The melanocortin system and insulin resistance in humans: insights from a patient with complete POMC deficiency and type 1 diabetes mellitus
| Autor: | Sayali A. Ranadive, Janelle A. Noble, Christian Vaisse, Inmaculada Valle, Ivy R. Aslan, Sobha Kollipara |
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| Rok vydání: | 2012 |
| Předmět: |
POMC mutation
Male Pediatric Obesity Pro-Opiomelanocortin Endocrinology Diabetes and Metabolism medicine.medical_treatment Medicine (miscellaneous) Weight Gain Medical and Health Sciences Energy homeostasis insulin resistance Glucose homeostasis Homeostasis Child Nutrition and Dietetics biology Diabetes digestive oral and skin physiology medicine.anatomical_structure Melanocortin Sequence Analysis hormones hormone substitutes and hormone antagonists Type 1 endocrine system medicine.medical_specialty Genotype melanocortin system Article Education Endocrinology & Metabolism Insulin resistance Central melanocortin system Proopiomelanocortin Clinical Research Internal medicine Diabetes Mellitus Genetics medicine Humans Obesity Metabolic and endocrine Nutrition Melanocortins business.industry Insulin DNA Feeding Behavior Sequence Analysis DNA medicine.disease Endocrinology Diabetes Mellitus Type 1 biology.protein Insulin Resistance business Energy Metabolism type 1 diabetes mellitus Adrenal Insufficiency |
| Zdroj: | International journal of obesity (2005), vol 38, iss 1 |
| ISSN: | 1476-5497 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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