ArticleEndocrinology2020
Differential Effects of Voclosporin and Tacrolimus on Insulin Secretion From Human Islets.
Article in Endocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Investigation of Renal Tissue Deposition of the Calcineurin Inhibitors Voclosporin, Cyclosporine and Tacrolimus Using MALDI-MSI Imaging.Pharmaceutical research · 2026Article
- Post-marketing safety surveillance of voclosporin: an observational, pharmacovigilance study leveraging faers database study on the safety of voclosporin.Frontiers in pharmacology · 2025Article
- Calcineurin inhibitor effects on kidney electrolyte handling and blood pressure: tacrolimus versus voclosporin.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Comparative Effects of GLP-1 and GLP-2 on Beta-Cell Function, Glucose Homeostasis and Appetite Regulation.Biomolecules · 2024Article
- Unveiling islet heterogeneity using an automated microfluidic imaging system.Scientific reports · 2024Article
- Restoration of HMGCS2-mediated ketogenesis alleviates tacrolimus-induced hepatic lipid metabolism disorder.Acta pharmacologica Sinica · 2024Article
- Functional genetics reveals the contribution of delta opioid receptor to type 2 diabetes and beta-cell function.Nature communications · 2024Article
- Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease.Cell metabolism · 2024Article
- HumanIslets: An integrated platform for human islet data access and analysis.bioRxiv : the preprint server for biology · 2024Article
- Induction of diabetes by Tacrolimus in a phenotypic model of obesity and metabolic syndrome.Frontiers in endocrinology · 2024Article
- Article
- Dynamic changes in β-cell [CaMolecular metabolism · 2022Article
- Old and New Calcineurin Inhibitors in Lupus Nephritis.Journal of clinical medicine · 2021Review
- The Human Islet: Mini-Organ With Mega-Impact.Endocrine reviews · 2021Review
- Obesity and Post-Transplant Diabetes Mellitus in Kidney Transplantation.Journal of clinical medicine · 2021Review
- Endoplasmic Reticulum-Mitochondria Crosstalk and Beta-Cell Destruction in Type 1 Diabetes.Frontiers in immunology · 2021Review
- Differential Effects of Voclosporin and Tacrolimus on Insulin Secretion From Human Islets.Endocrinology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The incidence of new onset diabetes after transplant (NODAT) has increased over the past decade, likely due to calcineurin inhibitor-based immunosuppressants, including tacrolimus (TAC) and cyclosporin. Voclosporin (VCS), a next-generation calcineurin inhibitor, is reported to cause fewer incidences of NODAT but the reason is unclear. While calcineurin signaling plays important roles in pancreatic β-cell survival, proliferation, and function, its effects on human β-cells remain understudied. In particular, we do not understand why some calcineurin inhibitors have more profound effects on the incidence of NODAT. We compared the effects of TAC and VCS on the dynamics of insulin secretory function, programmed cell death rate, and the transcriptomic profile of human islets. We studied 2 clinically relevant doses of TAC (10 ng/mL, 30 ng/mL) and VCS (20 ng/mL, 60 ng/mL), meant to approximate the clinical trough and peak concentrations. TAC, but not VCS, caused a significant impairment of 15 mM glucose-stimulated and 30 mM KCl-stimulated insulin secretion. This points to molecular defects in the distal stages of exocytosis after voltage-gated Ca2+ entry. No significant effects on islet cell survival or total insulin content were identified. RNA sequencing showed that TAC significantly decreased the expression of 17 genes, including direct and indirect regulators of exocytosis (SYT16, TBC1D30, PCK1, SMOC1, SYT5, PDK4, and CREM), whereas VCS has less broad, and milder, effects on gene expression. Clinically relevant doses of TAC, but not VCS, directly inhibit insulin secretion from human islets, likely via transcriptional control of exocytosis machinery.
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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 Socratic graph.