The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Insulin Action in AgRP-Expressing Neurons Is Required for Suppression of Hepatic Glucose Production
Open accessAbstract
Insulin action in the central nervous system regulates energy homeostasis and glucose metabolism. To define the insulin-responsive neurons that mediate these effects, we generated mice with selective inactivation of the insulin receptor (IR) in either pro-opiomelanocortin (POMC)- or agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus. While neither POMC- nor AgRP-restricted IR knockout mice exhibited altered energy homeostasis, insulin failed to normally suppress hepatic glucose production during euglycemic-hyperinsulinemic clamps in AgRP-IR knockout (IR(DeltaAgRP)) mice. These mice also exhibited reduced insulin-stimulated hepatic interleukin-6 expression and increased hepatic expression of glucose-6-phosphatase. These results directly demonstrate that insulin action in POMC and AgRP cells is not required for steady-state regulation of food intake and body weight. However, insulin action specifically in AgRP-expressing neurons does play a critical role in controlling hepatic glucose production and may provide a target for the treatment of insulin resistance in type 2 diabetes.
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In the citing paper
“insulin hyperpolarizes and silences both AgRP and POMC neurons (96) and activates PI3K signaling in both these neuronal populations (204).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [96]
In the citing paper
“implying a role for insulin action in AgRP expressing cells in the maintenance of normal liver insulin sensitivity (96).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [96]
Citations
Cites
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356
Self-citationRole 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
Self-citationBrüning, J. C., Michael, M. D., Winnay, J. N., Hayashi, T., Hörsch, D., Accili, D., Goodyear, L. J., & Kahn, C. R. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80155-0 · Cited by 1,173
Self-citationMagistretti, P. J., Pellerin, L., Rothman, D. L., & Shulman, R. G. (1999) · Science · doi:10.1126/science.283.5401.496 · Cited by 1,170
NPY/AgRP Neurons Are Essential for Feeding in Adult Mice but Can Be Ablated in Neonates
Luquet, S. H., Perez, F. A., Hnasko, T. S., & Palmiter, R. D. (2005) · Science · doi:10.1126/science.1115524 · Cited by 1,150
Divergence of Melanocortin Pathways in the Control of Food Intake and Energy Expenditure
Balthasar, N., Dalgaard, L. T., Lee, C. E., Yu, J. H., Funahashi, H., Williams, T. B., Ferreira, M. A. R., Tang, V., McGovern, R. A., Kenny, C. D., et al. (2005) · Cell · doi:10.1016/j.cell.2005.08.035 · Cited by 1,107
Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis
Balthasar, N., Coppari, R., McMinn, J., Liu, S. M., Lee, C. E., Tang, V., Kenny, C. D., McGovern, R. A., Chua, S. C., Elmquist, J. K., et al. (2004) · Neuron · doi:10.1016/j.neuron.2004.06.004 · Cited by 935
Hypothalamic insulin signaling is required for inhibition of glucose production
Obici, S., Zhang, B. B., Karkanias, G., & Rossetti, L. (2002) · Nature Medicine · doi:10.1038/nm1202-798 · Cited by 904
Diabetes, Obesity, and the Brain
Schwartz, M. W., & Porte, D. (2005) · Science · doi:10.1126/science.1104344 · Cited by 841
Agouti-related peptide–expressing neurons are mandatory for feeding
Gropp, E., Shanabrough, M., Borók, E., Xu, A. W., Janoschek, R., Buch, T., Plum, L., Balthasar, N., Hampel, B., Waisman, A., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1548 · Cited by 800
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Energy Metabolism in the Liver
Rui, L. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130024 · Cited by 2,401
The PI3K/AKT Pathway in Obesity and Type 2 Diabetes
Huang, X., Liu, G., Guo, J., & Su, Z. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.27173 · Cited by 1,673
“Another way to regulate HGP is PI3K-stimulated generation of PIP3 in AgRP neurons, which activates K (ATP) channels, decreasing G6PC expression in the liver [91].”
BackgroundInfluentialInsulin signaling in osteoblasts integrates bone remodeling and energy metabolism
Ferron, M., Wei, J., Yoshizawa, T., Del Fattore, A., DePinho, R. A., Teti, A., Ducy, P., & Karsenty, G. (2010) · Cell · doi:10.1016/j.cell.2010.06.003 · Cited by 1,123
IL-6 pathway in the liver: From physiopathology to therapy
Schmidt-Arras, D., & Rose-John, S. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.004 · Cited by 881
Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity
Timper, K., & Brüning, J. C. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.026609 · Cited by 851
Self-citation
Metadata
- Authors
- Könner, A. C., Janoschek, R., Plum, L., Jordan, S. D., Rother, E., Ma, X., Xu, C., Enriori, P., Hampel, B., Barsh, G. S., Kahn, C. R., Cowley, M. A., Ashcroft, F. M., & Brüning, J. C.
- Affiliations
- University of Cologne (DE)
- University of Oxford (GB)
- Oregon National Primate Research Center (US)
- Stanford Medicine (US)
- Joslin Diabetes Center (US)
- Corresponding author
- Brüning, Jens C.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 5
- Issue
- 6
- Pages
- 438-449
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2072556905
- Cited by
- 695
- References
- 34
- Citations by year
- 2026: 17 · 2025: 22 · 2024: 38 · 2023: 31 · 2022: 21 · 2021: 58 · 2020: 42 · 2019: 37 · 2018: 44 · 2017: 52 · 2016: 45 · 2015: 38 · 2014: 46 · 2013: 36 · 2012: 33
- FWCI
- 13.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-6-2202)
- National Center for Research Resources (RR-0163)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- insulin action, insulin receptor, agouti-related protein, proopiomelanocortin, arcuate nucleus, hypothalamic neurons, hepatic glucose production, energy homeostasis, dietary intake, body weight, interleukin-6, glucose-6-phosphatase, insulin resistance, type 2 diabetes, hyperinsulinemic-euglycemic clamp
- MeSH terms
- Animals, Body Weight, Electrophysiology, Female, Glucose, Glucose Tolerance Test, Glucose-6-Phosphatase, Homeostasis, Hyperinsulinism, Hypothalamus, Immunoenzyme Techniques, Insulin, Liver, Male, Mice, Inbred C57BL, Neurons, Pro-Opiomelanocortin, Receptor, Insulin, Blotting, Western, Interleukin-6, Phosphatidylinositol Phosphates, Mice, Knockout, Integrases, Phosphatidylinositol 3-Kinases, Mice, Agouti-Related Protein
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