Ghrelin Receptor Found Predominantly in Pancreatic PP Cells, With Expression Changed by Diabetes
The ghrelin receptor (GHSR) is predominantly co-expressed with pancreatic polypeptide (PP) in pancreatic islets of both mice and humans, and is upregulated in beta cells by type 2 diabetes, revealing PP cells as key ghrelin/LEAP2 targets.
Quick Facts
What This Study Found
In mice, 85% of GHSR-expressing islet cells coexpress PP and 50% coexpress SST. In humans, 59% coexpress PPY and 95% coexpress SST. GHSR expression is upregulated in beta cells by T2DM. LEAP2 and GHSR antagonists elevated plasma PP.
Key Numbers
85% GHSR cells coexpress PP (mouse); 59% in human; 95% coexpress SST (mouse); GHSR upregulated in T2D beta cells; LEAP2 elevates plasma PP
How They Did This
Histochemical analysis using Ghsr-IRES-Cre reporter mice. Single-cell transcriptomics of mouse and human pancreas. Plasma PP correlations with fat mass and LEAP2. PP response to GHSR antagonist and LEAP2 administration.
Why This Research Matters
Understanding where ghrelin acts in the pancreas is critical for developing ghrelin-based diabetes therapies. Finding PP cells as primary targets redefines how ghrelin and LEAP2 regulate pancreatic function.
The Bigger Picture
The ghrelin-LEAP2 system is emerging as a key metabolic regulatory axis. Identifying PP cells as primary pancreatic targets adds complexity to our understanding and could influence the design of ghrelin-based therapies for diabetes and obesity.
What This Study Doesn't Tell Us
Reporter mouse approach may not capture all GHSR-expressing cells. Single-cell transcriptomics detects mRNA, which may not perfectly reflect protein expression. Human data from multiple datasets with variable methodology. Functional significance of GHSR on PP cells needs testing.
Questions This Raises
- ?What is the functional consequence of ghrelin acting on PP cells versus beta cells?
- ?Does the diabetes-induced GHSR upregulation in beta cells contribute to disease progression?
- ?Could targeting the ghrelin receptor on PP cells provide metabolic benefits?
Trust & Context
- Key Stat:
- 85% PP cell coexpression The majority of ghrelin receptor-expressing cells in mouse pancreas coexpress pancreatic polypeptide, making PP cells — not beta cells — the primary ghrelin targets
- Evidence Grade:
- Moderate evidence: comprehensive approach combining reporter mice, single-cell transcriptomics, and pharmacological studies in both species.
- Study Age:
- Published 2021. The ghrelin-LEAP2 regulatory system continues to be actively studied for metabolic applications.
- Original Title:
- High Coexpression of the Ghrelin and LEAP2 Receptor GHSR With Pancreatic Polypeptide in Mouse and Human Islets.
- Published In:
- Endocrinology, 162(10) (2021)
- Authors:
- Gupta, Deepali(3), Dowsett, Georgina K C, Mani, Bharath K(4), Shankar, Kripa, Osborne-Lawrence, Sherri, Metzger, Nathan P, Lam, Brian Y H, Yeo, Giles S H, Zigman, Jeffrey M
- Database ID:
- RPEP-05430
Evidence Hierarchy
Frequently Asked Questions
What is ghrelin and why does it matter for diabetes?
Ghrelin is a peptide hormone that signals hunger and affects insulin release from the pancreas. Understanding exactly which pancreatic cells have ghrelin receptors is important for developing drugs that target this system for diabetes and obesity treatment.
What is LEAP2?
LEAP2 (liver-expressed antimicrobial peptide 2) is a natural antagonist of the ghrelin receptor. It blocks ghrelin's hunger-promoting effects and is being studied as a potential anti-obesity target. This study shows LEAP2 also affects pancreatic PP cells.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-05430APA
Gupta, Deepali; Dowsett, Georgina K C; Mani, Bharath K; Shankar, Kripa; Osborne-Lawrence, Sherri; Metzger, Nathan P; Lam, Brian Y H; Yeo, Giles S H; Zigman, Jeffrey M. (2021). High Coexpression of the Ghrelin and LEAP2 Receptor GHSR With Pancreatic Polypeptide in Mouse and Human Islets.. Endocrinology, 162(10). https://doi.org/10.1210/endocr/bqab148
MLA
Gupta, Deepali, et al. "High Coexpression of the Ghrelin and LEAP2 Receptor GHSR With Pancreatic Polypeptide in Mouse and Human Islets.." Endocrinology, 2021. https://doi.org/10.1210/endocr/bqab148
RethinkPeptides
RethinkPeptides Research Database. "High Coexpression of the Ghrelin and LEAP2 Receptor GHSR Wit..." RPEP-05430. Retrieved from https://rethinkpeptides.com/research/gupta-2021-high-coexpression-of-the
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.