Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

415
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...
415
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

249
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...
249
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

1.5K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.5K
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

4.0K
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
4.0K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

1.4K
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.
Insulin and C-peptide are...
1.4K
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

256
Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
256

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

QSAR in the Browser: An Interactive Cheminformatics Web Application.

Journal of chemical information and modeling·2026
Same author

Comparison of analgesic efficacy of erector spinae plane block with rhomboid intercostal subserratus plane block in patients undergoing modified radical mastectomy: A randomised control trial.

Indian journal of anaesthesia·2026
Same author

Crediting and citing Indigenous Knowledges within research.

Bioscience·2026
Same author

Characterizing Visual Neurosurgical Expertise in Brain MRI Visualization Using Eye-Tracking and 3D Fractal Dimension Analysis.

Journal of eye movement research·2026
Same author

Consensus on Neonatal and Pediatric Interfacility Transport.

Air medical journal·2026
Same author

Decision-analytic models in the economic evaluation of community health worker programmes globally: a systematic review.

BMJ global health·2026
Same journal

A human-specific genetic modifier reconfigures large-scale cortical network dynamics underlying behavioral performance.

bioRxiv : the preprint server for biology·2026
Same journal

<i>Staphylococcus aureus</i> uses a eukaryotic-like uridyltransferase to make UDP-GlcNAc for cell wall synthesis.

bioRxiv : the preprint server for biology·2026
Same journal

Dynamic redistribution of eIF4F controls cap-dependent translation initiation.

bioRxiv : the preprint server for biology·2026
Same journal

When does additional information improve accuracy of RNA secondary structure prediction?

bioRxiv : the preprint server for biology·2026
Same journal

Normative brain-state trajectories reveal deviation from healthy aging in Alzheimer's disease.

bioRxiv : the preprint server for biology·2026
Same journal

Noradrenergic infraslow rhythm during sleep is the critical link between heart-rate dynamics and memory consolidation.

bioRxiv : the preprint server for biology·2026
See all related articles

Related Experiment Video

Updated: Sep 8, 2025

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate
05:58

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate

Published on: June 25, 2019

7.6K

Receptor Activity-Modifying Protein 3 enhances GLP-1-mediated Insulin Secretion.

Abigail Pearce1, Poonam Kumari2, Claudia M Sisk1

  • 1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK.

Biorxiv : the Preprint Server for Biology
|August 20, 2025
PubMed
Summary
This summary is machine-generated.

Receptor activity-modifying protein 3 (RAMP3) interacts with the Glucagon-like peptide-1 receptor (GLP-1R), altering its signaling to enhance insulin secretion. This discovery may lead to improved GLP-1R therapeutics with fewer side effects.

Keywords:
Allosteric RegulationBiological SciencesCalcium intracellular releaseDiabetesG Protein-coupled ReceptorPharmacologySecond Messengerinsulin secretion

More Related Videos

Homogeneous Time-resolved F&#246;rster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
07:30

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion

Published on: May 10, 2018

9.4K
Mechanisms Underlying Gut Hormone Secretion Using the Isolated Perfused Rat Small Intestine
07:00

Mechanisms Underlying Gut Hormone Secretion Using the Isolated Perfused Rat Small Intestine

Published on: February 26, 2019

9.6K

Related Experiment Videos

Last Updated: Sep 8, 2025

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate
05:58

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate

Published on: June 25, 2019

7.6K
Homogeneous Time-resolved F&#246;rster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
07:30

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion

Published on: May 10, 2018

9.4K
Mechanisms Underlying Gut Hormone Secretion Using the Isolated Perfused Rat Small Intestine
07:00

Mechanisms Underlying Gut Hormone Secretion Using the Isolated Perfused Rat Small Intestine

Published on: February 26, 2019

9.6K

Area of Science:

  • Endocrinology
  • Molecular Pharmacology
  • G Protein-Coupled Receptor (GPCR) signaling

Background:

  • Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective for diabetes and obesity but cause side effects.
  • Receptor activity-modifying proteins (RAMPs) can modulate GPCR signaling and expression, offering a strategy to mitigate unwanted effects.
  • Understanding GLP-1R interactions with RAMPs is crucial for developing safer and more effective therapeutics.

Purpose of the Study:

  • To investigate the interaction between GLP-1R and Receptor activity-modifying protein 3 (RAMP3).
  • To determine how RAMP3 binding affects GLP-1R signaling pathways and functional outcomes.
  • To explore the therapeutic potential of the GLP-1R-RAMP3 complex for metabolic diseases.

Main Methods:

  • Co-immunoprecipitation assays to confirm GLP-1R and RAMP3 interaction.
  • Cell-based assays measuring calcium (Ca2+) mobilization and cyclic AMP (cAMP) production.
  • Analysis of G protein coupling (Gαs, Gαq, Gαi) upon GLP-1 stimulation in cells with varying RAMP3 expression.
  • In vivo studies using RAMP3 knockout mice to assess glucose and insulin tolerance.

Main Results:

  • GLP-1R forms a functional heterodimer with RAMP3 at the cell surface.
  • RAMP3 expression shifts GLP-1R signaling from canonical cAMP production towards Ca2+ mobilization and Gαq/Gαi coupling.
  • Overexpression of RAMP3 enhances GLP-1-mediated glucose-stimulated insulin secretion, while RAMP3 knockout mice show impaired glucose and insulin tolerance.

Conclusions:

  • RAMP3 acts as a crucial modulator of GLP-1R signaling, biasing its activity towards insulin secretion.
  • The GLP-1R-RAMP3 complex represents a promising therapeutic target for improving glycemic control with potentially reduced side effects.
  • These findings provide a basis for designing novel GLP-1R-targeting drugs by considering RAMP interactions.