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

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
Spare Receptors01:30

Spare Receptors

3.8K
Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
3.8K
Insulin: Biosynthesis, Chemistry, and Preparation01:25

Insulin: Biosynthesis, Chemistry, and Preparation

570
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
570
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
The Two-State Receptor Model01:29

The Two-State Receptor Model

2.5K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
2.5K
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

13.9K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
13.9K

You might also read

Related Articles

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

Sort by
Same author

Structure of α-Synuclein Bound to Polystyrene Surfaces Probed by Experimental and Theoretical Sum Frequency Generation Spectroscopy.

Langmuir : the ACS journal of surfaces and colloids·2026
Same author

Derivatization of Bufadienolides at Carbon-3 of the Steroid Core and Their Consequences for the Interaction with Na<sup>+</sup>,K<sup>+</sup>-ATPase.

International journal of molecular sciences·2025
Same author

Dynamics and structural features of the eEF1A1 and eEF1A2 paralogs.

Nucleic acids research·2025
Same author

Pathological Folding of α-Synuclein on Polystyrene Nanoplastic Revealed by Sum Frequency Scattering and 2D Infrared Spectroscopy.

The journal of physical chemistry letters·2025
Same author

Transmembrane domain interactions underlie NSG1 regulation of sortilin ectodomain shedding.

The Journal of biological chemistry·2025
Same author

The Martini 3 Lipidome: Expanded and Refined Parameters Improve Lipid Phase Behavior.

ACS central science·2025

Related Experiment Video

Updated: Sep 20, 2025

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

Exploring insulin-receptor dynamics: Stability and binding mechanisms.

Amanda D Stange1, Lorena Zuzic1, Birgit Schiøtt1

  • 1Department of Chemistry, Aarhus University, Aarhus, Denmark.

Structure (London, England : 1993)
|May 27, 2025
PubMed
Summary

Insulin binding to the insulin receptor (IR) triggers conformational changes. A new "ladder-climbing" model reveals how insulin moves between binding sites to activate the IR.

Keywords:
Insulin-binding hybrid sitesactivation mechanisminsulininsulin receptorinsulin-binding site 1insulin-binding site 2molecular dynamics simulations

More Related Videos

An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions
08:40

An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions

Published on: March 14, 2016

19.3K
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

Related Experiment Videos

Last Updated: Sep 20, 2025

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
An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions
08:40

An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions

Published on: March 14, 2016

19.3K
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

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Structural Biology

Background:

  • Insulin receptor (IR) activation involves significant conformational changes upon insulin binding.
  • Existing structural data offers limited insight into the dynamic sequence of IR activation events.
  • Understanding IR activation dynamics is crucial for metabolic research.

Purpose of the Study:

  • To investigate the dynamic process of insulin receptor activation using molecular dynamics simulations.
  • To elucidate the sequential events and conformational changes during IR activation by insulin.
  • To propose a novel mechanism for insulin-induced IR activation.

Main Methods:

  • Employed molecular dynamics (MD) simulations.
  • Utilized experimentally solved structures of IR-insulin complexes under physiological conditions.
  • Analyzed conformational changes and insulin binding site dynamics.

Main Results:

  • Observed insulin binding to hybrid sites induced opening of binding site 1.
  • Site 1-bound insulin promoted α-helix extension in the C-terminus of the α chain (αCT).
  • Demonstrated increased inter-domain stabilization mediated by insulin binding.

Conclusions:

  • Propose a novel 'ladder-climbing' mechanism for insulin-induced IR activation.
  • Insulin gradually migrates from site 2 to site 1, inducing controlled conformational changes.
  • This mechanism provides new insights into the dynamic regulation of insulin signaling.