Endocrine Pancreas

Question 1

What are the endocrine cells in the pancreas and what do they secrete?

Answer 1

alpha = glucagon

beta = insulin, C peptide

delta = somatostatin

Question 2

How are the endocrine cells arranged in islets?

Answer 2

betas in the center

alpha and delta in the periphery

(alpha and delta get bathed in insulin)

Question 3

What does sympathetic stimulation do to the pancreas?

Parasympathetic?

Answer 3

alpha adrenergic signal –> decreased insulin

ACh –> increased insulin

Question 4

How do cells of pancreatic islets communicate with each other?

Answer 4

gap jxns = rapid cell-to-cell communication btw a-a, a-b, b-b

blood flows into center of islets first –> goes out = all cells get bathed in insulin

Question 5

How do delta cells affect beta and alpha cells?

Answer 5

somatostatin inhibits insulin and glucacon secretion

Question 6

How do beta cells affect alpha and delta cells?

Answer 6

beta cells inhibit alpha cells

alpha cells promote insulin

delta cells inhibit beta cells

Question 7

How are the alpha and beta strands of insulin held together?

Answer 7

by 2 disulfide bridges

C peptide initially holds them together but is then cleaved to form the active hormone

Question 8

What is the main stimulus for insulin?

Answer 8

carbohydrate or protein-containing meal –> high glucose levels

Question 9

What is the difference between preproinsulin, proinsulin, and insulin?

Answer 9

preproinsulin = signal peptide, A and B chains, and connecting peptide

proinsulin = no signal peptide; C peptide, disulfide bridges form in ER –> packaged in vesicles in golgi

during packaging, proteases cleave proinsulin

Question 10

What is the importance of C peptide?

Answer 10

insulin and C peptide are packed together in secretory vesicles –> secreted in 1:1 ration

C peptide can be used as long-term marker of Beta cell function and insulin secretion

Question 11

How does glucose signal insulin release?

Answer 11

glucose binds glut2 – glucokinase –> G-6-P –> makes ATP –> closes K+ channels –> cell depolarizes –> voltage-gated Ca channels open –> exocytosis of insulin and C peptide

Question 12

What do sulfonurea drugs do?

Answer 12

promote the closing of ATP-dependent K+ channels (glucose signals this) –> so that more insulin will be secreted

used to treat T2DM

Question 13

How is insulin secreated in response to glucose?

Answer 13

biphasic manner

phase 1 = preformed vesicles released

phase 2 = preformed and newly synthesized insulin released

Question 14

In diabetic ppl, what is the first thing to disappear?

Answer 14

the first phase/ acute insulin response

Question 15

How do CCK and ACh contribute to insulin release?

Answer 15

both bind Gq receptor –> PLC –> IP3 and DAG –> both calcium and PkC signal insulin release

Question 16

How does somatostatin contribute to insulin release?

Answer 16

binds Gi –> inhibits cAMP and PkA –> inhibits insulin release

Question 17

How do glucagon and GLP-1 contribute to insulin release?

Answer 17

Binds Gs receptor –> cAMP –> PkA –> insulin release triggered

Question 18

What happens (in general) when insulin binds its receptor?

Answer 18

receptor phosphorylates itself and other proteins –> insulin-receptor complex is internalized by target cell –> glucose transport, protein, fat, and glycogen synthesis; growth and gene expression

Question 19

How does insulin affect its own receptor?

Answer 19

down regulates its own receptor

Question 20

What is the relationship btw insulin and the liver?

Answer 20

insulin released from pancreas –> to liver, can take up insulin and receptor and cleave –> actual levels in systemic circulation are a lot less than what is initially released from the pancreas

Question 21

What receptors do insulin upregulate in cell membranes?

Answer 21

GLUT4 in muscle and adipose tissue

GLUT2 in liver

other GLUTs

Question 22

How does insulin induce metabolic effects?

Answer 22

binds receptor –> Piates –> IRS1-4 –> PI3K –> PIP3 –> pkB/AKT –> metabolic effects

*include GLUT translocation and activation of protein postphatases

Question 23

How does insulin induce growth effects?

Answer 23

insulin + receptor –> Piates –> IRS1-4 –> SHC –> GRB/SOS –> RAS/GTP –> MAPK –> growth effects

Question 24

How does insulin affect glycogen?

Answer 24

increases glucogen synthase

upregulates hexokinase (glucokinase in liver and beta cells)

activates glycogen synthase

Question 25

How does insulin affect protein and fat metabolism?

Answer 25

increases protein synthesis and decreases protein breakdown favors FAs --\> triglycerides (lipogenesis) inhibits triglycerides --\> FAs by inhibiting hormone-sensitive lipase

Question 26

How does excercise affect insulin and glucose metabolism?

