The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Abstract
We investigated the role of hypothalamic insulin signaling in the regulation of energy balance and insulin action in rats through selective decreases in insulin receptor expression in discrete hypothalamic nuclei. We generated an antisense oligodeoxynucleotide directed against the insulin receptor precursor protein and administered this directly into the third cerebral ventricle. Immunostaining of rat brains after 7-day administration of the oligodeoxynucleotide showed a selective decrease of insulin receptor protein within cells in the medial portion of the arcuate nucleus (decreased by approximately 80% as compared to rats treated with a control oligodeoxynucleotide). Insulin receptors in other hypothalamic and extra-hypothalamic areas were not affected. This selective decrease in hypothalamic insulin receptor protein was accompanied by rapid onset of hyperphagia and increased fat mass. During insulin-clamp studies, physiological hyperinsulinemia decreased glucose production by 55% in rats treated with control oligodeoxynucleotides but by only 25% in rats treated with insulin receptor antisense oligodeoxynucleotides. Thus, insulin receptors in discrete areas of the hypothalamus have a physiological role in the control of food intake, fat mass and hepatic action of insulin.
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“either intrahypothalamic administration of antisense oligonucleotides to reduce insulin receptor signaling or local infusion of the PI3K inhibitor, LY294002, causes hepatic insulin resistance in rats (132).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [132]
In the citing paper
“suggesting a shared neuronal mechanism mediating effects of both hormones on glucose metabolism (34,35).”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [34]
In the citing paper
“hypothalamic effects of both insulin and leptin are dependent on neuronal phosphatidylinositol-3-OH kinase signaling”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [34]
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Papazoglou, I. (2013) · theses.fr (ABES) · doi:10.70675/06d278b5zf0a0z456dz9c4cz9dc680b45fd3 · Cited by 1
Rouquet, T. (2015) · theses.fr (ABES) · doi:10.70675/680971a6z149ez4296z9c76z5ee9dfd53ce5
Galmiche, M. C. (2019) · theses.fr (ABES) · doi:10.70675/86478abdzfb8bz4442z8e08z65e991beb2b0
Triglyceride-sensing in the mesocorticolimbic system and reward-driven behaviour control
Berland, C. (2018) · theses.fr (ABES) · doi:10.70675/3a1dc076z7d5az413czbc66z525614a40de5
Mécanismes moléculaires du transport de la leptine par les tanycytes hypothalamiques
Millet, M. (2020) · theses.fr (ABES) · doi:10.70675/55aeffdfz5f61z4695zb9ccz0f1450d0e8de
Hormonal Regulation of Food Intake
Breton, J., Langlois, L. D., Coëffier, M., & Achamrah, N. (2026) · Endocrinology · doi:10.1007/978-3-030-71067-5_2-1
Jovanovic, V. M., Narisu, N., Bonnycastle, L. L., Castellano, D., Ryu, S., Tharakan, R., Mesch, K. T., Chen, Q., Erol, F. M. B., Glover, H. J., et al. (2026) · Stem Cell Reports · doi:10.1016/j.stemcr.2026.102958
Pancreatic hormones and the gut-brain axis
Khoshnam, A., Bashir, F., Abediankenari, F., Kherad, M. E., Rahmanian, M., & Deravi, N. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-30263-3.00036-1
Ashtary‐Larky, D. (2026) · Current Obesity Reports · doi:10.1007/s13679-026-00751-2
Metadata
- Authors
- Obici, S., Feng, Z., Karkanias, G., Baskin, D. G., & Rossetti, L.
- Affiliations
- Albert Einstein College of Medicine (US)
- University of Washington (US)
- Corresponding author
- Rossetti, Luciano
- Venue
- Nature Neuroscience
- Published
- 2002-05-20
- Volume
- 5
- Issue
- 6
- Pages
- 566-572
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1997565232
- Cited by
- 719
- References
- 36
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 5 · 2023: 16 · 2022: 22 · 2021: 29 · 2020: 27 · 2019: 37 · 2018: 26 · 2017: 37 · 2016: 33 · 2015: 29 · 2014: 38 · 2013: 37 · 2012: 44
- FWCI
- 10.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-48321, DK-17047, DK20541, DK-45024, P30DK017047)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- hyperphagia, insulin resistance, arcuate nucleus, antisense oligodeoxynucleotides, energy balance, food intake regulation, fat mass, hepatic insulin action, glucose production, insulin signaling
- MeSH terms
- Adipose Tissue, Animals, Arcuate Nucleus of Hypothalamus, Eating, Glucose, Hyperphagia, Hypothalamus, Injections, Intraventricular, Insulin, Insulin Resistance, Liver, Male, Neuropeptide Y, Proteins, Receptor, Insulin, Oligonucleotides, Antisense, Rats, Sprague-Dawley, Intercellular Signaling Peptides and Proteins, Rats, Agouti-Related Protein
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