Related Experiment Video
Updated: Sep 8, 2025
08:04
Author Spotlight: Investigating Islet Abnormalities and Function with a Pseudoislet Protocol
Published on: November 3, 2023
2.1K
Glucagon and GLP-1 Accelerate Pseudo-Islet Assembly and Unmask Sex-Specific Islet Fragmentation Dynamics
Biorxiv : the Preprint Server for Biology
|August 20, 2025
Summary
Glucagon (GCG) and glucagon-like peptide-1 (GLP-1) influence human islet cell aggregation and structural integrity. These hormones promote pseudo-islet formation and affect native islet fragmentation in a sex-specific manner, impacting diabetes research.
Area of Science:
- Endocrinology and Metabolism
- Cell Biology and Tissue Engineering
Background:
- Pancreatic hormones like glucagon (GCG) and glucagon-like peptide-1 (GLP-1) are crucial for blood glucose regulation.
- Their roles in maintaining and inducing cell aggregation in culture, particularly for human islets, are not fully understood.
- Understanding islet cell behavior in culture is vital for diabetes research and therapeutic development.
Purpose of the Study:
- To investigate the effects of GCG and GLP-1 on the formation and integrity of human islet clusters in culture.
- To establish a human pseudo-islet platform for studying islet morphogenesis, architecture, and intercellular signaling.
- To assess the influence of cellular composition and donor sex on hormone-mediated effects on islet structure.
Main Methods:
- Human islets were dissociated and sorted into pure α-, β-, and δ-cell populations using fluorescence-activated cell sorting (FACS).
- Sorted cells were co-cultured with mouse endothelial MS1 cells to generate pseudo-islets.
- Hormonal supplementation with GCG or GLP-1 was administered during culture; native islets were also treated.
Main Results:
- Hormone-treated pseudo-islets formed faster, with effects dependent on cellular composition and donor sex.
- Native islets treated with hormones showed accelerated fragmentation in female donors but attenuated fragmentation in male donors.
- Pseudo-islet maturation versus fragmentation was primarily determined by cellular composition, with donor sex as a secondary factor.
Conclusions:
- GCG and GLP-1 enhance pseudo-islet formation and modulate the structural integrity of native human islets.
- These hormonal effects are sex-specific, influencing islet behavior differently in male and female donors.
- The study provides methodological guidelines for human pseudo-islet generation, offering a framework for diabetes research and optimizing experimental design.
Related Concept Videos
01:27Glucose 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...
Insulin and C-peptide are...
1.4K
01:24Glucagon-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...
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
01:05Insulin Secretory Vesicles
5.4K
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...
5.4K
01:16Hormones 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...
In addition to accelerating glucose uptake and utilization, insulin has...
4.0K
01:23Dipeptidyl 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
01:16Cells and Secretions of the Pancreas
2.9K
The pancreas, a vital organ within the abdominal cavity, plays dual roles in the digestive and endocrine systems, collaborating with exocrine and endocrine cells to maintain optimal digestion and blood sugar levels.
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
2.9K