Endocrine Pancreas

Question 1

What two substances work together to regulate blood glucose after a meal and during fasting?

Answer 1

insulin and glucagon

Question 2

What part of the endocrine pancreas is responsible for synthesizing hormones?

Answer 2

pancreatic islets of langerhans

Question 3

What cells of the endocrine pancreas produce insulin?

Answer 3

beta cells

Question 4

Where are beta cells located?

Answer 4

most are in center of islet

Question 5

What cells of the endocrine pancreas produce glucagon?

Answer 5

alpha cells

Question 6

Where are alpha cells located?

Answer 6

most are around outer rim of islet

Question 7

What cells of the endocrine pancreas produce somatostatin?

Answer 7

delta cells

Question 8

Where are delta cells located?

Answer 8

interspersed around beta and alpha cells

Question 9

What connects alpha cells to each other, beta cells to each other, and alpha cells to beta cells?

Answer 9

gap junctions

Question 10

What allows for communication among islet cells?

Answer 10

• gap junctions
• blood supply
• innervation by adrenergic, cholinergic, and peptidergic neurons

Question 11

What was the first hormone isolated from animal sources, first to have structure determined and mechanism of action described?

Answer 11

insulin

Question 12

Which hormone has an amino acid sequence that varies by species with certain segments highly conserved within vertebrates?

Answer 12

insulin

Question 13

Insulin is synthesized as preprohormone with what 4 peptides?

Answer 13

• signal peptide
• A and B chains
• C chain (connecting peptide)

Question 14

What is the structure of insulin?

Answer 14

peptide hormone with 2 chains (A chain and B chain) and 3 disulfide bridges

Question 15

What do the three disulfide bridges of insulin link?

Answer 15

• 2 brdiges link A and B chains together
• third bridge is within the A chain

Question 16

Describe the steps to synthesize insulin.

Answer 16

• synthesized as preprohormone with four peptides
• proinsulin sent to ER, insulin folds and disulfide bridges form
• golgi packages into granules, proteases cut C-peptide
• secretion via exocytosis

Question 17

The most important stimulator of insulin secretion is what?

Answer 17

blood glucose

Question 18

Describe regulation of insulin secretion.

Answer 18

1. transport of glucose into beta cell via GLUT 2 transporter (facilitated diffusion)
2. glucose immediately phosphorylated by glucokinase – ATP is a product
3. ATP closes ATP sensitive K channels – depolarizes membrane
4. depolarization opens voltage gated Ca channels – Ca flows into cell, inrceasing intracellular Ca
5. increase in Ca causes exocytosis of insulin granules into venous blood

Question 19

Does oral or IV glucose cause greatest response due to an “incretin” effect?

Answer 19

oral

Question 20

What substances other than blood glucose stimulate insulin secretion?

Answer 20

• amino acids
• ketoacids
• FFA
• K+, Ca
• GIP, vagal stimulation (Ach), drugs (sulfonylurea drugs)
• glucagon

Question 21

What substances other than blood glucose inhibit insulin secretion?

Answer 21

• fasting
• exercise
• somatostatin
• leptin

Question 22

Describe the mechanism of action of insulin in peripheral cells.

Answer 22

1. insulin binds alpha subunits, causes conformational change, activates tyrosine kinase in beta subunits
2. tyrosine kinase phosphorylates other proteins/enzymes involved in physiologic actions of insulin
3. insulin receptor complex internalized by target cell to be degraded, stored, or recycled

Question 23

Tyrosine kinase (insulin receptor) has four subunits. Where are they?

Answer 23

2 alpha subunits extracellular
2 beta subunits span the mmebrane, have tyrosine kinase on intracellular side

Question 24

What are the actions of insulin?

Answer 24

• when nutrients are available, insulin makes sure those nutrients are stored
• insulin directly stimulates glucose uptake into muscle and fat, but not liver

Question 25

How does insulin store nutrients?

Answer 25

- glucose stored as glycogen in muscle and liver - FFA stored as adipose tissue - Protein stored in muscle

Question 26

What glucose transporters are insulin independent?

Answer 26

- GLUT 1 found in brain, RBC - GLUT 2 found in liver, beta cells of pancreas - GLUT 3 found in brain

Question 27

What glucose transporters are insulin dependent?

Answer 27

- GLUT 4 found in fat, muscle, heart

Question 28

Transport of glucose in intestine and kidneys is NOT regulated by insulin, but is ____ dependent and carried out by what transporter?

Answer 28

- Na dependent - GLUT 5 transporter in intestine

Question 29

What are the effects of insulin on carbohydrate metabolism?

