Advertisement

The Journal of Physiological Sciences

, Volume 68, Issue 1, pp 69–75 | Cite as

Differential effects of type 2 diabetes on brain glycometabolism in rats: focus on glycogen and monocarboxylate transporter 2

  • Takeru Shima
  • Subrina Jesmin
  • Takashi Matsui
  • Mariko Soya
  • Hideaki SoyaEmail author
Original Paper

Abstract

Astrocyte-neuron lactate shuttle (ANLS) is a pathway that supplies glycogen-derived lactate to active neurons via monocarboxylate transporter 2 (MCT2), and is important for maintaining brain functions. Our study revealed alterations of ANLS with hippocampal hyper-glycogen levels and downregulated MCT2 protein levels underlying hippocampal dysfunctions as a complication in type 2 diabetic (T2DM) animals. Since T2DM rats exhibit brain dysfunctions involving several brain regions, we examined whether there might also be T2DM effects on ANLS’s disturbances in other brain loci. OLETF rats exhibited significantly higher glycogen levels in the hippocampus, hypothalamus, and cerebral cortex than did LETO rats. MCT2 protein levels in OLETF rats decreased significantly in the hippocampus and hypothalamus compared to their controls, but a significant correlation with glycogen levels was only observed in the hippocampus. This suggests that the hippocampus may be more vulnerable to T2DM compared to other brain regions in the context of ANLS disruption.

Keywords

Astrocyte-neuron lactate shuttle Brain glycogen Hippocampus Monocarboxylate transporter Type 2 diabetes mellitus 

Notes

Acknowledgements

The authors are grateful to Randeep Rakwal, Yu-Fan Liu, Naoki Omori, Katsuhito Saito (University of Tsukuba, Japan) for technical support and discussion, and to Melissa Noguchi (ELCS English Language Consultation, Japan) for help with the manuscript. This study was funded by the “Global Initiative for Sports Neuroscience (GISN): For Development of Exercise Prescription Enhancing Cognitive Functions,” by special funds for Education and Research of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) granted to the “Body and Mind Integrated Sports Sciences (BAMIS) Project” and to the “Human High Performance (HHP) Research Project,” and by the Japan Society for the Promotion of Science (Grants-in-aid for Scientific Research A, No. 15H01828; Challenging Exploratory Research, No. 23650384).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12576_2016_508_MOESM1_ESM.docx (1.2 mb)
Supplementary material 1 (DOCX 1198 kb)

