Pancreas (L10) Flashcards
Endocrine pancreas
Three types of cells clustered into the “islets of Langerhans”
Endocrine pancreas
Three types of cells clustered into the “islets of Langerhans”
Histology of the endocrine pancreas
“cord” network surrounded by reticular fibers
How many islets of Langerhans are there in a typical human?
About 1 million
Beta cells: product and percentage
73-75%; secrete insulin
Alpha cells: product and percentage
18-20%: secrete glucagon
Delta cells: product and percentage
4-6%: secrete somatostatin
PP cells: product and percentage
Arrangement of alpha and beta cells
Alpha cells in the mantle surround beta cells in the core
Arrangement of alpha and beta cells
Alpha cells in the mantle surround beta cells in the core
Histology of the endocrine pancreas
“cord” network surrounded by reticular fibers
How many islets of Langerhans are there in a typical human?
About 1 million
Beta cells: product and percentage
73-75%; secrete insulin
Alpha cells: product and percentage
18-20%: secrete glucagon
Delta cells: product and percentage
4-6%: secrete somatostatin
What types of glucose receptors are present on beta cells?
GLUT2 receptors: low affinity, only active in high concentrations of glucose
Epsilon cells: product and percentage
Arrangement of alpha and beta cells
Alpha cells in the mantle surround beta cells in the core
How does blood flow in the islet?
From the center outward; venous blood rich in hormone
Minor pancreatic hormones
Ghrelin, somatostatin, amylin, pancreatic peptide
Half life of insulin
3-8 minutes
Incretins
Potentiate insulin release, but are still glucose dependent
What is C-peptide used for?
Can be measured as a good indicator of pancreatic function due to half life of 35 minutes
What is the C-chain necessary for?
Proper folding and disulfide linking of the alpha and beta chains
Insulin release in response to a meal
Amplitude and frequency of insulin release will continue to rise until glucose levels are normalized
Once inside the beta cell, what happens to glucose?
Phosphorylated by glucokinase
Describe what happens when insulin binds its receptor.
Insulin binds the alpha subunit and causes autophosphorylation of intracellular beta subunit, which phosphorylates IRSs and activates intracellular signaling cascades
Once G6P is created, what happens?
The G6P is metabolized and the increased ATP causes closing of potassium channels, which leads to depolarization of the cell
Main mediators of insulin’s effects
PI3K - metabolic effects
MAPK - mitogenic effects
Sulfonylurea drugs
There is a SUR binding unit on the potassium channels of beta cells, causing more cell depolarization and increased insulin release
Incretins
Potentiate insulin release, but are still glucose dependent
Catecholamines and insulin release
Inhibitory
Biphasic glucose release
5% of insulin vesicles are docked at the membrane and are released immediately. The other 95% are moved from inside the cell and take longer
What type of receptors are insulin receptors?
Tyrosine kinase receptors
Describe what happens when insulin binds its receptor.
Insulin binds the alpha subunit and causes autophosphorylation of intracellular beta subunit
What happens after downstream targets of IRSs are activated?
GLUT4 is inserted into the cell membrane and cell can take up glucose
Main mediators of insulin’s effects
PI3K - metabolic effects
MAPK - mitogenic effects
Physiologic effects of insulin on the liver
Promotes glycogen and triglyceride production; reduces glucose production/output
Physiologic effects of insulin on muscle
Promotes glycogen and triglyceride production, as well as protein synthesis
Stimulators of somatostatin release
High fat, high carb meals
Components of proglucagon
Glucagon-related peptide, glucagon, GLP-1 and GLP-2 (incretins)
Processing of proglucagon in the alpha cell
GRPP is cleaved and left as inactive peptide; GLP-1 and 2 remain linked and are also inactive
Processing of proglucagon in the intestine
GRPP stays linked to glucagon and they both remain inactive as glicentin. However, GLP-1 and 2 are cleaved and are active as potentiators of insulin release
What stimulates GLP release in the intestines?
Carbohydrates
Stimulators of glucagon release
Low blood glucose levels, protein ingestion, and catecholamines
Insulin’s effect on the bifunctional enzyme
Insulin dephosphorylates the portion of the enzyme conferring kinase activity, promoting glycolysis
Glucagon’s effect on the bifunctional enzyme
Glucagon phosphorylates the portion of the enzyme conferring phosphatase activity, promoting gluconeogenesis
Somatostatin and insulin
Inhibit each other; somatostatin treatment is used in the case of insulin-releasing tumors
What does amylin do?
It is released with insulin to synergize in the regulation of blood glucose
Pathology of amylin
Increased in obesity and hypertension, which could aid in destruction of beta cells by forming amyloid
Stimulatory functions of ghrelin
Stimulates food intake at level of hypothalamus
Stimulates GH release
Ghrelin and obesity
Inverse relationship between the two
Paracrine actions of ghrelin
Inhibits insulin release via activation of potassium channels
Decreases intracellular calcium
Where is ghrelin produced and released?
In the stomach and newly described epsilon cells of the islets of Langerhans
Four counterregulatory hormones of insulin
Glucagon, GH, cortisol, and catecholamines
GH without insulin
Has the glucose mobilization effects, but no IGF-1 is released and no cell proliferation effects take place. GH is elevated due to lack of negative feedback
Growth hormone and cortisol as counterregulators of insulin
Stimulate lipolysis and gluconeogenesis; delayed release (6 hours) to protect against prolonged starvation
