ArticleDiabetes2011
Normal glucagon signaling and β-cell function after near-total α-cell ablation in adult mice.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 115 citations in OpenAlex.
- Quantification of the glycemic response to microdoses of subcutaneous glucagon at varying insulin levels.Diabetes care · 2014Trial
- Pancreatic α cells are required for nutrient homeostasis by regulating dynamic β cell networks in islets.Science advances · 2026Article
- Alpha-cell glucagon is essential for maintaining β-cell function and identity in adult mice.The Journal of biological chemistry · 2026Article
- Defective HNF1A hinders GLI3 processing favoring duodenal versus pancreatic fate, thus leading to intestinal elongation in vivo.Genes & development · 2026Article
- β-Cell Obligation in α-Cell Glucagon Response to Low Glucose.Research square · 2026Article
- CBP/p300 is critical for the expansion and maintenance of functional pancreatic α cell mass.Nature communications · 2026Article
- Pancreatic α-cell sodium-glucose cotransporter 1 (SGLT1) does not appear to contribute to hyperglucagonemia and glucose intolerance in diabetic mice.Endocrine journal · 2026Article
- Article
- Beta cell-derived cholecystokinin drives obesity-associated pancreatic adenocarcinoma development.Nature communications · 2026Article
- SEL1L-HRD1 ER-associated degradation facilitates prohormone convertase 2 maturation and glucagon production in islet α cells.Nature communications · 2026Article
- Constructing chimeric mouse islets to study alpha- and delta-cell influence on beta-cell feature.Molecular metabolism · 2025Article
- α cells use both PC1/3 and PC2 to process proglucagon peptides and control insulin secretion.Science advances · 2025Article
- Glucagon and Glucose Availability Influence Metabolic Heterogeneity and Malignancy in Pancreatic Neuroendocrine Tumour (pNET) Cells: Novel Routes for Therapeutic Targeting.Molecules (Basel, Switzerland) · 2025Article
- NKX2.2 and KLF4 cooperate to regulate α-cell identity.Genes & development · 2025Article
- Regulated and adaptive in vivo insulin secretion from islets only containing β-cells.Nature metabolism · 2024Article
- Article
- Intra-islet α-cell Gs signaling promotes glucagon release.Nature communications · 2024Article
- Paracrine signalling by pancreatic δ cells determines the glycaemic set point in mice.Nature metabolism · 2024Article
- Beta-cell compensation and gestational diabetes.The Journal of biological chemistry · 2023Review
- Why does the immune system destroy pancreatic β-cells but not α-cells in type 1 diabetes?Nature reviews. Endocrinology · 2023Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo evaluate whether healthy or diabetic adult mice can tolerate an extreme loss of pancreatic α-cells and how this sudden massive depletion affects β-cell function and blood glucose homeostasis. RESEARCH DESIGN AND
methodsWe generated a new transgenic model allowing near-total α-cell removal specifically in adult mice. Massive α-cell ablation was triggered in normally grown and healthy adult animals upon diphtheria toxin (DT) administration. The metabolic status of these mice was assessed in 1) physiologic conditions, 2) a situation requiring glucagon action, and 3) after β-cell loss.
resultsAdult transgenic mice enduring extreme (98%) α-cell removal remained healthy and did not display major defects in insulin counter-regulatory response. We observed that 2% of the normal α-cell mass produced enough glucagon to ensure near-normal glucagonemia. β-Cell function and blood glucose homeostasis remained unaltered after α-cell loss, indicating that direct local intraislet signaling between α- and β-cells is dispensable. Escaping α-cells increased their glucagon content during subsequent months, but there was no significant α-cell regeneration. Near-total α-cell ablation did not prevent hyperglycemia in mice having also undergone massive β-cell loss, indicating that a minimal amount of α-cells can still guarantee normal glucagon signaling in diabetic conditions.
conclusionsAn extremely low amount of α-cells is sufficient to prevent a major counter-regulatory deregulation, both under physiologic and diabetic conditions. We previously reported that α-cells reprogram to insulin production after extreme β-cell loss and now conjecture that the low α-cell requirement could be exploited in future diabetic therapies aimed at regenerating β-cells by reprogramming adult α-cells.
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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.