π Diabetes Management
Prohormone convertase 1/3 deficiency causes obesity due to impaired proinsulin processing - Nature.com
π
Wed, 12 Oct 2022β± 1 min readπ Article
Overview
Thank you for visiting nature.com. You are using a browser version with limited suport for CS. To obtain the best experience, we recomend you use a more up to date browser (or turn of compatibility mode in Internet Explorer).
Key Information
In the meantime, to ensure continued suport, we are displaying the site without styles and JavaScript.Advertisement Nature Comunications volume 13, Article number: 4761 (2022) Cite this article 3094 Aceses258 AltmetricMetrics detailsDefective insulin procesing is associated 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,
Frequently Asked Questions
β What is diabetes and how does it develop?
Diabetes is a metabolic condition where the body cannot properly regulate blood sugar levels. Type 1 results from insufficient insulin production, while Type 2 develops when cells become resistant to insulin. Risk factors include genetics, obesity, sedentary lifestyle, and age.
β What are the main symptoms of diabetes?
Common symptoms include excessive thirst, frequent urination, unexplained weight loss, fatigue, blurred vision, and slow-healing wounds. Type 1 symptoms develop rapidly, while Type 2 symptoms may appear gradually. Many people have no symptoms initially, which is why screening is important.
β How is diabetes diagnosed and monitored?
Diagnosis involves blood tests measuring fasting glucose, HbA1c levels, and glucose tolerance. Regular monitoring typically includes fasting glucose tests and HbA1c measurements every 3-6 months. Continuous glucose monitors provide real-time tracking for better diabetes management.
β What lifestyle changes help manage diabetes?
Effective management includes regular physical activity (150+ minutes weekly), maintaining healthy weight, following a balanced diet with whole grains and lean proteins, managing stress, and getting adequate sleep. These changes can significantly improve blood sugar control and reduce complications.
β When should someone consult a doctor about diabetes?
Consult a healthcare provider if you experience signs of diabetes, have a family history, are overweight, or are over 45. Those with existing diabetes should maintain regular check-ups every 3-6 months to monitor control and adjust treatment as needed.
βοΈ Medical Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.