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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]
Citations
Cites
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451
Self-citationCampfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243
Role of Brain Insulin Receptor in Control of Body Weight and Reproduction
Brüning, J. C., Gautam, D., Burks, D. J., Gillette, J., Schubert, M., Orban, P. C., Klein, R., Krone, W., Müller-Wieland, D., & Kahn, C. R. (2000) · Science · doi:10.1126/science.289.5487.2122 · Cited by 2,235
Frederich, R. C., Hamann, A., Anderson, S., Löllmann, B., Lowell, B. B., & Flier, J. S. (1995) · Nature Medicine · doi:10.1038/nm1295-1311 · Cited by 1,660
The role of depot fat in the hypothalamic control of food intake in the rat
Gc, K. (1953) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1953.0009 · Cited by 1,432
Isolated removal of hypothalamic or other brain nuclei of the rat
Palkovits, M. (1973) · Brain Research · doi:10.1016/0006-8993(73)90290-4 · Cited by 1,431
Obese and diabetes: Two mutant genes causing diabetes-obesity syndromes in mice
Coleman, D. L. (1978) · Diabetologia · doi:10.1007/bf00429772 · Cited by 1,307
Insulin receptors are widely distributed in the central nervous system of the rat
Havránková, J., Roth, J., & Brownstein, M. (1978) · Nature · doi:10.1038/272827a0 · Cited by 1,116
Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons
Woods, S. C., Lotter, E. C., McKay, L. D., & Porte, D. (1979) · Nature · doi:10.1038/282503a0 · Cited by 1,114
Rossetti, L., Smith, D. J., Shulman, G. I., Papachristou, D. N., & DeFronzo, R. A. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112981 · Cited by 824
Self-citationA nutrient-sensing pathway regulates leptin gene expression in muscle and fat
Wang, J., Liu, R., Hawkins, M. A., Barzilai, N., & Rossetti, L. (1998) · Nature · doi:10.1038/31474 · Cited by 823
Self-citationInsulin in the Brain: A Hormonal Regulator of Energy Balance*
Schwartz, M. W., Figlewicz, D. P., Baskin, D. G., Woods, S. C., & Porte, D. (1992) · Endocrine Reviews · doi:10.1210/edrv-13-3-387 · Cited by 808
Self-citationKey enzyme in leptin-induced anorexia
Niswender, K. D., Morton, G. J., Stearns, W. H., Rhodes, C. J., Myers, M. G., & Schwartz, M. W. (2001) · Nature · doi:10.1038/35101657 · Cited by 585
Inhibition of hypothalamic neuropeptide Y gene expression by insulin.
Schwartz, M. W., Sipols, A. J., Marks, J. L., Sanacora, G., White, J. D., Scheurink, A., Kahn, S. E., Baskin, D. G., Woods, S. C., & Figlewicz, D. P. (1992) · Endocrinology · doi:10.1210/endo.130.6.1597158 · Cited by 555
Self-citationRecruitment of functional GABAA receptors to postsynaptic domains by insulin
Wan, Q., Xiong, Z., Man, H., Ackerley, C., Braunton, J., Lu, W. Y., Becker, L. E., MacDonald, J. F., & Wang, Y. T. (1997) · Nature · doi:10.1038/41792 · Cited by 537
Chiang, M. Y.-N., Chan, H., Zounes, M. A., Freier, S., Lima, W. F., & Bennett, C. F. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55250-9 · Cited by 463
Sipols, A. J., Baskin, D. G., & Schwartz, M. W. (1995) · Diabetes · doi:10.2337/diab.44.2.147 · Cited by 389 · cited 1×
“and their central administration decreases food intak”
Self-citationCentral melanocortin receptors regulate insulin action
Obici, S., Feng, Z., Tan, J., Liu, L., Karkanias, G., & Rossetti, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200112954 · Cited by 370
Self-citationCentral melanocortin receptors regulate insulin action
Obici, S., Feng, Z., Tan, J., Liu, L., Karkanias, G. B., & Rossetti, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12954 · Cited by 370
Self-citationBaskin, D. G., Figlewicz, D. P., Woods, S. C., Porte, D., & Dorsa, D. M. (1987) · Annual Review of Physiology · doi:10.1146/annurev.ph.49.030187.002003 · Cited by 344
Self-citationLeptin selectively decreases visceral adiposity and enhances insulin action
Barzilai, N., Wang, J., Massilon, D., Vuguin, P., Hawkins, M., & Rossetti, L. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119865 · Cited by 335 · cited 1×
