Cited by 389Regulation of Appetite and ObesityNeuropeptides and Animal PhysiologyHypothalamic control of reproductive hormones

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Effect of Intracerebroventricular Insulin Infusion on Diabetic Hyperphagia and Hypothalamic Neuropeptide Gene Expression

Sipols, Alfred J, Baskin, Denis G, Schwartz, Michael W·1995·Diabetes

DOI 10.2337/diab.44.2.147

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Abstract

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.

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Authors: Sipols, A. J., Baskin, D. G., & Schwartz, M. W.
Affiliations: University of Washington (US)
ORCID: Baskin, Denis G
Schwartz, Michael W
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1995-02-01
Volume: 44
Issue: 2
Pages: 147-151
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diab.44.2.147
OpenAlex: W2099542131
Cited by: 389
References: 0
Citations by year: 2026: 1 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 14 · 2017: 11 · 2016: 14 · 2015: 6 · 2014: 13 · 2013: 16 · 2012: 15
FWCI: 4.57
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs
National Institutes of Health (2r01dk012829-36)
Diabetes Research Center, University of Washington
National Institute of Diabetes and Digestive and Kidney Diseases (DK 12829, DK17844, DK-17047, P30DK017047)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords: neuropeptide Y, cholecystokinin, corticotropin-releasing factor, hypothalamic arcuate nucleus, hypothalamic paraventricular nucleus, dietary intake, streptozotocin-induced diabetes, neuropeptide gene expression, weight loss
MeSH terms: Animals, Base Sequence, Brain, Cholecystokinin, Corticotropin-Releasing Hormone, Diabetes Mellitus, Experimental, Hyperphagia, Hypothalamus, Insulin, Male, Molecular Sequence Data, Neuropeptide Y, Neuropeptides, RNA, Messenger, Gene Expression, Rats, Wistar, In Situ Hybridization, Rats

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Effect of Intracerebroventricular Insulin Infusion on Diabetic Hyperphagia and Hypothalamic Neuropeptide Gene Expression

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