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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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“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]
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“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
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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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