Related Experiment Video

Updated: Nov 5, 2025

Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides
09:54

Synthesis and Characterization of 1,2-Dithiolane Modified Self-Assembling Peptides

Published on: August 20, 2018

7.5K

Thermo-Responsive self-assembly of a dual glucagon-like peptide and glucagon receptor agonist

Sonja Kinna1, Myriam M Ouberaï1, Silvia Sonzini2

  • 1Nanoscience Centre, Department of Engineering, University of Cambridge, Cambridge CB30FF, UK.

International Journal of Pharmaceutics
|May 20, 2021
PubMed

Insights

Oxyntomodulin (Oxm) self-assembles into amyloid-like nanofibrils, extending its therapeutic potential for obesity and diabetes. These Oxm fibrils exhibit unique temperature-dependent assembly kinetics, optimal at room temperature.

Area of Science:

  • Biochemistry
  • Materials Science
  • Endocrinology

Background:

  • Oxyntomodulin (Oxm) is a peptide hormone with potential for treating obesity and type 2 diabetes.
  • Pharmaceutical application is limited by rapid in vivo clearance and instability.
  • Previous work demonstrated Oxm self-assembly into amyloid-like nanofibrils for sustained release.

Purpose of the Study:

  • To investigate the fibril elongation kinetics and thermodynamics of Oxyntomodulin (Oxm).
  • To elucidate the structural characteristics of Oxm fibrils using advanced imaging and spectroscopic techniques.
  • To develop a thermodynamic model explaining Oxm self-assembly and disassembly.

Main Methods:

  • Cryo-electron microscopy (Cryo-EM) for structural analysis.
  • Spectroscopic methods to study fibril formation and kinetics.
  • Kinetic and thermodynamic analysis of Oxm fibril elongation.

Main Results:

  • Oxm fibril elongation exhibits a unique low-temperature optimum, with maximal rates at room temperature (25°C).
  • Association rates at 25°C were 2-3 times higher than at temperatures ≥37°C or ≤20°C.
  • Cryo-EM revealed Oxm fibrils possess a double-layered, triangular cross-section with arch-shaped monomers.

Conclusions:

  • Oxm nanofibrils offer a promising strategy for extending the half-life of Oxm for therapeutic applications.
  • The unique temperature-dependent kinetics of Oxm self-assembly are linked to its specific monomeric structure and thermodynamic properties.
  • Understanding these self-assembly properties is crucial for designing effective Oxm-based therapeutics for metabolic disorders.
Keywords:
Depot formulationGLP-1GlucagonOxyntomodulinSelf-assembly

More Related Videos

Author Spotlight: Improving the Production of Self-Assembling Fibers and Peptide Hydrogels for Superior Biocompatibility05:24

Author Spotlight: Improving the Production of Self-Assembling Fibers and Peptide Hydrogels for Superior Biocompatibility

Published on: September 6, 2024

1.5K
Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides07:26

Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides

Published on: November 21, 2013

13.1K

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...
513
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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...
6.2K
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
6.1K
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

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...
1.9K
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.
Insulin and C-peptide are...
1.6K
Insulin: Biosynthesis, Chemistry, and Preparation01:25

Insulin: Biosynthesis, Chemistry, and Preparation

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...
735