L76: Pancreas

Question 1

Describe the sequence of ducts with the gall bladder, liver, and pancreas

Answer 1

Cystic duct + common hepatic duct -> common bile duct +pancreatic duct -> greater duodenal papill-> duodenum

Question 2

What is the the exocrine pancreas?

Answer 2

Makes up majority of cells in the pancreas

Acinar cells: secrete digestive enzymes into pancreatic duct

Question 3

What is the endocrine pancreas?

Answer 3

3 major cell types making up islets of langerhans (alpha, beta, delta)

Question 4

What do the ductal cells in the exocrine pancreas do?

Answer 4

secretes mucous and bicarb to the pancreatic enzyme mixture from acinar cells

Question 5

What which cells of the endocrine pancreas regulate glucose metabolism?

Answer 5

Alpha: glucagon
Beta: inuslin

Question 6

What do the PP and delta cells do?

Answer 6

produced pancreatic polypeptide and somatostatin

Question 7

What does pancreatic polypeptide do?

Answer 7

Inhibit acinar cells via paracrine action

Question 8

What do epsilon cells secrete?

Answer 8

ghrelin

Question 9

How is the blood flow arranged in the endocrine pancreas?

Answer 9

Blood flow is from arteriole into center of islet outward to the venule

Insulin rich blood flows from the center into the periphery of the islet

Question 10

How are beta and alpha cells organized in the islets?

Answer 10

Beta cells clustered in core -> alpha cells surround beta cells in a sandwich formation -> allows paracrine effects between them

Question 11

What does insulin do?

Answer 11

Anabolic hormone: energy storage

Question 12

What does glucagon do?

Answer 12

Catabolic: energy mobilization

Question 13

What are the minor hormones in the pancreas?

Answer 13

Somatostatin
Amylin
Pancreatic polypeptide
Ghrelin (hunger hormone)

Question 14

How i insulin synthesized?

Answer 14

Insulin+ C peptide released together as proinsulin -> cleavage of C peptide exposes end of insulin chain to interact wiht receptor

Insuline and C peptide are packaged together in storage vesicles

Question 15

Why is the C peptide important for insulin biosynthesis?

Answer 15

C peptide is critical for proper folding and formaiton of disulfide bonds between the alpha and beta chain

Question 16

How can C peptide be used clinically?

Answer 16

Can indicate pancreatic function status due to long half life (35 mins) compared to insulin (3-8 minutes)

Question 17

How is insulin released from the pancreatic beta cell?

Answer 17

Glucose outside of the beta cell transported in by GLUT-2 (only when glucose is HIGH) -> glucose phosphorylated by glucokinase (glucose sensor) -> G6P-> increased ATP via glucose metabolism -> closes K+ channels w/ SUR subunits -> cell depolarizes -> open Ca2+ channels -> vesicle exocytosis

Question 18

What do sulfonylurea drugs do?

Answer 18

Closes K+ channels to cause depolarization of the cell -> and thus cause insulin release

Question 19

How do FFAs and amino acids modulate insulin release from beta cells?

Answer 19

Increase ATP levels via oxidation and thus close K+ channels

Question 20

What do incretins (GLP-1) do?

Answer 20

potentiate insulin released

STILL NEEDS GLUCOSE

Question 21

How do catecholeamines affect insulin release?

Answer 21

Inhibit it

Question 22

In what behavior is insulin released in response to glucose?

Answer 22

Biphasic:
5% of vesicles available for immediate release at membrane
95% stored or newly synthesized insulin

Initial spike-> followed by gradual increase in 2nd phase

Question 23

What kind of receptors does insulin bind?

Answer 23

Membrane receptor tyrosine kinases at hte alpha subunit

Question 24

What does insulin binding to its receptor do?

Answer 24

Binds at alpha subunit on EC space -> autophosphorylation of intracellular beta subunit (tyrosine kinase domains)

Question 25

What are insulin's actions on muscle cell?

