a 50 continuous distribution of species of different sizes, with the exact 51 distribution depending on both the synthetic and degradative arms 52 of glycogen metabolism [10]. 53 Though the heart obtains 60–90% of its energy from fatty acids 54 [11], some comes from carbohydrate [12], with the heart muscle 55 cells containing about 2% glycogen by volume [9,13]. Pederson et al. 56 studied mice with the GYS1 gene that encodes an isoform of glyco- 57 gen synthase disrupted, and found that most GYS1-null animals 58 died after birth [13]. This work shows that the ability to synthe- 59 sise glycogen is critical to heart development. The stress responses 60 of heart muscle glycogen have particular features not reported 61 in other tissues. Fasting for 48 h decreases both skeletal muscle 62 and liver glycogen, but increases heart muscle glycogen levels 63 [14,15]. An early report classes kidney, heart, and stomach glyco- 64 gens together as they are not reduced after a 48 h fast [16]. Luptak 65 et al. showed that a lifelong increase in a mouse heart’s glucose 66 uptake, induced by overexpression of the GLUT1 glucose trans- 67 porter in a mouse heart, improves resistance to ischemic injury 68 [17]. Tian and Abel showed that mouse hearts deficient in GLUT4, 69 normally the more abundant glucose transporter, are more sus- 70 ceptible to ischemia, and that glycogen stores in fed mice partly 71 compensate for this effect [18]. In an earlier review, Taegtmeyer 72 0141-8130/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijbiomac.2012.06.037