Answer 26

muscle contractions stimulate AMPK --\> GLUT4 into membranes --\> helps uptake of glucose and decreases insulin resistance

Question 27

How does insulin affect blood levels of nutrients?

Answer 27

decreases: glucose, FAs, ketoacids, amino acids (basically puts it all in cells)

Question 28

How does insulin affect K+ levels?

Answer 28

increases K+ uptake into cells and lowers plasma K glucose and insulin can be given to treat hyperkalemia

Question 29

When do symptoms of T1DM become evident?

Answer 29

not until 80% of beta cells are destroyed

Question 30

What occurs to induce diabetic ketoacidosis?

Answer 30

increased conversion of FA to ketoacids and decreased ketoacid utilization by tissues

Question 31

What things do you see increased in the blood in T1DM?

Answer 31

glucose fatty acids and ketoacids amino acids K+ (even though total body K is usually low)

Question 32

What occurs to induce hyperkalemia in type 1 diabetics?

Answer 32

insulin doesn't have effect on Na/K ATPase --\> K shifts out of cells --\> plasma levels become high, but total is usually low bc of polyuria and dehydration

Question 33

What occurs in osmotic diuresis?

Answer 33

increased blood glucose --\> increased filtered load of glucose, exceeding reabsorptive capacity of PCT water and electrolyte reabsorption is also prevented Polyuria: increased excretion of Na and K even though urine concentration of electrolytes is low

Question 34

What are the main drawbacks of insulin replacement therapy?

Answer 34

lag btw glucose measurement and insulin dosing, delayed absorption of insulin following injection --\> periods of hyperglycemia

Question 35

What occurs in the progression of T2DM?

Answer 35

initially high insulin levels and insulin resistance --\> progressive exhaustion of beta cells --\> insulin deficiency later

Question 36

What are teh 3 causes for obesity-induced insulin resistance?

Answer 36

decreased GLUT-4 uptake of glucose in response to insulin decreased ability of insulin to repress hepatic glucose production inability of insulin to **repress** hormone-sensitive lipase (**HSL**) or **increase** lipoprotein lipase (**LPL**)

Question 37

What is the current understanding of insulin resistance?

Answer 37

not well understood might be due to post-receptor signaling --\> ultimately results in less gluts in membranes \*may be bc insulin receptor or downstream proteins aren't Piated

Question 38

What do biguanide drugs do?

Answer 38

upregulate insulin receptors on target tissues (metformin)

Question 39

What is the difference in effects of IV glucose vs oral glucose?

Answer 39

insulin is much more affected by oral glucose than IV

Question 40

What are incretin hormones and what do they do?

Answer 40

intestine-derived, short T1/2 GLP-1, GIP GI glucose and fat --\> stimulate insulin secretion, inhibit glucagon, slow gastric emptying

Question 41

What is the reduced incretin effect?

Answer 41

in type 2 diabetics, oral glucose fails to result a mich higher peak of insulin that is seen in normal ppl bc incretins aren't working to increase insulin

Question 42

Which form of diabetes has more of a genetic component?

Answer 42

type 2 = 50% family link rather than 10-20 for type 1

Question 43

What hormones have a hyperglycemic action?

Answer 43

glucagon epinephrine cortisol growth hormone

Question 44

What other hormones are part of the same family as glucagon? How do they differ?

Answer 44

GLPs are in same family proglucagon --\> processing in alpha cells --\> glucagon proglucagon --\> processing in intestinal L cells --\> GLP-1 and GLP-2

Question 45

How is glucagon stored?

Answer 45

in dense granules until alpha cells are stimulated

Question 46

What is the main stimulus for glucagon secretion? How does it work?

Answer 46

low glucose no glut signaling --\> increased ATP --\> K channel inhibited, Na and Ca channels open --\> Ca stimulates glucagon release

Question 47

Besides low glucose, what other things stimulate glucagon release?

Answer 47

amino acids fasting CCK beta adrenergic agonists ACh

Question 48

What things inhibit glucagon synthesis and secretion?

Answer 48

insulin somatostatin increased FA and ketoacid concentration

Question 49

What are the major actions of glucagon?

Answer 49

increases glycogen breakdown Glucagon --\> cAMP --\> PKA --\> inhibits production of fructose 2,6-biPi --\> substrates directed toward glucose formation

Question 50

How does glucagon affect lipid metabolism?

Answer 50

increases lipolysis and inhibits FA synthesis shunts substrates toward gluconeogenesis increased blood glucose, FAs, and ketoacids

Question 51

What do F cells do?

Answer 51

release pancreatic peptide acts like a satiety signal like neuropeptide Y