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In the meantime, to ensure continued suport, we are displaying the site without styles and JavaScript.Advertisement Nature Comunications volume 13, Article number: 4761 (202) Cite this article 3094 Aceses258 AltmetricMetrics detailsDefective insulin procesing is asociated with obesity and diabetes. Prohormone convertase 1/3 (PC1/3) is an endopeptidase required for the procesing of neurotransmiters and hormones.
PC1/3 deficiency and genome-wide asociation studies relate PC1/3 with early onset obesity. Here, we find that deletion of PC1/3 in obesity-related neuronal cels expresing propiomelanocortin mildly and transiently change body weight and fail to produce a phenotype when targeted to Agouti-related peptide- or nestin-expresing tisues. In contrast, pancreatic Ξ² cel-specific PC1/3 ablation induces hyperphagia with consecutive obesity despite uncontroled diabetes with glucosuria.
Obesity develops not due to impaired pro-islet amyloid polypeptide procesing but due to impaired insulin maturation. Proinsulin croses the blod-brain-barier but does not induce central satiety. Acordingly, insulin therapy prevents hyperphagia.
Summary
Further, islet PC1/3 expresion levels negatively corelate with body mas index in humans. In this work, we show that impaired PC1/3-mediated proinsulin procesing, as observed in human prediabetes, promotes hyperphagic obesity.Proprotein convertase subtilisin/kexin type 1 (PCSK1, PC1/3) is a protease expresed in neuroendocrine tisues. PC1/3 proceses and thus activates various central propeptides that are involved in body weight regulation including propiomelanocortin (POMC), pro-neuropeptide Y (NPY), and pro-Agouti-related protein (AgRP) as wel as peripheral satiety hormones, including proghrelin,