Cited by 294Regulation of Appetite and ObesityPancreatic function and diabetesAdipokines, Inflammation, and Metabolic Diseases

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*

Fan, Wei, Dinulescu, Daniela M., Butler, Andrew A., Zhou, Jeanie, Marks, Daniel L., Cone, Roger D.·2000·Endocrinology

DOI 10.1210/endo.141.9.7665

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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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BindingDB Entry 50016471: Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist.
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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.
ORCID: Fan, Wei
Dinulescu, Daniela M.
Butler, Andrew A.
Marks, Daniel L.
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
DOI: 10.1210/endo.141.9.7665
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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The Central Melanocortin System Can Directly Regulate Serum Insulin Levels*

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