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International Journal of Endocrinology
Volume 2017 (2017), Article ID 7861236, 14 pages
https://doi.org/10.1155/2017/7861236
Research Article

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain

1Department of Veterinary Disease Biology, Section for Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
2Department of Toxicology, Safety Pharm and Pathology, Novo Nordisk A/S, Maaloev, Denmark
3Division of Toxicology, Envigo, Eye, Suffolk, UK
4Department of Development DMPK, Novo Nordisk A/S, Maaloev, Denmark
5Department of Development Bioanalysis, Novo Nordisk A/S, Maaloev, Denmark

Correspondence should be addressed to Vivi F. H. Jensen; moc.ksidronovon@jhfv

Received 30 June 2016; Revised 19 December 2016; Accepted 26 December 2016; Published 21 March 2017

Academic Editor: Darío Acuña-Castroviejo

Copyright © 2017 Vivi F. H. Jensen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Group, T.D.R, “Epidemiology of severe hypoglycemia in the diabetes control and complications trial,” The American Journal of Medicine, vol. 90, no. 4, pp. 450–459, 1991. View at Publisher · View at Google Scholar · View at Scopus
  2. Group, T.D.R, “The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus,” The New England Journal of Medicine, vol. 329, no. 14, pp. 977–986, 1993. View at Publisher · View at Google Scholar
  3. C. D. Miller, L. S. Phillips, D. C. Ziemer, D. L. Gallina, C. B. Cook, and I. M. El-Kebbi, “Hypoglycemia in patients with type 2 diabetes mellitus,” Archives of Internal Medicine, vol. 161, no. 13, pp. 1653–1659, 2001. View at Publisher · View at Google Scholar
  4. B. Widom and D. C. Simonson, “Intermittent hypoglycemia impairs glucose counterregulation,” Diabetes, vol. 41, no. 12, pp. 1597–1602, 1992. View at Publisher · View at Google Scholar
  5. P. E. Cryer, “Iatrogenic hypoglycemia as a cause of hypoglycemia-associated autonomic failure in IDDM. A vicious cycle,” Diabetes, vol. 41, no. 3, pp. 255–260, 1992. View at Publisher · View at Google Scholar
  6. P. E. Cryer, “Mechanisms of hypoglycemia-associated autonomic failure in diabetes,” The New England Journal of Medicine, vol. 369, no. 4, pp. 362–372, 2013. View at Publisher · View at Google Scholar · View at Scopus
  7. V. F. Jensen, I. B. Bogh, and J. Lykkesfeldt, “Effect of insulin-induced hypoglycaemia on the central nervous system: evidence from experimental studies,” Journal of Neuroendocrinology, vol. 26, no. 3, pp. 123–150, 2014. View at Publisher · View at Google Scholar · View at Scopus
  8. R. N. Auer, Y. Olsson, and B. K. Siesjo, “Hypoglycemic brain injury in the rat. Correlation of density of brain damage with the EEG isoelectric time: a quantitative study,” Diabetes, vol. 33, no. 11, pp. 1090–1098, 1984. View at Publisher · View at Google Scholar
  9. R. N. Auer, T. Wieloch, Y. Olsson, and B. K. Siesjö, “The distribution of hypoglycemic brain damage,” Acta Neuropathologica, vol. 64, no. 3, pp. 177–191, 1984. View at Publisher · View at Google Scholar · View at Scopus
  10. G. Feise, K. Kogure, K. R. Busto, P. Scheinberg, and O. M. Reinmuth, “Effect of insulin hypoglycemia upon cerebral energy metabolism and EEG activity in the rat,” Brain Research, vol. 126, no. 2, pp. 263–280, 1977. View at Publisher · View at Google Scholar · View at Scopus
  11. D. H. Lee, M. Y. Chung, J. U. Lee, D. G. Kang, and Y. W. Paek, “Changes of glucose transporters in the cerebral adaptation to hypoglycemia,” Diabetes Research and Clinical Practice, vol. 47, no. 1, pp. 15–23, 2000. View at Publisher · View at Google Scholar · View at Scopus
  12. A. K. Kumagai, Y. S. Kang, R. J. Boado, and W. M. Pardridge, “Upregulation of blood-brain barrier GLUT1 glucose transporter protein and mRNA in experimental chronic hypoglycemia,” Diabetes, vol. 44, no. 12, pp. 1399–1404, 1995. View at Publisher · View at Google Scholar
  13. R. Duelli, R. Staudt, L. Duembgen, and W. Kuschinsky, “Increase in glucose transporter densities of Glut3 and decrease of glucose utilization in rat brain after one week of hypoglycemia,” Brain Research, vol. 831, no. 1-2, pp. 254–262, 1999. View at Publisher · View at Google Scholar · View at Scopus
