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International Journal of Endocrinology
Volume 2017 (2017), Article ID 7861236, 14 pages
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

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.


The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30–50% (4–6 mM versus 7–9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.