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Related Concept Videos

Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
GPCRs Regulate Adenylyl Cylase Activity01:09

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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
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Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Related Experiment Video

Updated: Jul 13, 2026

Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells
09:16

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Published on: April 20, 2017

Peptide binding at the GLP-1 receptor.

R Mann1, N Nasr, D Hadden

  • 1Institute of Membrane and Systems Biology, LIGHT Laboratories, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.

Biochemical Society Transactions
|July 20, 2007
PubMed
Summary

Glucagon-like peptide-1 receptor (GLP-1R) binding differs between GLP-1 and exendin-4. Exendin-4 binds the N-domain, unlike GLP-1, revealing key differences in GLP-1R agonist interactions.

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Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
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Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay

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Last Updated: Jul 13, 2026

Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells
09:16

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Published on: April 20, 2017

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Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
11:49

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay

Published on: July 28, 2014

Area of Science:

  • Molecular Pharmacology
  • Biochemistry
  • Endocrinology

Background:

  • The glucagon-like peptide-1 receptor (GLP-1R) is a Family B G-protein-coupled receptor (GPCR).
  • GLP-1R has an N-terminal extracellular domain (N-domain) and a core domain with seven transmembrane helices.
  • The two-domain model suggests the N-domain provides binding energy, while the core domain mediates ligand interaction and signal transduction.

Purpose of the Study:

  • To investigate differential binding properties of GLP-1 receptor agonists, GLP-1 and exendin-4 (EX-4).
  • To understand why EX-4 retains high affinity when truncated, unlike GLP-1.
  • To elucidate why EX-4 binds the isolated N-domain, while GLP-1 does not.

Main Methods:

  • Studied interactions between full-length and truncated GLP-1 receptor ligands (GLP-1, EX-4).
  • Investigated binding affinities with full-length and truncated GLP-1 receptors.
  • Compared binding characteristics of GLP-1 and EX-4 to isolated receptor domains.

Main Results:

  • Exendin-4 (EX-4) retains high affinity with N-terminal truncation, unlike full-length GLP-1.
  • EX-4 binds the isolated N-domain with high affinity, whereas GLP-1 does not.
  • These findings highlight distinct binding mechanisms for GLP-1 and EX-4 at the GLP-1 receptor.

Conclusions:

  • GLP-1 receptor agonists exhibit differential binding modes.
  • The N-domain plays a crucial role in EX-4 binding, but not GLP-1.
  • Understanding these differences is key for developing targeted GLP-1R therapies.