PMID-17928588 – The Physiology of Glucagon-Like Peptide 1
Holst JJ. The Physiology of Glucagon-Like Peptide 1. Physiol Rev. 2007;87(4):1409-1439.
Quick Reference
| Property | Value |
|---|---|
| PMID | 17928588 |
| DOI | 10.1152/physrev.00034.2006 |
| Year | 2007 |
| Journal | Physiological Reviews |
| Study Type | Narrative Review |
| Evidence Level | V |
| Sample | N/A (comprehensive review) |
| Peptide(s) Studied | GLP-1 (Native) |
Key Findings
- GLP-1 is produced by post-translational processing of proglucagon in intestinal L-cells, with GLP-1(7-36) amide being the primary bioactive form
- GLP-1 potentiates glucose-dependent insulin secretion via cAMP/PKA and Epac2 signaling pathways at the pancreatic beta-cell
- GLP-1 suppresses glucagon secretion from alpha-cells, contributing significantly to its glucose-lowering effect
- The peptide delays gastric emptying, which blunts postprandial glucose excursions independently of its insulinotropic action
- DPP-4 rapidly degrades circulating GLP-1 (half-life ~2 minutes), making the native peptide impractical as a therapeutic but validating the DPP-4 inhibitor drug class
- Central GLP-1 receptor activation in the hypothalamus and brainstem reduces appetite and food intake, establishing the basis for GLP-1RA obesity therapies
Study Design
Comprehensive narrative review synthesizing decades of GLP-1 research from the Holst laboratory and the broader field. Covers molecular biology, secretion physiology, receptor pharmacology, and organ-level effects across the pancreas, GI tract, cardiovascular system, and CNS.
Limitations
- Published in 2007, predates the clinical development of long-acting GLP-1 receptor agonists (semaglutide, tirzepatide) and their landmark obesity/CV outcomes trials
- Primarily integrates preclinical and early clinical data; does not address large-scale human efficacy or safety outcomes
- Single-author review reflecting the perspective of one (albeit leading) research group
Clinical Relevance
This is the foundational reference for understanding GLP-1 physiology. It explains why GLP-1 receptor agonists work for diabetes and obesity at a mechanistic level, and why DPP-4 inhibitors were developed. Essential background for any clinician prescribing incretin-based therapies or counseling patients on GLP-1 mimetic peptides and nutraceutical approaches to enhancing endogenous GLP-1 secretion.
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#research #narrative-review #glp-1 #evidence-level-V