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

416
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...
416
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

256
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...
256
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
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

257
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...
257
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

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

Crediting and citing Indigenous Knowledges within research.

Bioscience·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 author

PLACENTAL AND FETAL RESPONSES TO ADRENOMEDULLIN DEFICIENCY IN THE RAT.

Biology of reproduction·2026
Same author

Evaluating the Diagnostic Performance of Clear Cell Likelihood Score in Predicting Clear Cell Renal Cell Carcinoma Among Patients Younger Than 50 Years.

JCO oncology practice·2026
Same journal

Wanted and unwanted modifications of mRNA, and their effect on gene expression and signaling.

The Journal of biological chemistry·2026
Same journal

TGF-β2 drives lipid droplet accumulation in chondrocytes through the TβRI/p-Smad3/Fabp5 axis.

The Journal of biological chemistry·2026
Same journal

Macrophage-specific targeting of histone demethylases with small-molecule inhibitors suppresses inflammatory response in vivo.

The Journal of biological chemistry·2026
Same journal

Substrate and target selectivity of 4'-fluoroadenosine against viral and host polymerases.

The Journal of biological chemistry·2026
Same journal

Correction: Characterization of Mast2 kinase defines structural features, regulation, and substrates.

The Journal of biological chemistry·2026
Same journal

Isotope-Edited ESEEM: A New Method for Probing Copper Binding Sites in Neurodegenerative Proteins.

The Journal of biological chemistry·2026
See all related articles

Related Experiment Video

Updated: Sep 10, 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, Cambridge, UK.

The Journal of Biological Chemistry
|August 20, 2025
PubMed
Summary
This summary is machine-generated.

Receptor activity-modifying protein 3 (RAMP3) modulates Glucagon-like peptide-1 receptor (GLP-1R) signaling, enhancing insulin secretion. This interaction may reduce side effects associated with current GLP-1R therapies for diabetes and obesity.

Keywords:
G protein–coupled receptorallosteric regulationcalcium intracellular releasediabetesinsulin secretionsecond messenger

More Related Videos

Homogeneous Time-resolved Förster 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 10, 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 Förster 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:

  • Pharmacology
  • Endocrinology
  • Molecular Biology

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 alter agonist binding and signaling, potentially mitigating unwanted effects.
  • RAMPs offer a strategy to develop more selective GLP-1R therapeutics.

Purpose of the Study:

  • To investigate the interaction between GLP-1R and RAMP3.
  • To determine how RAMP3 influences GLP-1R signaling pathways.
  • To assess the therapeutic potential of the GLP-1R-RAMP3 interaction for metabolic diseases.

Main Methods:

  • Co-immunoprecipitation to confirm GLP-1R and RAMP3 interaction.
  • Measurement of intracellular calcium (Ca2+) and cyclic adenosine monophosphate (cAMP) signaling.
  • Analysis of G protein coupling (Gαs, Gαq, Gαi) upon GLP-1R activation.
  • In vivo studies using RAMP3 knockout mice for glucose and insulin tolerance tests.

Main Results:

  • GLP-1R forms a functional heterodimer with RAMP3 at the cell surface.
  • RAMP3 expression shifts GLP-1R signaling from cAMP to Ca2+ mobilization.
  • RAMP3 enhances GLP-1-induced insulin secretion by altering G protein coupling.
  • Ramp3 knockout mice exhibit reduced sensitivity to GLP-1 in glucose and insulin tolerance tests.

Conclusions:

  • RAMP3 acts as a crucial modulator of GLP-1R function.
  • The GLP-1R-RAMP3 interaction presents a novel therapeutic target for improving metabolic control.
  • Understanding this interaction can guide the design of next-generation GLP-1R-based drugs with improved safety profiles.