ArticleJCI insight2021
GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Genetic Determinants of Coronary Artery Disease in Type 2 Diabetes Mellitus Among Asian Populations: A Meta-Analysis.Medical sciences (Basel, Switzerland) · 2026Pooled it
- β-cell 14-3-3-ζ and sex are key regulators of α-cell form and function.Endocrinology · 2026Article
- Transcriptomic changes in the jerboa supraoptic nucleus during osmotic stress: PCSK1 and PTPRN changes are conserved across desert and mesic species.Journal of neuroendocrinology · 2026Article
- Glucagon-like peptide-1 receptor agonists and pancreatic outcomes in chronic pancreatitis: a real-world cohort study.BMC gastroenterology · 2026Article
- Pancreatic Islet Cell Crosstalk: Insight Into α-/β-Cell Compensatory Mechanisms.Comprehensive Physiology · 2026Article
- Sodium-glucose cotransporter 2 inhibitors facilitate cell phenotype conversion of alpha cells through progenitors to beta cells by activating Ppargc1α in diabetic mice.Chinese medical journal · 2026Article
- RNA binding protein HuD regulates the biosynthesis of glucagon-like peptide 1 in intestinal L-cells.Biochemistry and biophysics reports · 2026Article
- Integrating bile acid metabolism into precision nutrition strategies for improved swine performance.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Review
- In vivo functional profiling and structural characterization of the humanScience advances · 2026Article
- Evaluation of distinct and similar pathological features between diabetes and Alzheimer's disease.EXCLI journal · 2026Review
- Hyperuricemia was associated with metabolic response against brain injury instead of metabolism syndrome in Tibet: a cross-sectional analysis.Frontiers in endocrinology · 2026Article
- Advantage of Semaglutide: Comprehensive Analysis of Metabolic Impact of Semaglutide-Treated and Pair-Fed Rats.Comprehensive physiology · 2025Article
- Human pancreatic α-cell heterogeneity and trajectory inference analyses reveal SMOC1 as a β-cell dedifferentiation gene.Nature communications · 2025Article
- α cells use both PC1/3 and PC2 to process proglucagon peptides and control insulin secretion.Science advances · 2025Article
- Glucagon-Like Peptide 1 (GLP-1) Action on Hypothalamic Feeding Circuits.Endocrinology · 2025Review
- Article
- Islet hormones at the intersection of glucose and amino acid metabolism.Nature reviews. Endocrinology · 2025Review
- Huanglian-Renshen-Decoction Maintains Islet β-Cell Identity in T2DM Mice through Regulating GLP-1 and GLP-1R in Both Islet and Intestine.Chinese journal of integrative medicine · 2025Article
- Bi-Hormonal Endocrine Cell Presence Within the Islets of Langerhans of the Human Pancreas Throughout Life.Cells · 2025Article
- Quantitative analysis of islet prohormone convertase 1/3 expression in human pancreas donors with diabetes.Diabetologia · 2024Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that potentiates glucose-stimulated insulin secretion. GLP-1 is classically produced by gut L cells; however, under certain circumstances α cells can express the prohormone convertase required for proglucagon processing to GLP-1, prohormone convertase 1/3 (PC1/3), and can produce GLP-1. However, the mechanisms through which this occurs are poorly defined. Understanding the mechanisms by which α cell PC1/3 expression can be activated may reveal new targets for diabetes treatment. Here, we demonstrate that the GLP-1 receptor (GLP-1R) agonist, liraglutide, increased α cell GLP-1 expression in a β cell GLP-1R-dependent manner. We demonstrate that this effect of liraglutide was translationally relevant in human islets through application of a new scRNA-seq technology, DART-Seq. We found that the effect of liraglutide to increase α cell PC1/3 mRNA expression occurred in a subcluster of α cells and was associated with increased expression of other β cell-like genes, which we confirmed by IHC. Finally, we found that the effect of liraglutide to increase bihormonal insulin+ glucagon+ cells was mediated by the β cell GLP-1R in mice. Together, our data validate a high-sensitivity method for scRNA-seq in human islets and identify a potentially novel GLP-1-mediated pathway regulating human α cell function.
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Registered trials
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.