ArticleTranslational research : the journal of laboratory and clinical medicine2019
Abnormalities in proinsulin processing in islets from individuals with longstanding T1D.
Article in Translational research : the journal of laboratory and clinical medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- Persistence of proinsulin-only secretion in people with long-duration diabetes and minimal residual insulin secretion.Diabetic medicine : a journal of the British Diabetic Association · 2026Article
- Islet Autotransplant Recipients Have Elevated Proinsulin-to-C-Peptide Ratios Supporting Metabolic Stress as a Cause of Islet Attrition.Diabetes · 2026Article
- Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.Nature communications · 2026Article
- Integrated biophysical and spatial remodeling during insulin secretory granule maturation at the mitochondrial network.bioRxiv : the preprint server for biology · 2026Article
- Insulin production is sustained during DNA damage-mediated senescence in adult human beta cells.Diabetologia · 2026Article
- Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling.Structure (London, England : 1993) · 2025Article
- Persisting plasma proinsulin levels in a cohort of 482 individuals with long-standing type 1 diabetes mellitus.Diabetes, obesity & metabolism · 2025Article
- Distribution of Prohormone Convertase 1/3 in β and α Cells of the Human Fetal Pancreas at Gestational Weeks 8-20.Bulletin of experimental biology and medicine · 2025Article
- Distribution of glutathione peroxidase-1 immunoreactive cells in pancreatic islets from type 1 diabetic donors and non-diabetic donors with and without islet cell autoantibodies is variable and independent of disease.Cell and tissue research · 2025Article
- Integrated histopathology of the human pancreas throughout stages of type 1 diabetes progression.bioRxiv : the preprint server for biology · 2025Article
- Detection of Insulin in Insulin-Deficient Islets of Patients with Type 1 Diabetes.Life (Basel, Switzerland) · 2025Article
- Article
- Quantitative analysis of islet prohormone convertase 1/3 expression in human pancreas donors with diabetes.Diabetologia · 2024Article
- Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes.Cell metabolism · 2024Article
- Article
- The beta cell-immune cell interface in type 1 diabetes (T1D).Molecular metabolism · 2023Review
- Article
- SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells.Diabetologia · 2023Article
- The pathogenic "symphony" in type 1 diabetes: A disorder of the immune system, β cells, and exocrine pancreas.Cell metabolism · 2023Review
- Pediatric Type 1 Diabetes: Mechanisms and Impact of Technologies on Comorbidities and Life Expectancy.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 1 country.
Funding
Abstract
We recently described the persistence of detectable serum proinsulin in a large majority of individuals with longstanding type 1 diabetes (T1D), including individuals with undetectable serum C-peptide. Here, we sought to further explore the mechanistic etiologies of persistent proinsulin secretion in T1D at the level of the islet, using tissues obtained from human donors. Immunostaining for proinsulin and insulin was performed on human pancreatic sections from the Network for Pancreatic Organ Donors with Diabetes (nPOD) collection (n = 24). Differential proinsulin processing enzyme expression was analyzed using mass spectrometry analysis of human islets isolated from pancreatic sections with laser capture microdissection (n = 6). Proinsulin processing enzyme mRNA levels were assessed using quantitative real-time PCR in isolated human islets (n = 10) treated with or without inflammatory cytokines. Compared to nondiabetic controls, immunostaining among a subset (4/9) of insulin positive T1D donor islets revealed increased numbers of cells with proinsulin-enriched, insulin-poor staining. T1D donor islets also exhibited increased proinsulin fluorescence intensity relative to insulin fluorescence intensity. Laser capture microdissection followed by mass spectrometry revealed reductions in the proinsulin processing enzymes prohormone convertase 1/3 (PC1/3) and carboxypeptidase E (CPE) in T1D donors. Twenty-four hour treatment of human islets with inflammatory cytokines reduced mRNA expression of the processing enzymes PC1/3, PC2, and CPE. Taken together, these data provide new mechanistic insight into altered proinsulin processing in long-duration T1D and suggest that reduced β cell prohormone processing is associated with proinflammatory cytokine-induced reductions in proinsulin processing enzyme expression.
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