Related Experiment Video
Updated: Jul 11, 2026
09:41
Confocal Imaging of Neuropeptide Y-pHluorin: A Technique to Visualize Insulin Granule Exocytosis in Intact Murine and Human Islets
Published on: September 13, 2017
Dynamin is functionally coupled to insulin granule exocytosis.
Le Min1, Yuk M Leung2, Alejandra Tomas3
1Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11794.
The Journal of Biological Chemistry
|September 13, 2007
Summary
This study reveals a selective kiss and run mechanism for insulin release from beta-cells, indicating a link between endocytosis and exocytosis in insulin secretion regulation.
Area of Science:
- Cell Biology
- Endocrinology
- Molecular Biology
Background:
- Insulin secretion is crucial for glucose homeostasis.
- The precise mechanisms of insulin granule exocytosis and subsequent endocytosis remain under investigation.
- Dynamin's role in beta-cell secretion is not fully elucidated.
Purpose of the Study:
- To investigate the role of dynamin in insulin granule trafficking and secretion.
- To explore the mechanism of insulin release, specifically examining the 'kiss and run' hypothesis.
- To determine the coupling between endocytosis and exocytosis in beta-cells.
Main Methods:
- Utilized Min6B1 beta-cells expressing phogrin-green fluorescent protein and human growth hormone.
- Employed a dominant-interfering dynamin mutant (Dyn/K44A) and small interference RNA (siRNA) for dynamin knockdown.
- Assessed transferrin receptor endocytosis, phogrin localization, and cell surface capacitance changes.
- Measured human growth hormone release in response to various secretagogues and depolarization.
Main Results:
- Phogrin-green fluorescent protein localized with insulin but did not translocate to the plasma membrane upon glucose stimulation.
- Dominant-interfering dynamin mutant inhibited human growth hormone release and cell surface capacitance increase, but not phogrin localization.
- Dynamin knockdown significantly inhibited glucose-stimulated insulin secretion.
- Data suggest a selective 'kiss and run' mechanism for insulin release.
Conclusions:
- Insulin release involves a selective 'kiss and run' process, distinct from full granule fusion.
- Dynamin plays a critical role in regulating insulin secretion, likely by coupling exocytosis and endocytosis.
- These findings provide new insights into the complex regulation of beta-cell function and insulin secretion.
Related Concept Videos
01:05Insulin 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...
01:33Overview of Secretory Vesicles
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
01:32Pinching-off of Coated Vesicles
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
01:28Insulin: 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 this inhibition is released...
01:27Glucose 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 co-secreted in...
Insulin and C-peptide are co-secreted in...
01:25Insulin: 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 primarily uses...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...