Related Experiment Video
Updated: May 21, 2026
06:45
In Vivo Single-Molecule Tracking at the Drosophila Presynaptic Motor Nerve Terminal
Published on: January 14, 2018
Munc18-1 regulates first-phase insulin release by promoting granule docking to multiple syntaxin isoforms.
Eunjin Oh1, Michael A Kalwat, Min-Jung Kim
1Department of Pediatrics, Herman B. Wells Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
The Journal of Biological Chemistry
|June 12, 2012
Summary
Munc18-1 protein is crucial for first-phase insulin secretion in human islet beta cells. Its levels influence insulin granule docking, suggesting a novel role in diabetes.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Medicine
Background:
- Reduced Munc18-1 levels in human islet beta cells are linked to type 2 diabetes.
- The precise mechanism by which Munc18-1 regulates insulin secretion is not fully understood.
Purpose of the Study:
- To investigate the role of Munc18-1 in insulin secretion and granule dynamics.
- To elucidate the molecular interactions of Munc18-1 in beta cells.
Main Methods:
- Utilized Munc18-1(+/-) and beta-cell specific Munc18-1(-/-) knockout mice.
- Analyzed insulin secretion and insulin granule numbers at the plasma membrane in human islets with varying Munc18-1 levels.
- Examined SNARE complex formation and protein-protein interactions.
Main Results:
- Munc18-1 deficiency impaired first-phase insulin secretion and reduced pre-docked insulin granules.
- Elevated Munc18-1 potentiated first-phase insulin release and increased pre-docked granules.
- Munc18-1 indirectly facilitated syntaxin 4-mediated granule pre-docking, independent of direct SNARE complex binding.
Conclusions:
- Munc18-1 is essential for first-phase insulin secretion by regulating insulin granule pre-docking.
- Syntaxin 4 plays a key role in Munc18-1-mediated potentiation of insulin release.
- These findings reveal a novel indirect mechanism for Munc18-1 in supporting insulin exocytosis, relevant to type 2 diabetes.
More Related Videos
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...
01:28Insulin: 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...
01:26Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
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...