  14. Y. Uehara, V. Nipper, and A. L. McCall, “Chronic insulin hypoglycemia induces GLUT-3 protein in rat brain neurons,” The American Journal of Physiology, vol. 272, no. 4 Pt 1, pp. E716–E719, 1997. View at Google Scholar
  15. J. W. Mastaitis, E. Wurmbach, H. Cheng, S. C. Sealfon, and C. V. Mobbs, “Acute induction of gene expression in brain and liver by insulin-induced hypoglycemia,” Diabetes, vol. 54, no. 4, pp. 952–958, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. S. W. Suh, A. M. Hamby, and R. A. Swanson, “Hypoglycemia, brain energetics, and hypoglycemic neuronal death,” Glia, vol. 55, no. 12, pp. 1280–1286, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. P. Singh, A. Jain, and G. Kaur, “Impact of hypoglycemia and diabetes on CNS: correlation of mitochondrial oxidative stress with DNA damage,” Molecular and Cellular Biochemistry, vol. 260, no. 1–2, pp. 153–159, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Patockova, P. Marhol, E. Tůmová et al., “Oxidative stress in the brain tissue of laboratory mice with acute post insulin hypoglycemia,” Physiological Research, vol. 52, no. 1, pp. 131–135, 2003. View at Google Scholar
  19. M. L. Haces, T. Montiel, and L. Massieu, “Selective vulnerability of brain regions to oxidative stress in a non-coma model of insulin-induced hypoglycemia,” Neuroscience, vol. 165, no. 1, pp. 28–38, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. T. M. Dawson, V. L. Dawson, and S. H. Snyder, “A novel neuronal messenger molecule in brain: the free radical, nitric oxide,” Annals of Neurology, vol. 32, no. 3, pp. 297–311, 1992. View at Publisher · View at Google Scholar
  21. V. F. H. Jensen, A. M. Mølck, A. Heydenreich et al., “Histopathological nerve and skeletal muscle changes in rats subjected to persistent insulin-induced hypoglycemia,” Journal of Toxicologic Pathology, vol. 29, no. 1, pp. 17–30, 2016. View at Publisher · View at Google Scholar · View at Scopus
  22. EU, Directive 2004/10/EC of the European Parliament and of the Council of 11 February 2004 on the Harmonisation of Laws, Regulations and Administrative Provisions Relating to the Application of the Principles of Good Laboratory Practice and the Verification of their Applications for Tests on Chemical Substances, 2004.
  23. OECD, OECD Principles on Good Laboratory Practice, 1998.
  24. UK, G, The Good Laboratory Practice (Codification Amendments Etc.) Regulations 2004, in SI 2004/944, 2004.
  25. Y. Gomez-Perez, E. Amengual-Cladera, A. Català-Niell et al., “Gender dimorphism in high-fat-diet-induced insulin resistance in skeletal muscle of aged rats,” Cellular Physiology and Biochemistry, vol. 22, no. 5-6, pp. 539–548, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. Y. Gomez-Perez, M. Gianotti, A. M. Proenza, and I. Lladó, “Age-related decline of skeletal muscle insulin sensitivity in rats: effect of sex and muscle type,” Rejuvenation Research, vol. 14, no. 2, pp. 153–161, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. C. Gustavsson, K. Yassin, E. Wahlström et al., “Sex-different hepaticglycogen content and glucose output in rats,” BMC Biochemistry, vol. 11, 38 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Plum, H. Agersø, and L. Andersen, “Pharmacokinetics of the rapid-acting insulin analog, insulin aspart, in rats, dogs, and pigs, and pharmacodynamics of insulin aspart in pigs,” Drug Metabolism and Disposition, vol. 28, no. 2, pp. 155–160, 2000. View at Google Scholar
  29. J. Lykkesfeldt, “Determination of malondialdehyde as dithiobarbituric acid adduct in biological samples by HPLC with fluorescence detection: comparison with ultraviolet-visible spectrophotometry,” Clinical Chemistry, vol. 47, no. 9, pp. 1725–1727, 2001. View at Google Scholar
  30. Z. Wang, Y. Yang, X. Xiang, Y. Zhu, J. Men, and M. He, “Estimation of the normal range of blood glucose in rats,” Wei Sheng Yan Jiu, vol. 39, no. 2, pp. 133–137, 2010, 142 View at Google Scholar
  31. S. F. De Boer, S. J. Koopmans, J. L. Slangen, and J. Van der Gugten, “Effects of fasting on plasma catecholamine, corticosterone and glucose concentrations under basal and stress conditions in individual rats,” Physiology & Behavior, vol. 45, no. 5, pp. 989–994, 1989. View at Publisher · View at Google Scholar · View at Scopus
