13 - Hormones of the Pancreas Flashcards
Describe the importance of C peptide
There is a 1 to 1 ratio of endogenous insulin to C peptide (synthetic insulin does not)
In type 1 diabetes, you can tell how much insulin the own body is creating, so you can test C peptide
Can the body store insulin?
Yes ***
- The cells in the pancreas can secrete a lot of insulin when needed
- The stores of insulin will then be gone
- They have to make new insulin for the next meal – takes 30 or 60 minutes to produce and store insulin
- This means that sometimes it will be in a bi-phasic system… Production of insulin then secretion of insulin
What is the function of a pre-sequence which is attached to the insulin peptide?
Pre-sequence – connects the peptide to the ER, it will then come off
What needs to happen to proinsulin at the ER?
Needs to fold
Then it can go to the Golgi where A and B chains will be connected
Then the molecule is secreted as insulin
Describe the processing of A and B chains
Formation of insulin from proinsulin precursor assures that A and B chain are always present in equal amounts
What is familial hyperproinsulinemia?
- Defects in insulin processing due to mutations in insulin gene
- Affects how the insulin is cleaved
- If you don’t cleave the pro-insulin, you’re secreting pro-insulin not insulin
The pro-insulin does a good job of acting like insulin
What will you see in a patient with familial hyperproinsulinemia?
- High proinsulin levels in the blood
- Normal glucose metabolism because pro-insulin acts a lot like insulin
What cell in the islet of the pancreas makes the “players” of insulin release?
Beta cells - insulin secreting cells
What two organs in the body IMMEDIATELY respond to glucose?
- Liver
- Pancreas
This is because they respond to the glucose itself. All other tissues rely on insulin signaling in order to respond to increased glucose levels
If you want to increase the body’s consumption of glucose, what do you need?
Insulin
What effect does glucose have on the beta cells of the pancreas?
- Inhibition of potassium channels and opening of calcium channels
- Calcium will rush into the cell (INFLUX OF CA++)
- Cells respond to this influx of calcium by moving insulin vesicles to the surface of the cell and releasing the contents
- Glucose leads an increase in ATP in the pancreas
What are the two “phases” of insulin secretion?
- Producing insulin to “stock” the vesicles
- Secreting stocked insulin from the vesicles
How does glucose increase insulin production (the first step)?
- Insulin gene increases when glucose is around, leading to mRNA, ribosomes and ER allow for elongation and production of insulin
- Every step along the way responds to glucose in the beta cell of islet cells in the pancreas to produce insulin
Where are insulin receptors found in the body?
Literally everywhere!
What subunits do you find in insulin receptors?
A tetrameric complex
- Two alpha subunits
- Two beta subunits
What happens when insulin binds to an insulin receptor?
A phosphorylation cascade
- First the beta subunits will be autophosphorylated
- This stimulates tyrosine kinase activity of the receptor
- IRS2 is then phosphorylated, which is insulin receptor substrate 1
- Most of the insulin effects require Ser/Thr phosphorylation
Basically, there is a phosphorylation cascade following the binding of insulin to its receptor
What is the paradox of insulin binding?
Receptor activation leads to phosphorylation of signaling proteins and DEphosphorylation of metabolic enzymes
What are the three categories of responses to insulin?
1 - Glucose metabolism and glycogen/lipid synthesis
2 - Protein synthesis
3 - Cell proliferation
What is GLUT 4?
Most tissues in the body have GLUT4, which is a transporter that is translocated to the plasma membrane to facilitate the uptake of glucose
