Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain
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 o...
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Wiley
2017-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2017/7861236 |
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| author | Vivi F. H. Jensen Anne-Marie Mølck Melissa Chapman Lene Alifrangis Lene Andersen Jens Lykkesfeldt Ingrid B. Bøgh |
| author_facet | Vivi F. H. Jensen Anne-Marie Mølck Melissa Chapman Lene Alifrangis Lene Andersen Jens Lykkesfeldt Ingrid B. Bøgh |
| author_sort | Vivi F. H. Jensen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e70575f29fa044dc8a5932cf5841bac9 |
| institution | OA Journals |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-e70575f29fa044dc8a5932cf5841bac92025-08-20T02:21:10ZengWileyInternational Journal of Endocrinology1687-83371687-83452017-01-01201710.1155/2017/78612367861236Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the BrainVivi F. H. Jensen0Anne-Marie Mølck1Melissa Chapman2Lene Alifrangis3Lene Andersen4Jens Lykkesfeldt5Ingrid B. Bøgh6Department of Veterinary Disease Biology, Section for Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Toxicology, Safety Pharm and Pathology, Novo Nordisk A/S, Maaloev, DenmarkDivision of Toxicology, Envigo, Eye, Suffolk, UKDepartment of Development DMPK, Novo Nordisk A/S, Maaloev, DenmarkDepartment of Development Bioanalysis, Novo Nordisk A/S, Maaloev, DenmarkDepartment of Veterinary Disease Biology, Section for Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Toxicology, Safety Pharm and Pathology, Novo Nordisk A/S, Maaloev, DenmarkThe 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.http://dx.doi.org/10.1155/2017/7861236 |
| spellingShingle | Vivi F. H. Jensen Anne-Marie Mølck Melissa Chapman Lene Alifrangis Lene Andersen Jens Lykkesfeldt Ingrid B. Bøgh Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain International Journal of Endocrinology |
| title | Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain |
| title_full | Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain |
| title_fullStr | Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain |
| title_full_unstemmed | Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain |
| title_short | Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain |
| title_sort | chronic hyperinsulinaemic hypoglycaemia in rats is accompanied by increased body weight hyperleptinaemia and decreased neuronal glucose transporter levels in the brain |
| url | http://dx.doi.org/10.1155/2017/7861236 |
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