“Hypothalamic and hepatic insulin action To assess the impact of hypothalamic insulin receptor downregulation on the action of insulin, we performed insulin-clamp (3 mU/kg min) studies in conscious rat”
MethodSelf-citationRossetti, L., & Giaccari, A. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114636 · Cited by 246
Self-citationSchwartz, M. W., Marks, J. L., Sipolst, A. J., Basking, D. G., Woods, S. C., Kahn, S. E., & Porte, D. (1991) · Endocrinology · doi:10.1210/endo-128-5-2645 · Cited by 245
Intracerebroventricular Leptin Regulates Hepatic but Not Peripheral Glucose Fluxes
Liu, L., Karkanias, G. B., Morales, J. C., Hawkins, M., Barzilai, N., Wang, J., & Rossetti, L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.47.31160 · Cited by 222
Self-citationBaskin, D. G., Schwartz, M. W., Seeley, R. J., Woods, S. C., Porte, D., Breininger, J. F., Jonak, Z., Schaefer, J., Krouse, M., Burghardt, C., et al. (1999) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215549904700309 · Cited by 200
Self-citationAir, E. L., Strowski, M. Z., Benoit, S. C., Conarello, S., Salituro, G., Guan, X.-M., Liu, K., Woods, S. C., & Zhang, B. B. (2002) · Nature Medicine · doi:10.1038/nm0202-179 · Cited by 169
Specificity Controls for Immunocytochemical Methods
Burry, R. W. (2000) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540004800201 · Cited by 152
Suppression of food intake by intravenous nutrients and insulin in the baboon
Woods, S. C., Stein, L. J., McKay, L. D., & Porte, D. (1984) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1984.247.2.r393 · Cited by 130
Regulation by insulin of a unique neuronal Ca2+ pool and of neuropeptide secretion
Jonas, E. A., Knox, R. J., Smith, T. C. M., Wayne, N. L., Connor, J. A., & Kaczmarek, L. K. (1997) · Nature · doi:10.1038/385343a0 · Cited by 120
The effect of leptin on Lep expression is tissue-specific and nutritionally regulated
Wang, J., Liu, R., Liu, L., Chowdhury, R., Barzilai, N., Tan, J., & Rossetti, L. (1999) · Nature Medicine · doi:10.1038/11335 · Cited by 75
Self-citationLack of Feedback Inhibition of Insulin Secretion in Denervated Human Pancreas
Luzi, L., Battezzati, A., Perseghin, G., Bianchi, E., Vergani, S., Secchi, A., Rocca, E. L., Staudacher, C., Spotti, D., Ferrari, G. C., et al. (1992) · Diabetes · doi:10.2337/diab.41.12.1632 · Cited by 73
Evidence that the brain of the conscious dog is insulin sensitive.
Davis, S. N., Colburn, C., Dobbins, R., Nadeau, S., Neal, D., Williams, P., & Cherrington, A. D. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117703 · Cited by 68
Decreased visceral adiposity accounts for leptin effect on hepatic but not peripheral insulin action
Barzilai, N., She, L., Liu, L., Wang, J., Hu, M., Vuguin, P. M., & Rossetti, L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.2.e291 · Cited by 63
Self-citationInsulin and IGF‐I Receptor Signaling in Cultured Neuronsa
Heidenreich, K. A. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb26207.x · Cited by 56
Robinson, L. J., Leitner, W., Draznin, B., & Heidenreich, K. A. (1994) · Endocrinology · doi:10.1210/endo.135.6.7988444 · Cited by 37
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Rui, L. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130024 · Cited by 2,401
Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H.-Y., Ahima, R. S., Craft, S., Gandy, S., Buettner, C., Stoeckel, L. E., et al. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.185 · Cited by 1,597
Hypothalamic IKKβ/NF-κB and ER Stress Link Overnutrition to Energy Imbalance and Obesity
Zhang, X., Zhang, G., Zhang, H., Karin, M., Bai, H., & Cai, D. (2008) · Cell · doi:10.1016/j.cell.2008.07.043 · Cited by 1,350
Pathogenesis of type 2 diabetes mellitus
DeFronzo, R. A. (2004) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.04.013 · Cited by 1,342
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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