ArticlePloS one2011
Insulin and glucagon regulate pancreatic α-cell proliferation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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Who cites it
50 citing papers in PubMed, 76 citations in OpenAlex.
- Hyperglucagonemia and glucagon hypersecretion in early type 2 diabetes result from multifaceted dysregulation of pancreatic mouse α-cells.Pflugers Archiv : European journal of physiology · 2025Article
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- Sex-dependent intra-islet structural rearrangements affecting alpha-to-beta cell interactions lead to adaptive enhancements of CaDiabetologia · 2024Article
- The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.International journal of molecular sciences · 2024Review
- Endocrinology of Taste with Aging.Endocrinology and metabolism clinics of North America · 2023Review
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- Pharmacological blockade of the EP3 prostaglandin EMolecular metabolism · 2021Article
- The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror.International journal of molecular sciences · 2021Review
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- Glucagon Resistance and Decreased Susceptibility to Diabetes in a Model of Chronic Hyperglucagonemia.Diabetes · 2021Article
- Metabolic Role of PTEN in Insulin Signaling and Resistance.Cold Spring Harbor perspectives in medicine · 2020Review
- Endocrine Autoimmune Disease as a Fragility of Immune Surveillance against Hypersecreting Mutants.Immunity · 2020Article
- Paracrine signaling in islet function and survival.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Mechanisms of the Regulation and Dysregulation of Glucagon Secretion.Oxidative medicine and cellular longevity · 2020Review
- Higher glucagon-to-insulin ratio is associated with elevated glycated hemoglobin levels in type 2 diabetes patients.The Korean journal of internal medicine · 2019Article
- Cell Autonomous Dysfunction and Insulin Resistance in Pancreatic α Cells.International journal of molecular sciences · 2019Review
- Which factors determine exocrine pancreatic dysfunction in diabetes mellitus?World journal of gastroenterology · 2019Review
- β-Cell Fate in Human Insulin Resistance and Type 2 Diabetes: A Perspective on Islet Plasticity.Diabetes · 2019Review
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Type 2 diabetes mellitus (T2DM) results from insulin resistance and β-cell dysfunction, in the setting of hyperglucagonemia. Glucagon is a 29 amino acid peptide hormone, which is secreted from pancreatic α cells: excessively high circulating levels of glucagon lead to excessive hepatic glucose output. We investigated if α-cell numbers increase in T2DM and what factor (s) regulate α-cell turnover. Lepr(db)/Lepr(db) (db/db) mice were used as a T2DM model and αTC1 cells were used to study potential α-cell trophic factors. Here, we demonstrate that in db/db mice α-cell number and plasma glucagon levels increased as diabetes progressed. Insulin treatment (EC50 = 2 nM) of α cells significantly increased α-cell proliferation in a concentration-dependent manner compared to non-insulin-treated α cells. Insulin up-regulated α-cell proliferation through the IR/IRS2/AKT/mTOR signaling pathway, and increased insulin-mediated proliferation was prevented by pretreatment with rapamycin, a specific mTOR inhibitor. GcgR antagonism resulted in reduced rates of cell proliferation in αTC1 cells. In addition, blockade of GcgRs in db/db mice improved glucose homeostasis, lessened α-cell proliferation, and increased intra-islet insulin content in β cells in db/db mice. These studies illustrate that pancreatic α-cell proliferation increases as diabetes develops, resulting in elevated plasma glucagon levels, and both insulin and glucagon are trophic factors to α-cells. Our current findings suggest that new therapeutic strategies for the treatment of T2DM may include targeting α cells and glucagon.
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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.