The central melanocortin system is essential for the regulation of long-term energy homeostasis in humans. Rodent experiments suggest that this system also affects glucose metabolism, in particular by modulating peripheral insulin sensitivity independently of its effect on adiposity. Rare patients with complete genetic defects in the central melanocortin system can provide insight into the role of this system in glucose homeostasis in humans. We here describe the eighth individual with complete proopiomelanocortin (POMC) deficiency and the first with coincidental concomitant type 1 diabetes, which provides a unique opportunity to determine the role of melanocortins in glucose homeostasis in human. Direct sequencing of the POMC gene in this severely obese patient with isolated adrenocorticotropic hormone deficiency identified a homozygous 5' untranslated region mutation -11C>A, which we find to abolish normal POMC protein synthesis, as assessed in vitro. The patient's insulin requirements were as expected for his age and pubertal development. This unique patient suggests that in humans the central melanocortin system does not seem to affect peripheral insulin sensitivity, independently of its effect on adiposity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648369 | PMC |
| http://dx.doi.org/10.1038/ijo.2013.53 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways.
Hum Mol Genet
January 2025
Department of Metabolism and Systems Science, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed at hypothalamic neurons that has an important role in appetite suppression and food intake. Mutations in MC4R are the most common cause of monogenic obesity and can affect multiple signaling pathways including Gs-cAMP, Gq, ERK1/2, β-arrestin recruitment, internalization and cell surface expression. The melanocortin-2 receptor accessory protein 2 (MRAP2), is a single-pass transmembrane protein that interacts with and regulates signaling by MC4R.
View Article and Find Full Text PDFPharmacological function of melanocortin-3 receptor in goldfish (Carassius auratus).
Gen Comp Endocrinol
January 2025
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:
The melanocortin-3 receptor (MC3R) was recognized for its critical role in energy metabolism and inflammatory responses in mammals; however, its functions in fish remain poorly understood. This study characterized the mc3r gene in goldfish, investigating its sequence, tissue distribution, and pharmacological responses. The coding sequence of goldfish mc3r was 975 bp, translating to a 325-amino-acid protein typical of G protein-coupled receptors, with notable conservation across cyprinids.
View Article and Find Full Text PDFFemale Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder.
Neuropharmacology
January 2025
Department of Neuroscience, University of Minnesota, Minneapolis, MN, 55455, USA.
Hypoactive sexual desire disorder (HSDD) is the most reported sexual dysfunction among premenopausal women worldwide. Bremelanotide, trade name Vyleesi, has been approved by the United States Food and Drug Administration to treat HSDD. However, despite approval, very little is known about its neurobiological mechanism of action.
View Article and Find Full Text PDFAdvances in pharmacological treatment of Cushings disease.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Endocrinology ＆Metabolism, West China Hospital, Sichuan University, Chengdu 610041.
Cushing's disease is a rare endocrine disorder characterized by hypercortisolism. Chronic elevated cortisol levels can lead to dysfunction or complications in multiple organs of systems, including cardiovascular, glucose, and bone metabolism, severely impacting patients' quality of life and posing life-threatening risks. Surgery is the first-line treatment for Cushing's disease.
View Article and Find Full Text PDFExtracts Exert Anti-Melanogenic Properties via the CREB/MAPK Pathway in B16F10 Cells.
Mar Drugs
November 2024
Research Institute of Basic Sciences, Incheon National University, Incheon 22012, Republic of Korea.
, a salt-tolerant plant, has demonstrated antioxidant effects, the ability to prevent prostate enlargement, antifungal properties, and skin moisturizing benefits. This study aimed to explore the anti-melanogenic potential of the 70% ethanol extract of (TME) along with its ethyl acetate (TME-EA) and water (TME-A) fractions. TME (10-200 µg/mL), TME-EA (1-15 µg/mL), and TME-A (100-1000 µg/mL) were prepared and applied to B16F10 cells with or without α-MSH for 72 h.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!