The Blue Line shows insulin synthesis and release.
This is Adenylyl Cyclase (AC).
Once the G alpha protein is activated in the Green Line, activates adenylyl cyclase (AC).
AC then converts ATP, produced earlier from glucose in the Orange Line, into cAMP.
This is cAMP.
cAMP is a small signaling molecule, a secondary messenger, that helps pass messages inside the cell to trigger important responses. The Blue Line shows one of the many pathways that cAMP triggers.
Rising cAMP levels activate a protein called Protein Kinase A (PKA).
PKA is an enzyme that activates other proteins by adding phosphate groups to them.
PKA moves into the nucleus.
The nucleus is where DNA is stored and gene expression begins. PKA starts the process of transcription, which is turning the DNA gene into mRNA.
The nucleus activates proteins, including transcription factors like CREB and PDX-1. Transcription factors help control which genes get turned on.
They bind to the gene’s promoter region and activate the insulin gene transcription.
This is Insulin mRNA.
Insulin mRNA contains instructions for how to make the insulin peptide. It carries this information from the nucleus into the cytoplasm, where protein production occurs.
This is the Ribosome.
Ribosomes are the cell’s protein builders. They read the mRNA instructions and make the insulin protein.
This is the Endoplasmic Reticulum.
The ER is the first site of protein synthesis. The ER is covered in ribosomes and helps fold and modify new proteins so they work properly.
In the ER, the ribosome reads the insulin mRNA and builds a protein called preproinsulin in a process called translation. Preproinsulin is a single stranded precursor of insulin with a signal peptide that tells the cell to send it to the rough ER. Preproinsulin is then trimmed (the signal peptide is removed) and folded into proinsulin.
This is the Golgi Apparatus.
The Golgi is the cell’s packing and shipping center. It prepares proteins for transport and final modifications. In the Golgi, Proinsulin is packaged into transport vesicles. Special enzymes cut it, remove the C-peptide, and turn it into mature insulin (A and B chains held together by disulfide bonds).
Insulin is then stored in secretory granules. Inside the Golgi and insulin vesicles, insulin molecules crystallize.
This is an Insulin Vesicle.
These vesicles are small bubbles that carry insulin around the cell. They store insulin until the cell gets a signal (like calcium) to release it.
Mature insulin starts off as a monomer.
When 2 monomers join together, it forms a dimer.
When 3 dimers join together, it forms a hexamer.
When multiple hexamers join together, a crystal is formed.
The crystalline hexameric form of insulin is stable, compact, and helps protect insulin from degradation.
Here is a video showing the process of insulin crystal formation in the pancreatic beta cell.
The release of insulin from the secretory granules is driven by membrane depolarization (rising ATP levels). ATP drives the KATP channel to open and close. When the KATP channel closes, there is an influx of Ca2+ into the cell.
The instrument for insulin release is called the SNARE complex. 1 part of the complex is located on the plasma membrane of the cell and the other part is located on the vesicle membrane (where insulin is stored).
When Ca2+ is released, the 2 parts of the SNARE complex start to entangle in each other. They pull the two lipid membranes close together until eventually they fuse.
When the membranes fuse, they create a channel between the vesicle lumen and the extracellular space. The insulin inside the vesicle is released through the channel and into the bloodstream. The insulin crystals dissolve and insulin is released mostly as monomers, an active form of insulin that can move into the bloodstream and bind to insulin receptors.
Here is a video showing this process of insulin’s release from the secretory granule into the bloodstream.
Congratulations!
You learned how insulin is secreted and released from the pancreatic beta cell.
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