The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index.
The Central Melanocortin System Can Directly Regulate Serum Insulin Levels*
Abstract
The central melanocortin system has been demonstrated to play a pivotal role in energy homeostasis. Genetic disruption of this system causes obesity in both humans and mice. Previous experiments have shown that centrally-administered melanocortin agonists inhibit food intake and stimulate oxygen consumption. Here we report that centrally-administered melanocortin agonists also inhibit basal insulin release, and alter glucose tolerance. Furthermore, increased plasma insulin levels occur in the young lean MC4-R knockout (MC4-RKO) mouse, and impaired insulin tolerance takes place before the onset of detectable hyperphagia or obesity. These data suggest that the central melanocortin system regulates not only energy intake and expenditure, but also processes related to energy partitioning, as indicated by effects on insulin release and peripheral insulin responsiveness. Previous studies emphasize the role of excess adipose mass in the development of tissue insulin resistance, leading to type II diabetes. The data presented here show that defects in the central control of glucose homeostasis may be an additional factor in some types of obesity-associated type II diabetes.
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In the citing paper
“whereas the melanocortin system directly reduces basal insulin levels by stimulating sympathetic nerve fibers via α-adrenoceptors.116”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [116]
In the citing paper
“Insulin resistance is present before the onset of obesity in melanocortin-4-receptor deficient mice (Fan et al., 2000).”
From Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons (2009) · cites this paper as Fan et al., 2000
Citations
Cites
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030
Self-citationPathogenesis of NIDDM. A balanced overview.
DeFronzo, R. A., Bonadonna, R. C., & Ferrannini, E. (1992) · Diabetes Care · doi:10.2337/diacare.15.3.318 · Cited by 2,085
Role of melanocortinergic neurons in feeding and the agouti obesity syndrome
Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J., & Cone, R. D. (1997) · Nature · doi:10.1038/385165a0 · Cited by 1,924
Self-citationAntagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein
Ollmann, M. M., Wilson, B. D., Yang, Y.-K., Kerns, J. A., Chen, Y., Gantz, I., & Barsh, G. S. (1997) · Science · doi:10.1126/science.278.5335.135 · Cited by 1,881
Krude, H., Biebermann, H., Luck, W., Horn, R., Brabant, G. E., & Grüters, A. (1998) · Nature Genetics · doi:10.1038/509 · Cited by 1,769
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728
Lillioja, S., Mott, D. M., Spraul, M., Ferraro, R., Foley, J. E., Ravussin, E., Knowler, W. C., Bennett, P. H., & Bogardus, C. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312303292703 · Cited by 1,508
A frameshift mutation in MC4R associated with dominantly inherited human obesity
Yeo, G. S. H., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., & O'Rahilly, S. (1998) · Nature Genetics · doi:10.1038/2404 · Cited by 1,159
Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B., & Cone, R. D. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.10.7854347 · Cited by 1,157
Self-citationA frameshift mutation in human MC4R is associated with a dominant form of obesity
Vaisse, C., Clément, K., Guy-grand, B., & Froguel, P. (1998) · Nature Genetics · doi:10.1038/2407 · Cited by 1,091
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1 of the 35 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Patterson, 1999, Chronic infusion of a melanocortin receptor agonist causes weight loss due to decreased food intake and increased metabolic rate., Abstracts Society for Neuroscience, 29th Annual Meeting, Miami Beach, Florida,, 25, 618
- Stair, 1999, Feeding behavior in rats chronically treated with melanocortin agonist, MTII., Abstracts Society for Neuroscience, 29th Annual Meeting, Miami Beach, Florida,, 25, 619
Cited by
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Clinical Spectrum of Obesity and Mutations in the Melanocortin 4 Receptor Gene
Farooqi, I. S., Keogh, J. M., Yeo, G. S. H., Lank, E. J., Cheetham, T., & O'Rahilly, S. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022050 · Cited by 1,778
Anatomy and regulation of the central melanocortin system
Cone, R. D. (2005) · Nature Neuroscience · doi:10.1038/nn1455 · Cited by 1,583
Self-citationPancreatic regulation of glucose homeostasis.
Röder, P. V., Wu, B., Liu, Y., & Han, W. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.6 · Cited by 985
Studies on the Physiological Functions of the Melanocortin System
Cone, R. D. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0034 · Cited by 615
Self-citationFarooqi, I. S., & O’Rahilly, S. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0040 · Cited by 583
Metadata
- Authors
- Fan, W., Dinulescu, D. M., Butler, A. A., Zhou, J., Marks, D. L., & Cone, R. D.
- Affiliations
- Oregon Health & Science University (US)
- Corresponding author
- Cone, Roger D.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2000-09-01
- Volume
- 141
- Issue
- 9
- Pages
- 3072-3079
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2104751353
- Cited by
- 294
- References
- 35
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 7 · 2021: 4 · 2020: 11 · 2019: 8 · 2018: 8 · 2017: 13 · 2016: 13 · 2015: 15 · 2014: 12 · 2013: 15 · 2012: 17
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK055819, P01-DK-55819-01)
- 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 › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- central melanocortin system, melanocortin agonists, insulin secretion, insulin resistance, glucose tolerance, obesity, type 2 diabetes, energy homeostasis, energy allocation, dietary intake, oxygen consumption
- MeSH terms
- alpha-MSH, Animals, Blood Glucose, Body Weight, Central Nervous System, Fatty Acids, Nonesterified, Female, Glucose Tolerance Test, Homeostasis, Insulin, Mice, Inbred C57BL, Mice, Obese, Melanocyte-Stimulating Hormones, Oligopeptides, Signal Transduction, Receptors, Peptide, Mice, Knockout, Receptor, Melanocortin, Type 4, Mice
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