Answer 25

Glucose cannot enter cell without insulin Insulin binds- > autophosphorylation of receptors -> recruit IRSs -> activate intracellular signaling cascades -> promote GLUT-4 insertion into membrane -> allows glucose to enter cell

Question 26

What is IRS(insulin receptor substrate)?

Answer 26

Scaffolding protein that recruits intracellular signaling components like PI3K and MAPK

Question 27

Which GLUT transporters are insulin dependent?

Answer 27

GLUT-4 (Skeletal muscle, fat)

Question 28

Which GLUT transporters are insuin INdependent?

Answer 28

GLUT-1(brain, vasculature, erythrocytes, skeletal msucle, fat, heart) GLUT-2(Pancreatic beta cells, liver, intestine, kidney) GLUT-3(neurons)

Question 29

What effects does insulin have on the liver?

Answer 29

promote glycogen and TG produciton | REduce glucose produciton/output

Question 30

What effect does insulin have on muscle?

Answer 30

promote glycogen and TG production, and protein synthesis

Question 31

What effect does insulin have on fat?

Answer 31

Promote TG production, release FFAs from chylomicrons, glycolysis, inhibit lipolysis

Question 32

How is glucagon synthesized and processed?

Answer 32

Preproglucagon (SP-GRPP-GLUC-GLP-1-GLP-2) Pancreatic Alpha Cells: GRPP cleaved from Glucagon -> secreted as inactive peptide -> GLP-1 and GLP-2 remain linked(inactive) => GRPP(inactive) + GLUC + GLP-1/GLP-2(inative) Intestinal L Cells: GRPP linked to glucagon (glicentin) -> inactive -> GLP-1 and GLP-2 cleaved -> active INCRETINS => Glicentin + GLP-1 + GLP-2

Question 33

What do incretins do?

Answer 33

Potentiate insulin release from pancreatic beta cells | Stimulated by carbohydrates in intestines

Question 34

What is the stimulus for glucagon release?

Answer 34

low blood glucose Amino acidss (protein meal) Catecholeamines/Exercise

Question 35

Does glucagon exhibit biphasic release like insulin?

Answer 35

NO | Glucagon levels fall at a constant rate

Question 36

How do insulin and glucagon work together?

Answer 36

Insulin: dephosphorylate kinase activity enzyme-> phosphorylation activity -> promotes glycolysis Glucagon: phosphorylates phosphatase activity enzyme-> desphosphorylation activity -> promote gluconeogenesis

Question 37

What are the main targets of glucagon?

Answer 37

Liver and Adipose: promote energy mobilization | Opposite of insulin

Question 38

Where are somatostatins produced and what stimulates their release?

Answer 38

Delta Cells Stimulated by high fat, high carb diets Inhibited by insulin

Question 39

What does somatostatin do?

Answer 39

Inhibit insulin released | Can be used clinically to manage insulin producing tumors

Question 40

What does Amylin do?

Answer 40

Released with insulin from beta cell vesicles and works synergistically with insulin

Question 41

What causes an increase in amylin?

Answer 41

Obesity, HTN

Question 42

What does amyloid formation lead to in the pancreas?

Answer 42

beta cell destruction

Question 43

Where is Ghrelin produced?

Answer 43

Stomach (most) | Epsilon cells in islet

Question 44

What does Ghreln do/?

Answer 44

Stimulate food intake at hypothalamus Stimulate GH release Inhibit insulin release from beta cells by activating K+ channels and decreasing intracellular calcium release

Question 45

How is ghrelin related to obesity?

Answer 45

Inversely related: obesity -> lower ghrelin

Question 46

What are counter regulatory hormones to insulin?

Answer 46

Glucagon: primary GH + Cortisol: promote gluconeogenesis and lipolysis Catecholeamines: increased with exercise and stress; stimulates glucagon release and inhibit insulin release

Question 47

How are insulin and GH related?

Answer 47

Absent insulin + GH increased -> cannot stimulate hepatic IGF-1 => direct GH effects on glucose mobilizaiton but no cellular proliferation effects of IGF-1 Also get no neg feedback to GH (NO IGF-1)