title: The melanocortin system and insulin resistance in humans: insights from a patient with complete POMC deficiency and type 1 diabetes mellitus.
abstract: 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.
authors: Children's Hospital Oakland & Research Center Institute, San Francisco, CA, USA.
authors: I R
authors: IR
authors: Aslan
authors: Palo Alto Medical Foundation, San Francisco, CA, USA.
authors: S A
authors: SA
authors: Ranadive
authors: Department of Medicine and Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
authors: I
authors: I
authors: Valle
authors: Keiser Permanente, Roseville, San Francisco, CA, USA.
authors: S
authors: S
authors: Kollipara
authors: Children's Hospital Oakland & Research Center Institute, San Francisco, CA, USA.
authors: J A
authors: JA
authors: Noble
authors: Department of Medicine and Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
authors: C
authors: C
authors: Vaisse
mesh_terms: D000309:Adrenal Insufficiency / Q000150:complications / Q000235:genetics*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004734:Energy Metabolism; D005247:Feeding Behavior; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D053486:Melanocortins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000235:genetics*; D063766:Pediatric Obesity / Q000209:etiology / Q000235:genetics*; D011333:Pro-Opiomelanocortin / Q000172:deficiency* / Q000235:genetics; D017422:Sequence Analysis, DNA; D015430:Weight Gain / Q000235:genetics
chemical_list: D053486:Melanocortins; D011333:Pro-Opiomelanocortin
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