  32. M. H. Nowland, K. M. Hugunin, and K. L. Rogers, “Effects of short-term fasting in male Sprague-Dawley rats,” Comparative Medicine, vol. 61, no. 2, pp. 138–144, 2011. View at Google Scholar
  33. J. Mayer and M. W. Bates, “Blood glucose and food intake in normal and hypophysectomized, alloxan-treated rats,” The American Journal of Physiology, vol. 168, no. 3, pp. 812–819, 1952. View at Google Scholar
  34. K. K. May and J. R. Beaton, “Hyperphagia in the insulin-treated rat,” Proceedings of the Society for Experimental Biology and Medicine, vol. 127, pp. 1201–1204, 1968. View at Publisher · View at Google Scholar · View at Scopus
  35. Y. T. Kruszynska, L. Villa-Komaroff, and P. A. Halban, “Islet B-cell dysfunction and the time course of recovery following chronic overinsulinisation of normal rats,” Diabetologia, vol. 31, no. 8, pp. 621–626, 1988. View at Publisher · View at Google Scholar · View at Scopus
  36. G. Paz-Filho, C. Mastronardi, M. L. Wong, and J. Licinio, “Leptin therapy, insulin sensitivity, and glucose homeostasis,” Indian Journal of Endocrinology and Metabolism, vol. 16, Supplement 3, pp. S549–S555, 2012. View at Publisher · View at Google Scholar
  37. I. A. Simpson, N. M. Appel, M. Hokari et al., “Blood-brain barrier glucose transporter: effects of hypo- and hyperglycemia revisited,” Journal of Neurochemistry, vol. 72, no. 1, pp. 238–247, 1999. View at Publisher · View at Google Scholar · View at Scopus
  38. R. Poppe, U. Karbach, S. Gambaryan et al., “Expression of the Na+-D-glucose cotransporter SGLT1 in neurons,” Journal of Neurochemistry, vol. 69, no. 1, pp. 84–94, 1997. View at Publisher · View at Google Scholar
  39. E. M. Wright, “Renal Na(+)-glucose cotransporters,” American Journal of Physiology. Renal Physiology, vol. 280, no. 1, pp. F10–F18, 2001. View at Google Scholar
  40. E. Fuente-Martin, C. García-Cáceres, M. Granado et al., “Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes,” The Journal of Clinical Investigation, vol. 122, no. 11, pp. 3900–3913, 2012. View at Publisher · View at Google Scholar · View at Scopus
  41. M. C. Lacroix, M. Caillol, D. Durieux et al., “Long-lasting metabolic imbalance related to obesity alters olfactory tissue homeostasis and impairs olfactory-driven behaviors,” Chemical Senses, vol. 40, no. 8, pp. 537–556, 2015. View at Publisher · View at Google Scholar · View at Scopus
  42. Y. Benomar, N. Naour, A. Aubourg et al., “Insulin and leptin induce Glut4 plasma membrane translocation and glucose uptake in a human neuronal cell line by a phosphatidylinositol 3-kinase-dependent mechanism,” Endocrinology, vol. 147, no. 5, pp. 2550–2556, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Amitani, A. Asakawa, H. Amitani, and A. Inui, “The role of leptin in the control of insulin-glucose axis,” Frontiers in Neuroscience, vol. 7, 51 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. H. Kipp, S. Khoursandi, D. Scharlau, and R. K. Kinne, “More than apical: distribution of SGLT1 in Caco-2 cells,” American Journal of Physiology. Cell Physiology, vol. 285, no. 4, pp. C737–C749, 2003. View at Publisher · View at Google Scholar
  45. A. Ikari, M. Nakano, K. Kawano, and Y. Suketa, “Up-regulation of sodium-dependent glucose transporter by interaction with heat shock protein 70,” The Journal of Biological Chemistry, vol. 277, no. 36, pp. 33338–33343, 2002. View at Publisher · View at Google Scholar · View at Scopus
  46. O. Delezay, S. Baghdiguian, and J. Fantini, “The development of Na(+)-dependent glucose transport during differentiation of an intestinal epithelial cell clone is regulated by protein kinase C,” The Journal of Biological Chemistry, vol. 270, no. 21, pp. 12536–12541, 1995. View at Publisher · View at Google Scholar · View at Scopus
  47. A. Moran, R. J. Turner, and J. S. Handler, “Regulation of sodium-coupled glucose transport by glucose in a cultured epithelium,” The Journal of Biological Chemistry, vol. 258, no. 24, pp. 15087–15090, 1983. View at Google Scholar
  48. A. Moran, R. J. Turner, and J. S. Handler, “Hexose regulation of sodium-hexose transport in LLC-PK1 epithelia: the nature of the signal,” The Journal of Membrane Biology, vol. 82, no. 1, pp. 59–65, 1984. View at Publisher · View at Google Scholar · View at Scopus
