ArticleNature communications2022
Prohormone convertase 1/3 deficiency causes obesity due to impaired proinsulin processing.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
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- Targeting angiopoietin-like protein 3 and interleukin-1β alleviated liver and kidney injury through attenuation of lipotoxicity and regulation of glycolipid metabolism in db/db mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.Nature communications · 2026Article
- Single-cell virtual knockout network perturbation prioritizes candidate regulators of beta-cell functional failure in type 2 diabetes.Frontiers in endocrinology · 2026Article
- Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling.Structure (London, England : 1993) · 2025Article
- An Antibody Cocktail-Based Immunoaffinity-LC-MS Method Enabled Ultra-Sensitive and Robust Quantification of Circulating Proinsulin Proteoforms and C-Peptide.Analytical chemistry · 2025Article
- The effects of primary cilia-mediated mechanical stimulation on nestinJournal of advanced research · 2025Article
- Weight loss mediates improvement in proinsulin processing during GLP-1 receptor agonist treatment.Diabetology & metabolic syndrome · 2025Article
- Genomics reveals eleven obesity endotypes with distinct biological and phenotypic signatures.medRxiv : the preprint server for health sciences · 2025Article
- doc2a and doc2b contribute to locomotor and social behaviors by down-regulating npas4b in zebrafish.BMC biology · 2025Article
- Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells.Stem cell reports · 2025Article
- The role of the farnesoid X receptor in diabetes and its complications.Molecular and cellular biochemistry · 2025Review
- Review
- Distinct transcriptomic effects of intermittent and chronic caloric restriction in mammary fat pad of a breast cancer mouse model.PloS one · 2025Article
- Ablation of PC1/3 in POMC-Expressing Tissues but Not in Immune Cells Induces Sepsis Hypersensitivity.Journal of the Endocrine Society · 2024Article
- Identification and functional validation of rare coding variants in genes linked to monogenic obesity.Obesity (Silver Spring, Md.) · 2024Article
- Implications of noncoding regulatory functions in the development of insulinomas.Cell genomics · 2024Article
- Article
- The Role of G Protein-Coupled Receptors and Receptor Kinases in PancreaticPharmacological reviews · 2024Review
- Cystine/glutamate antiporter System xDiabetologia · 2023Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defective insulin processing is associated with obesity and diabetes. Prohormone convertase 1/3 (PC1/3) is an endopeptidase required for the processing of neurotransmitters and hormones. PC1/3 deficiency and genome-wide association studies relate PC1/3 with early onset obesity. Here, we find that deletion of PC1/3 in obesity-related neuronal cells expressing proopiomelanocortin mildly and transiently change body weight and fail to produce a phenotype when targeted to Agouti-related peptide- or nestin-expressing tissues. In contrast, pancreatic β cell-specific PC1/3 ablation induces hyperphagia with consecutive obesity despite uncontrolled diabetes with glucosuria. Obesity develops not due to impaired pro-islet amyloid polypeptide processing but due to impaired insulin maturation. Proinsulin crosses the blood-brain-barrier but does not induce central satiety. Accordingly, insulin therapy prevents hyperphagia. Further, islet PC1/3 expression levels negatively correlate with body mass index in humans. In this work, we show that impaired PC1/3-mediated proinsulin processing, as observed in human prediabetes, promotes hyperphagic obesity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.