Pancreas Flashcards
What are the major cells in the Islets of Langerhans?
Alpha Beta Delta PP Epsilon
What is the function of alpha cells?
Make glucagon
What is the function of beta cells?
Make insulin
What is the function of delta cells?
Make somatostatin (SS14)
What is the function of PP cells?
Secrete pancreatic polypeptide
What is the function of epsilon cells?
Make ghrelin
What is the major function of insulin?
Energy storage (anabolic hormone)
What is the major function of glucagon?
Energy mobilization (catabolic hormone)
Describe the arrangement of alpha and beta cells.
Beta cells clustered in “core”; other cells in “mantle.”
Alpha cells surround beta cells in a sandwich formation and the line the outer capillaries.
How does blood flow in the Islets of Langerhans?
Blood feeds the center of the Islet and then
flows outward
Describe the processing of insulin.
Insulin is released with C-peptide and the C chain is cleaved off which is necessary for insulin to bind to its receptor
What is the function of C-peptide?
C peptide has a long half life in the blood and is used to measure pancreatic function
How does glucose outside of the beta cell stimulate the initiation of insulin release?
Transported into cell by GLUT-2, which has LOW affinity for glucose. Only when glucose is high will it transport.
What happens to glucose once it is transported into the beta cell?
Glucose will be turned into G6P only when the glucose levels are high as glucokinase has a low affinity for glucose.
G6P will be metabolized and it will generate ATP.
What happens with increased ATP levels in the beta cell?
Increased ATP will cause the cell’s K+ channels to close and as a result, K+ will accumulate within the cell.
What is the function of sulfonylurea drugs?
They will also close the K+ channels in the beta cell, bypassing the glucose steps
What happens with increased K+ within the beta cell?
It will cause the cell to depolarize and Ca2+ channels to open.
What happens to the beta cell with the opening of the Ca2+ channels?
The Ca2+ influx will will cause the exocytosis of insulin vesicles
How do FFAs and AAs affect insulin release?
They will increase it as both can generate ATP within the beta cell as well
What is the biphasic insulin response following a meal?
1 - there is an initial insulin spike signaling the release of insulin that has already been docked at the membrane
2 - the rising slope after the drop signals newly synthesized insulin being released
What is the insulin receptor and how does it work?
It is a tyrosine kinase receptor and insulin binds receptor at alpha subunit and the beta subunit is autophosphorylated
What is the action of insulin in the muscle cell?
It allows for muscles to uptake glucose via GLUT4, otherwise, muscles cannot intake glucose.
What is the pathway for insulin action of the muscle cell?
- Autophosphorylation of receptor recruits IRSs (insulin receptor substrates).
- IRSs activate intracellular signaling cascades
RESULT: GLUT-4 inserted in membrane – glucose can enter cell
Which of the glucose transporters is glucose independent?
GLUT-1, 2, 3 are all insulin independent
What glucose transporter is glucose dependent?
GLUT-4 in muscle
What is the effect of insulin on the liver?
Promotes glycogen and TAG production Reduces glucose production/output
What is the effect of insulin on muscle?
Promotes glycogen and TG production and protein synthesis
What is the effect of insulin on fat?
Promotes TAG production, release of FFAs from chylomicrons, glycolysis
How is glucagon processed in the pancreatic alpha cell?
GRPP is cleaved from GLUC and is inactive
GLP-1 and 2 (Incretins) are not cleaved an inactive
GLUC is cleaved free and is active
How is glucagon processed in the intestinal L cell?
GRPP-GLUC is not cleaved and remains inactive as glicentin
The incretins GLP-1 and 2 are cleaved in the intestine and active.
What is the function of incretins?
They increase the amount of insulin released from the pancreas
When is glucagon released?
Major counterregulatory hormone to insulin – most things that stimulate insulin will inhibit glucagon.
Released in response to low blood glucose levels.
What effect do AAs have on glucagon release?
AAs stimulate release (protein meals)
What effect do catecholamines have on glucagon release?
Catecholamines stimulate release (exercise)
What is the effect of insulin on ketogenesis?
Insulin will inhibit ketogenesis
What is the function of somatostatin (SS14)?
Suppresses insulin release - used in clinic for management of insulin-producing tumors
What is the regulation of SS14?
Produced by delta cells in pancreatic islets
Stimulated by high fat, high carb meals.
Inhibited by insulin
What is the function of amylin?
Released with insulin from vesicles in beta cells
Synergistic with insulin in regulation of blood glucose
What is the function of ghrelin?
Stimulates food intake at level of hypothalamus
Stimulates GH release
Inverse correlation between circulating ghrelin and obesity
What are the main counter regulatory hormones to insulin?
Glucagon
Growth Hormone
Cortisol
Catecholamines