Answer 29

- decreases blood glucose - increases glucose transport into muscle and adipose - promotes glycogen formation in liver and muscle - inhibits gluconeogenesis and glycogenolysis

Question 30

What are the effects of insulin on lipid metabolism?

Answer 30

- inhibits mobilization and oxidation of FA - inhibits ketogenesis in liver - promotes FFA storage as triglycerides - inhibits FFA uptake in muscle - inhibits lipolysis

Question 31

What are the effects of insulin on protein metabolism?

Answer 31

- overall anabolic - decreases blood AA - increases AA and protein uptake by tissues - increases protein synthesis - inhibits protein degradation

Question 32

What are other general effects of insulin not related to a specific metabolism?

Answer 32

- promotes K+ uptake into cells by increasing activity of Na/K ATPase - promotes phosphate, Mg++ uptake into cells - insulin decreases appetite via the satiety center of hyothalamus - excess insulin causes hypoglycemia which stimulates cortisol release to increase appetite

Question 33

What acts as a protective mechanism during acute illness to preserve brain's glucose supply?

Answer 33

insulin resistance

Question 34

Insulin resistance can occur via alterations in what?

Answer 34

insulin receptors (either by decreasing number of receptors or decreasing affinity of receptors for insulin)

Question 35

What is insulin resistance?

Answer 35

- when cells fail to respond normally to insulin - insulin overproduced: blood insulin and glucose remain high

Question 36

What can cause insulin resistance other than alterations to insulin receptors?

Answer 36

- hormones (cortisol, GH, thyroid hormones, epilepsy, estrogen/progesterone) - obesity - liver or kidney failure - sepsis - insulin antibodies

Question 37

What pathophysiology is associated with insulin?

Answer 37

- diabetes mellitus (type 1 and 2) - insulinoma

Question 38

Type 1 diabetes mellitus is due to what?

Answer 38

insulin deficiency

Question 39

Type 2 diabetes mellitus is due to what?

Answer 39

insulin resistance

Question 40

Insulinoma results in what?

Answer 40

excessive insulin production by beta cell tumor

Question 41

What can result from lack of insulin or lack of insulin action?

Answer 41

- hyperglycemia - hyperlipidemia - peripheral tissue protein catabolism

Question 42

True or false: glucagon sequence is identical in all species.

Answer 42

true

Question 43

What stimulates glucagon release?

Answer 43

- hypoglycemia - protein/AA - fasting - stress (especially infection) - intense exercise - cholecystokinin

Question 44

What inhibits glucagon secretion?

Answer 44

- glucose - insulin - somatostatin

Question 45

Glucagon works through stimulation of what to mediate effects?

Answer 45

G-protein/cAMP

Question 46

What are the effects of glucagon?

Answer 46

- increases glycogenolysis, gluconeogenesis, lipolysis, ketoacid formation - little to no effect on glucose utilization by peripheral tissues

Question 47

The action of glucagon are opposite the actions of what hormone?

Answer 47

insulin

Question 48

What pathophysiology is associated with glucagon?

Answer 48

- glucagonoma - hyperglucagonemia/diabetes mellitus associated with infection

Question 49

In hyperglucagonemia, what happens to the ratio of glucagon:insulin?

Answer 49

it increases

Question 50

What is the glucagonoma?

Answer 50

tumor of alpha cells in pancreas

Question 51

What results from a glucagonoma?

Answer 51

results in diabetes mellitus and necrolytic migratory erythema

Question 52

Somatostatin is stimulated by all nutrients, but inhibited by what?

Answer 52

insulin

Question 53

What inhibits somatostatin?

Answer 53

- insulin and glucagon - GI hormones - GI motility, enzymes, gastric acid secretion

Question 54

Somatostatin is secreted by what?

Answer 54

- delta cells of pancreas - hypothalamus - GI cells

Question 55

How does adipose tissue act as an endocrine organ?

Answer 55

secretes hormones influencing feeding behavior, insulin sensitivity, glucose transport

Question 56

What is the action of leptin secreted by adipose tissue?

Answer 56

- inhibits appetite by inhibiting neuropeptide Y - increases BMR

Question 57

What is the action of neuropeptide Y?

Answer 57

increase appetite

Question 58

What is the action of adiponectin secreted by adipose tissue?

Answer 58

- improves insulin sensitivity

Question 59

High adiponectin results in low risk of?

Answer 59

type II diabetes

Question 60

Low adiponectin results in?

Answer 60

obesity and diabetes (cats)

Question 61

What substances are secreted by adipose tissue?

Answer 61

- leptin - tumor necrosis factor - alpha - adiponectin