Effect of Intracerebroventricular Insulin Infusion on Diabetic Hyperphagia and Hypothalamic Neuropeptide Gene Expression
| Autor: | Alfred J. Sipols, Michael W. Schwartz, Denis G. Baskin |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Corticotropin-Releasing Hormone Endocrinology Diabetes and Metabolism medicine.medical_treatment media_common.quotation_subject Molecular Sequence Data Hypothalamus Gene Expression Neuropeptide Hyperphagia Biology Diabetes Mellitus Experimental Corticotropin-releasing hormone Diabetes mellitus Internal medicine Internal Medicine medicine Animals Insulin Neuropeptide Y RNA Messenger Rats Wistar In Situ Hybridization Pancreatic hormone media_common Base Sequence Neuropeptides digestive oral and skin physiology Brain Appetite medicine.disease Neuropeptide Y receptor Rats Endocrinology Cholecystokinin hormones hormone substitutes and hormone antagonists |
| Zdroj: | Diabetes. 44:147-151 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diab.44.2.147 |
| Popis: | To test the hypothesis that diabetic hyperphagia results from insulin deficiency in the brain, diabetic rats (streptozotocin-induced) were given an intracerebroventricular (ICV) infusion of saline or insulin (at a dose that did not affect plasma glucose levels) for 6 days. Food and water intake were significantly increased in diabetic rats, but only food intake was affected by ICV insulin. Diabetic hyperphagia was reduced 58% by ICV insulin compared with ICV saline (P < 0.05) and was accompanied by a 69% increase in diabetes-induced weight loss (P < 0.05). To evaluate whether central nervous system (CNS) insulin deficiency affects expression of neuropeptides involved in food intake, in situ hybridization was done for neuropeptide Y (NPY), which stimulates feeding, in the hypothalamic arcuate nucleus and for cholecystokinin (CCK) and corticotropin-releasing hormone (CRH), which inhibit feeding, in the hypothalamic paraventricular nucleus. In diabetic rats, NPY mRNA hybridization increased 280% (P < 0.05), an effect reduced 40% by ICV insulin (P < 0.05). CCK mRNA hybridization increased 50% in diabetic rats (P < 0.05), a response reduced slightly by ICV insulin (P < 0.05), whereas CRH mRNA hybridization decreased 33% in diabetic rats (P < 0.05) and was unchanged by ICV insulin. The results demonstrate that CNS infusion of insulin to diabetic rats reduces both hyperphagia and overexpression of hypothalamic NPY mRNA. This observation supports the hypothesis that a deficiency of insulin in the brain is an important cause of diabetic hyperphagia and that increased hypothalamic NPY gene expression contributes to this phenomenon. |
| Databáze: | OpenAIRE |
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