Cited by 143Pancreatic function and diabetesDiabetes and associated disordersDiabetes Treatment and Management

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The α-cell in diabetes mellitus

Gromada, Jesper, Chabosseau, Pauline, Rutter, Guy A.·2018·Nature Reviews Endocrinology

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Abstract

Findings from the past 10 years have placed the glucagon-secreting pancreatic α-cell centre stage in the development of diabetes mellitus, a disease affecting almost one in every ten adults worldwide. Glucagon secretion is reduced in patients with type 1 diabetes mellitus, increasing the risk of insulin-induced hypoglycaemia, but is enhanced in type 2 diabetes mellitus, exacerbating the effects of diminished insulin release and action on blood levels of glucose. A better understanding of the mechanisms underlying these changes is therefore an important goal. RNA sequencing reveals that, despite their opposing roles in the control of blood levels of glucose, α-cells and β-cells have remarkably similar patterns of gene expression. This similarity might explain the fairly facile interconversion between these cells and the ability of the α-cell compartment to serve as a source of new β-cells in models of extreme β-cell loss that mimic type 1 diabetes mellitus. Emerging data suggest that GABA might facilitate this interconversion, whereas the amino acid glutamine serves as a liver-derived factor to promote α-cell replication and maintenance of α-cell mass. Here, we survey these developments and their therapeutic implications for patients with diabetes mellitus.

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Authors: Gromada, J., Chabosseau, P., & Rutter, G. A.
Affiliations: Regeneron (United States) (US)
Hammersmith Hospital (GB)
Corresponding author: Gromada, Jesper
Rutter, Guy A.
ORCID: Gromada, Jesper
Chabosseau, Pauline
Rutter, Guy A.
Venue: Nature Reviews Endocrinology
Publisher: Springer Science and Business Media LLC
Published: 2018-10-11
Volume: 14
Issue: 12
Pages: 694-704
ISSN: 1759-5029 (ISSN-L)
1759-5037
DOI: 10.1038/s41574-018-0097-y
OpenAlex: W2897922438
Cited by: 143
References: 148
Citations by year: 2026: 19 · 2025: 12 · 2024: 17 · 2023: 21 · 2022: 24 · 2021: 27 · 2020: 12 · 2019: 11
FWCI: 2.77
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: Regeneron Pharmaceuticals
National Institute for Health and Care Research (CL-2017-21-002, ACF-2010-21-012)
Academy of Medical Sciences (SGL019\1078)
Servier
Medical Research Council (MR/N00275X/1, MR/M012646/1, MR/K001981/1, MR/L020149/1, MR/R010676/1, MR/N020472/1, MR/R022259/1, MR/K023667/1, MR/R014329/1, MR/L02036X/1)
Biotechnology and Biological Sciences Research Council (BB/J015873/1)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: alpha cells, glucagon secretion, type 1 diabetes, type 2 diabetes, hypoglycemia, GABA, glutamine, beta cell destruction, gene expression, diabetes treatment
MeSH terms: Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Glucagon, Humans, Insulin, Male, Role, Sensitivity and Specificity, Glucagon-Secreting Cells, Insulin-Secreting Cells

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