  49. S. Arthur, S. Coon, R. Kekuda, and U. Sundaram, “Regulation of sodium glucose co-transporter SGLT1 through altered glycosylation in the intestinal epithelial cells,” Biochimica et Biophysica Acta, vol. 1838, no. 5, pp. 1208–1214, 2014. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Coon, J. Kim, G. Shao, and U. Sundaram, “Na-glucose and Na-neutral amino acid cotransport are uniquely regulated by constitutive nitric oxide in rabbit small intestinal villus cells,” American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 289, no. 6, pp. G1030–G1035, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Ducroc, S. Guilmeau, K. Akasbi, H. Devaud, M. Buyse, and A. Bado, “Luminal leptin induces rapid inhibition of active intestinal absorption of glucose mediated by sodium-glucose cotransporter 1,” Diabetes, vol. 54, no. 2, pp. 348–354, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. J. A. Dominguez Rieg, V. R. Chirasani, H. Koepsell, S. Senapati, S. K. Mahata, and T. Rieg, “Regulation of intestinal SGLT1 by catestatin in hyperleptinemic type 2 diabetic mice,” Laboratory Investigation, vol. 96, no. 1, pp. 98–111, 2016. View at Publisher · View at Google Scholar · View at Scopus
  53. Y. Macotela, J. Boucher, T. T. Tran, and C. R. Kahn, “Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism,” Diabetes, vol. 58, no. 4, pp. 803–812, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. C. M. Cheng, M. Cohen, J. Wang, and C. A. Bondy, “Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex,” The FASEB Journal, vol. 15, no. 6, pp. 907–915, 2001. View at Publisher · View at Google Scholar · View at Scopus
  55. K. Pierre and L. Pellerin, “Monocarboxylate transporters in the central nervous system: distribution, regulation and function,” Journal of Neurochemistry, vol. 94, no. 1, pp. 1–14, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. N. Blume, J. Skouv, L. I. Larsson, J. J. Holst, and O. D. Madsen, “Potent inhibitory effects of transplantable rat glucagonomas and insulinomas on the respective endogenous islet cells are associated with pancreatic apoptosis,” The Journal of Clinical Investigation, vol. 96, no. 5, pp. 2227–2235, 1995. View at Publisher · View at Google Scholar
  57. B. J. Frankel, F. G. Schmid, and G. M. Grodsky, “Effect of continuous insulin infusion with an implantable seven-day minipump in the diabetic Chinese hamster,” Endocrinology, vol. 104, no. 5, pp. 1532–1539, 1979. View at Publisher · View at Google Scholar
  58. T. R. Koiter, S. Wijkstra, C. J. van Der Schaaf-Verdonk, H. Moes, and G. A. Schuiling, “Pancreatic beta-cell function and islet-cell proliferation: effect of hyperinsulinaemia,” Physiology & Behavior, vol. 57, no. 4, pp. 717–721, 1995. View at Publisher · View at Google Scholar · View at Scopus
  59. P. Montuschi, P. J. Barnes, and L. J. Roberts 2nd, “Isoprostanes: markers and mediators of oxidative stress,” The FASEB Journal, vol. 18, no. 15, pp. 1791–1800, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Ayala, M. F. Munoz, and S. Arguelles, “Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal,” Oxidative Medicine and Cellular Longevity, vol. 2014, Article ID 360438, 31 pages, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. S. Cardoso, R. X. Santos, S. C. Correia et al., “Insulin-induced recurrent hypoglycemia exacerbates diabetic brain mitochondrial dysfunction and oxidative imbalance,” Neurobiology of Disease, vol. 49, pp. 1–12, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. V. Katalinic, D. Modun, I. Music, and M. Boban, “Gender differences in antioxidant capacity of rat tissues determined by 2,2′-azinobis (3-ethylbenzothiazoline 6-sulfonate; ABTS) and ferric reducing antioxidant power (FRAP) assays,” Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, vol. 140, no. 1, pp. 47–52, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. Y. Ihara, S. Toyokuni, K. Uchida et al., “Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes,” Diabetes, vol. 48, no. 4, pp. 927–932, 1999. View at Publisher · View at Google Scholar
  64. M. Otsyula, M. S. King, T. G. Ketcham, R. A. Sanders, and J. B. Watkins 3rd, “Oxidative stress in rats after 60 days of hypergalactosemia or hyperglycemia,” International Journal of Toxicology, vol. 22, no. 6, pp. 423–427, 2003. View at Publisher · View at Google Scholar