ArticleCell metabolism2022
Heterogenous impairment of α cell function in type 2 diabetes is linked to cell maturation state.
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Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58citing papers in PubMed
16.6field-weighted citation impact, top 1% of its field
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58 citing papers in PubMed, 80 citations in OpenAlex.
- Postnatal refinement of CaChannels (Austin, Tex.) · 2026Article
- Intra-Islet Paracrine Regulation of Glucagon Secretion During Hypoglycemia, Euglycemia, and Hyperglycemia.Annals of the New York Academy of Sciences · 2026Review
- From pancreas and islet resources to diabetes insights.Diabetologia · 2026Review
- eNAMPT induces alpha-cell mass expansion but impaired glucagon counter regulatory response.Endocrinology · 2026Article
- Supervised machine learning identifies impaired mitochondrial quality control in β-cells with development of type 2 diabetes.NPJ systems biology and applications · 2026Article
- Heterogeneous endocrine cell composition defines human islet functional phenotypes.Nature communications · 2026Article
- Single-cell polygenic risk scores dissect cellular and molecular heterogeneity of complex human diseases.Nature biotechnology · 2026Article
- Article
- Single-cell mRNA-regulation analysis reveals cell type-specific mechanisms of type 2 diabetes.Nature communications · 2025Article
- Supervised machine learning identifies impaired mitochondrial quality control in β cells with development of type 2 diabetes.bioRxiv : the preprint server for biology · 2025Article
- Human pancreatic α-cell heterogeneity and trajectory inference analyses reveal SMOC1 as a β-cell dedifferentiation gene.Nature communications · 2025Article
- Molecular Mechanisms of Human Pancreatic Islet Dysfunction Under Overnutrition Metabolic Stress.Diabetes · 2025Article
- Spatially bound functional heterogeneity drives modular organization in β-cell networks.Biophysical journal · 2025Article
- Heterogeneous endocrine cell composition defines human islet functional phenotypes.bioRxiv : the preprint server for biology · 2025Article
- Imeglimin suppresses glucagon secretion and induces a loss of α cell identity.Cell reports. Medicine · 2025Article
- TMEM55A-mediated PI5P signalling regulates alpha cell actin depolymerisation and glucagon secretion.Diabetologia · 2025Article
- Molecular correlates of glycine receptor activity in human β cells.Molecular metabolism · 2025Article
- Amino acid sensing by the α-cell mitochondrial phosphoenolpyruvate cycle regulates intracellular CabioRxiv : the preprint server for biology · 2025Article
- NKX2.2 and KLF4 cooperate to regulate α-cell identity.Genes & development · 2025Article
- 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
Corrections and comments
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Authors and funding
24 authors at 9 institutions in 4 countries.
Xiao-Qing DaiDepartment of Pharmacology, University of Alberta, Edmonton, AB T6G2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada.
Joan Camunas-SolerDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94518, USA.
Linford J B BriantOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, Churchill Hospital, Oxford OX3 7LE, UK.
Theodore Dos SantosDepartment of Pharmacology, University of Alberta, Edmonton, AB T6G2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada.
Aliya F SpigelmanDepartment of Pharmacology, University of Alberta, Edmonton, AB T6G2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada.
Emily M WalkerDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48105, USA.
Rafael Arrojo E DrigoDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA.
Austin BautistaAlberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada.
Robert C JonesDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Dana AvrahamiEndocrinology and Metabolism Department, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel.
James LyonAlberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada.
Aifang NieDepartment of Pharmacology, University of Alberta, Edmonton, AB T6G2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada.
Nancy SmithDepartment of Pharmacology, University of Alberta, Edmonton, AB T6G2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada.
Yongneng ZhangDepartment of Medicine, University of Alberta, Edmonton, AB T6G2R3, Canada.
Janyne JohnsonDepartment of Pharmacology, University of Alberta, Edmonton, AB T6G2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada.
Jocelyn E Manning FoxDepartment of Pharmacology, University of Alberta, Edmonton, AB T6G2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada.