References

  1. 1.
    Tsacopoulos M, Magistretti PJ (1996) Metabolic coupling between glia and neurons. J Neurosci 16:877–885CrossRefGoogle Scholar
  2. 2.
    Benarroch EE (2010) Glycogen metabolism: metabolic coupling between astrocytes and neurons. Neurology 74:919–923CrossRefGoogle Scholar
  3. 3.
    Suzuki A, Stern SA, Bozdagi O et al (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144:810–823CrossRefGoogle Scholar
  4. 4.
    Tang F, Lane S, Korsak A et al (2014) Lactate-mediated glia-neuronal signalling in the mammalian brain. Nat Commun 5:3284CrossRefGoogle Scholar
  5. 5.
    Pierre K, Pellerin L (2005) Monocarboxylate transporters in the central nervous system: distribution, regulation and function. J Neurochem 94:1–14CrossRefGoogle Scholar
  6. 6.
    Pellerin L, Magistretti PJ (2012) Sweet sixteen for ANLS. J Cereb Blood Flow Metab 32:1152–1166CrossRefGoogle Scholar
  7. 7.
    Lu W, Huang J, Sun S et al (2015) Changes in lactate content and monocarboxylate transporter 2 expression in Aβ25–35-treated rat model of Alzheimer’s disease. Neurol Sci 36:871–876CrossRefGoogle Scholar
  8. 8.
    Shima T, Matsui T, Jesmin S, et al (2016) Moderate exercise ameliorates dysregulated hippocampal glycometabolism and memory function in a rat model of type 2 diabetes. Diabetologia. Springer-Verlag, Germany (in press) CrossRefGoogle Scholar
  9. 9.
    Hoshino D, Setogawa S, Kitaoka Y et al (2016) Exercise-induced expression of monocarboxylate transporter 2 in the cerebellum and its contribution to motor performance. Neurosci Lett 633:1–6CrossRefGoogle Scholar
  10. 10.
    Bhattacharjee M, Venugopal B, Wong KT et al (2006) Mitochondrial disorder, diabetes mellitus, and findings in three muscles, including the heart. Ultrastruct Pathol 30:481–487CrossRefGoogle Scholar
  11. 11.
    King BM (2006) The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav 87:221–244CrossRefGoogle Scholar
  12. 12.
    Elmquist JK, Elias CF, Saper CB (1999) From lesions to leptin: hypothalamic control of food intake and body weight. Neuron 22:221–232CrossRefGoogle Scholar
  13. 13.
    Parekh B (2009) Mechanisms of the blunting of the sympatho-adrenal response: a theory. Curr Diabet Rev 5:79–91CrossRefGoogle Scholar
  14. 14.
    van Eersel MEA, Joosten H, Gansevoort RT et al (2013) The interaction of age and type 2 diabetes on executive function and memory in persons aged 35 years or older. PLoS One 8:e82991CrossRefGoogle Scholar
  15. 15.
    Kong J, Shepel PN, Holden CP et al (2002) Brain glycogen decreases with increased periods of wakefulness: implications for homeostatic drive to sleep. J Neurosci 22:5581–5587CrossRefGoogle Scholar
  16. 16.
    Suge R, Shimazu T, Hasegawa H et al (2012) Cerebral antioxidant enzyme increase associated with learning deficit in type 2 diabetes rats. Brain Res 1481:97–106CrossRefGoogle Scholar
  17. 17.
    Kawano K, Hirashima T, Mori S et al (1992) Spontaneous long-term hyperglycemic rat with diabetic complications: Otsuka Long-Evans Tokushima Fatty (OLETF) strain. Diabetes 41:1422–1428CrossRefGoogle Scholar
  18. 18.
    Hirano M, Rakwal R, Shibato J et al (2006) New protein extraction/solubilization protocol for gel-based proteomics of rat (female) whole brain and brain regions. Mol Cells 22:119–125PubMedGoogle Scholar
  19. 19.
    Matsui T, Soya S, Kawanaka K, Soya H (2015) Brain glycogen decreases during intense exercise without hypoglycemia: the possible involvement of serotonin. Neurochem Res 40:1333–1340CrossRefGoogle Scholar
  20. 20.
    Passonneau JV, Lauderdale VR (1974) A comparison of three methods of glycogen measurement in tissues. Anal Biochem 60:405–412CrossRefGoogle Scholar
  21. 21.
    Lee MC, Okamoto M, Liu YF et al (2012) Voluntary resistance running with short distance enhances spatial memory related to hippocampal BDNF signaling. J Appl Physiol 113:1260–1266CrossRefGoogle Scholar
  22. 22.
    Shearer J, Ross KD, Hughey CC et al (2011) Exercise training does not correct abnormal cardiac glycogen accumulation in the db/db mouse model of type 2 diabetes. Am J Physiol Endocrinol Metab 301:E31–E39CrossRefGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan 2016

Authors and Affiliations

  • Takeru Shima
    • 1
  • Subrina Jesmin
    • 1
    • 2
  • Takashi Matsui
    • 1
    • 2
  • Mariko Soya
    • 1
  • Hideaki Soya
    • 1
    • 2
    Email author
  1. 1.Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport SciencesUniversity of TsukubaTsukubaJapan
  2. 2.Department of Sports Neuroscience, Advanced Research Initiative for Human High Performance (ARIHHP)University of TsukubaTsukubaJapan

Personalised recommendations