Updating the Role of α-Cell Preproglucagon products on GLP-1 receptor–mediated insulin secretion
Open accessAbstract
While the field of islet biology has historically focused its attention on understanding β-cell function and the mechanisms by which these cells become dysfunctional with diabetes, there has been a scientific shift toward greater understanding of other endocrine cells of the islet and their paracrine role in regulating the β-cell. In recent years, many questions and new data have come forward regarding the paracrine role of the α-cell and specifically preproglucagon peptides in regulating insulin secretion. The role of intestinally secreted glucagon-like peptide 1 (GLP-1) in regulation of insulin secretion has been questioned, and a physiological role of pancreatic GLP-1 in regulation of insulin secretion has been proposed. In addition, in the last 2 years, a series of studies demonstrated a physiological role for glucagon, acting via the GLP-1 receptor, in paracrine regulation of insulin secretion. Altogether, this work challenges the textbook physiology of both GLP-1 and glucagon and presents a critical paradigm shift for the field. This article addresses these new findings surrounding α-cell preproglucagon products, with a particular focus on GLP-1, in the context of their roles in insulin secretion and consequently glucose metabolism.
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- Authors
- Sandoval, D.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Sandoval, Darleen
- ORCID
- Sandoval, Darleen
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2020-10-14
- Volume
- 69
- Issue
- 11
- Pages
- 2238-2245
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC7576561
- OpenAlex
- W3094120398
- Cited by
- 12
- References
- 66
- Citations by year
- 2026: 1 · 2025: 3 · 2022: 3 · 2021: 5
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK117635, DK121995, DK107282)
- American Diabetes Association (1-19-IBS-252)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- alpha cells, preproglucagon, glucagon-like peptide-1, GLP-1 receptor, insulin secretion, paracrine regulation, glucagon, pancreatic islets, pancreatic beta cells, glucose metabolism, endocrine cells
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Gene Expression Regulation, Humans, Insulin, Glucagon-Secreting Cells, Proglucagon
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