Incretin Action in the Pancreas: Potential Promise, Possible Perils, and Pathological Pitfalls
Open accessAbstract
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones that control the secretion of insulin, glucagon, and somatostatin to facilitate glucose disposal. The actions of incretin hormones are terminated via enzymatic cleavage by dipeptidyl peptidase-4 (DPP-4) and through renal clearance. GLP-1 and GIP promote β-cell proliferation and survival in rodents. DPP-4 inhibitors expand β-cell mass, reduce α-cell mass, and inhibit glucagon secretion in preclinical studies; however, whether incretin-based therapies sustain functional β-cell mass in human diabetic subjects remains unclear. GLP-1 and GIP exert their actions predominantly through unique G protein-coupled receptors expressed on β-cells and other pancreatic cell types. Accurate localization of incretin receptor expression in pancreatic ductal or acinar cells in normal or diabetic human pancreas is challenging because antisera used for detection of the GLP-1 receptor often are neither sufficiently sensitive nor specific to yield reliable data. This article reviews recent advances and controversies in incretin hormone action in the pancreas and contrasts established mechanisms with areas of uncertainty. Furthermore, methodological challenges and pitfalls are highlighted and key areas requiring additional scientific investigation are outlined.
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Early studies suggested more widespread expression of the GLP-1 receptor on a range of cell populations within the kidney using antibodies that were subsequently considered to be nonspecific.
“Early studies suggested more widespread expression of the GLP-1 receptor on a range of cell populations within the kidney using antibodies that were subsequently considered to be nonspecific (11).”
From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [11]
The section “Localization of Incretin Receptor Expression in the Pancreas” says that many GLP-1R antibodies lack specificity and that reported expression in some tissues therefore needs verification. It discusses examples in the pancreas and heart, but does not report early claims of widespread expression across kidney cell populations. The baby hamster kidney cells mentioned in a figure are transfected test cells, not evidence of receptor localization within the kidney. (LLM, conf=0.85)
Experimental — accuracy not yet measuredMost antibodies against the GLP-1 receptor are not considered highly specific, and there remains substantial controversy about the precise protein-level expression of the GLP-1 receptor in the kidney.
“Most antibodies against the GLP-1 receptor are not considered to be highly specific (11), and there remains substantial controversy as to the precise expression of the GLP-1 receptor at the protein level in the kidney.”
From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [11]
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- Authors
- Drucker, D. J.
- Affiliations
- Mount Sinai Hospital (CA)
- Corresponding author
- Drucker, Daniel J.
- ORCID
- Drucker, Daniel J.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2013-09-17
- Volume
- 62
- Issue
- 10
- Pages
- 3316-3323
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3781450
- OpenAlex
- W2107824623
- Cited by
- 272
- References
- 95
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 13 · 2023: 7 · 2022: 7 · 2021: 8 · 2020: 15 · 2019: 15 · 2018: 21 · 2017: 28 · 2016: 32 · 2015: 47 · 2014: 56 · 2013: 10
- FWCI
- 8.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (82700, 123391)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Keywords
- incretins, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, dipeptidyl peptidase IV, DPP-4 inhibitors, beta-cell mass, beta-cell proliferation, glucagon secretion, alpha-cell mass, GLP-1 receptor, G protein-coupled receptors, insulin secretion, renal clearance
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Animals, Diabetes Mellitus, Female, Gastric Inhibitory Polypeptide, Cricetinae, Humans, Inflammation, Male, Pancreas, Receptors, Gastrointestinal Hormone, Blotting, Western, Receptors, Glucagon, Cell Proliferation, Atherosclerosis, Insulin-Secreting Cells, Mice, Rats, Glucagon-Like Peptide 1, Incretins, Dipeptidyl-Peptidase IV Inhibitors, Real-Time Polymerase Chain Reaction, Acinar Cells
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