Evangelos D MichelakisDepartment of Medicine, University of Alberta, Edmonton, AB T6G2R3, Canada.
Peter E LightDepartment of Pharmacology, University of Alberta, Edmonton, AB T6G2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada.
Klaus H KaestnerDepartment of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Seung K KimDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University, Stanford, CA 94305, USA.
Patrik RorsmanOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, Churchill Hospital, Oxford OX3 7LE, UK.
Roland W SteinDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA.
Stephen R QuakeDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94518, USA; Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
Patrick E MacDonaldDepartment of Pharmacology, University of Alberta, Edmonton, AB T6G2R3, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G2R3, Canada. Electronic address: pmacdonald@ualberta.ca.
University of Alberta · CAStanford University · USVanderbilt University Medical Center · USChan Zuckerberg Initiative (United States) · USChurchill Hospital · GBHadassah Medical Center · ILOxford Centre for Diabetes, Endocrinology and Metabolism · GBUniversity of Michigan–Ann Arbor · USUniversity of Pennsylvania · US
Funding
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Roland W Stein · 2012 to 2026
$29.3MPenn integrated Human Pancreas procurement and Analysis ProgramUC4DK112217 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI BETTS, MICHAEL R, FELDMAN, MICHAEL D · 2016 to 2020
$17.8MSupplement to Integrated Program for Human Pancreas Procurement and AnalysisUC4DK112232 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ATKINSON, MARK A., POWERS, ALVIN C · 2016 to 2020
$8.4MHuman Pancreas Analysis Program-T2DU01DK123716 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ATKINSON, MARK A., BOTTINO, RITA · 2019 to 2024
$6.6MLinking islet cell function and identity from in vitro to in situU01DK120447 · NIDDK · UNIVERSITY OF ALBERTA · PI ARROJO E DRIGO, RAFAEL, LUNDBERG, EMMA · 2018 to 2021
$3.0MGenetic and physiologic regulation of pig islet development and functionR01DK128932 · NIDDK · STANFORD UNIVERSITY · PI BERGER, TRISH, KIM, SEUNG K · 2021 to 2024
$2.6MIn vivo systems to discover mechanisms regulating human islet alpha cell functionR01DK126482 · NIDDK · STANFORD UNIVERSITY · PI KIM, SEUNG K, MACDONALD, PATRICK · 2020 to 2023
$2.2MDiscovering genetic and hormonal mechanisms underlying diabetes risk from flies to humansR01DK108817 · NIDDK · STANFORD UNIVERSITY · PI KIM, SEUNG K · 2018 to 2022
$2.0MAnalyzing the importance of the MAFB transcription factor in human beta cell activityF32DK109577 · NIDDK · VANDERBILT UNIVERSITY · PI WALKER, EMILY M · 2016 to 2018
$174kMedical Research Council G0801995Medical Research Council MR/V011979/1NIDDK NIH HHS F32 DK109577NIDDK NIH HHS P30 DK020593NIDDK NIH HHS R01 DK108817NIDDK NIH HHS R01 DK126482NIDDK NIH HHS R01 DK128932NIDDK NIH HHS U01 DK120447NIDDK NIH HHS U01 DK123716NIDDK NIH HHS UC4 DK112217NIDDK NIH HHS UC4 DK112232
Abstract
In diabetes, glucagon secretion from pancreatic α cells is dysregulated. The underlying mechanisms, and whether dysfunction occurs uniformly among cells, remain unclear. We examined α cells from human donors and mice using electrophysiological, transcriptomic, and computational approaches. Rising glucose suppresses α cell exocytosis by reducing P/Q-type Ca
Indexed as
Diabetes Mellitus, Type 2Glucagon-Secreting CellsIslets of LangerhansAnimalsExocytosisGlucagonInsulinMiceGlucagonInsulinalpha cellsdiabetesexocytosisglucagonhumanislets of Langerhansmodelingpatch-seq
Identifiers
What Socratic holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.