Endocrine Pancreas Flashcards
What are the endocrine cells of the pancreas arranged into?
Islets of Langerhans (clusters)
What type of cells exist in the islets of Langerhans?
alpha cells
beta cells
delta cells
F cells
What do alpha cells release in the endocrine pancreas?
Glucagon
What do beta cells release in the endocrine pancreas?
Insulin and C peptide
What is C peptide used for?
To measure function of beta cells and of endogenous insulin secretion
What do delta cells release in the endocrine pancreas?
Somatostatin
What do F cells release in the endocrine pancreas?
Pancreatic polypeptide
Where are the alpha cells located in the islets?
Periphery
Where are the beta cells located in the islets?
Central
Where are delta cells located in the islets?
Interspersed between alpha and beta cells
What is the signal the F cells send?
Satiety (feeling full)
What stimuli causes beta cells to release insulin?
GLUCOSE ingestion
What is the majority cell in the endocrine pancreas (60%)?
Beta cells
How do cells within the islet communicate with each other?
Gap junctions based on ion concentration changes
Describe the blood flow to the islets of Langerhans in the pancreas
- Blood flows into the central region first, contacting the beta cells
- Then the venous blood flows from the central region to the peripheral region, contacting the alpha and delta cells
- This brings insulin (from beta cells) to the alpha and delta cells which inhibits the alpha cells from releasing its product (glucagon)
What is the order of how insulin is made?
- Preproinsuliln
- Proinsulin - packaged into vesicles and cleaved by proteases
- Insulin and C peptide
What is the function of the endocrine pancreas cells?
Regulate lipid, carb, and AA metabolism
What receptor is used to bring glucose into a beta cell?
GLUT - 2
What are the steps to insulin and C peptide release from a beta cell?
- Glucose enters cell via GLUT-2
- Glucose is phosphorylated/oxidized to generate ATP
- Rising ATP levels CLOSES K+ channel so K+ remains in the cell
- This moves the cell towards more depolarization and opens Ca++ channels
- Ca++ allows the vesicles containing insulin and C peptide granules to be released out of the cell
What is the name of the receptor that closes the ATP-dependent K+ channels and what does it ultimately result in?
Sulfonylurea receptor = INCREASES insulin secretion
Describe the insulin release based on time after eating
- Initial spike of insulin release within MINUTES after eating
- Then it returns to normal but slowly INCREASES about an hour later
Describe the overall summary of Type 2 diabetes
- Glucose levels are normal or elevated
- Pancreas beta cells secrete MORE insulin
- Peripheral tissues (adipose, skeletal muscle, liver) do NOT respond!
“insulin resistance”
When does insulin resistance begin to occur with type 2 diabetes?
Very early in disease progression
What receptor is used to bring glucose into peripheral tissues?
GLUT-4
Describe how glucose is supposed to be brought into peripheral tissues (adipose, skeletal muscle, liver)?
- Insulin binds to receptor
- MAP kinases mediate downstream pathways
- Translocation of vesicle containing GLUT-4 sent to plasma membrane
= Glucose enters cell via facilitated diffusion
- Translocation of vesicle containing GLUT-4 sent to plasma membrane
What are some stimuli that activate insulin secretion?
Increased glucose Glucagon Ach CCK Cortisol K+ Sulfonylruea drugs
What are some stimuli that inhibit insulin secretion?
Somatostatin Decreased glucose Fasting Exercise NE
What does insulin promote peripheral tissues to do?
Uptake/store glucose
Insulin also promotes K+ _____, which causes _____
Uptake
This causes decreased K+ levels in the blood
What can stimulate glucose uptake independent of insulin?
Muscle contraction
What is the role of glucagon?
To INCREASE glucose levels
What does glucagon promote peripheral tissues to do?
Glucose formation
What are the major activators and inhibitors of glucagon release?
(+) = decreased glucose levels (-) = insulin
Which type of diabetes mellitus has more of a genetic component that predisposes them to the condition?
Type 2
What are some factors that lead to the development of Type 2 DM?
Excessive caloric intake Sedentary behavior Genetic component Ethnicity - african american Adipose tissue dysfunction and chronic inflammation
Steps to insulin resistance and Type 2 DM
- Insulin release
- Hyperinsulinemia - normal glucose levels but takes more insulin to get them there
- Postprandial hyperglycemia
- Disrupted response to oral glucose tolerance test
- Chronic elevated insulin levels
- Mild to moderate elevated glucose levels
- Hyperglycemia
How long can it take to develop Type 2 DM?
5-30 years
Type 1 diabetes mellitus
Autoimmune destruction of beta cells = NO insulin or C peptide release!
Signs of Type 1 diabetes mellitus
Childhood onset Hyperglycemia Diabetic ketoacidosis Hyperkalemia Polydipsia (thirst)
