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SMP - MNE Exam 1 > Lecture 12: Endocrinology of the Pancreas > Flashcards

Lecture 12: Endocrinology of the Pancreas Flashcards

1
Q

What is the difference between endocrine and exocrine?

A

Endocrine: releases hormones in the blood
Exocrine: release enzymes through ducts to outside the body or onto another surface within the body

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2
Q

What are the endocrine and exocrine cells of the pancreas?

A
  • Endocrine: Islets of Langerhans secrete insulin and glucagon in blood
  • Exocrine: Acinar cells secrete pancreatic enzymes into the pancreatic duct which runs to the GIT lumen
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3
Q

What are the 5 cell types of the islets of Langerhans and their % in the islets?

A
  1. Alpha: 15%
  2. Beta: 60%
  3. Delta: 10%
  4. Epsilon
  5. F: 15%
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4
Q

What 2 hormones do the alpha cells of the islets of Langerhans produce?

A
  1. Glucagon

2. Ghrelin

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5
Q

What 5 hormones do the beta cells of the islets of Langerhans produce?

A
  1. Insulin
  2. Proinsulin
  3. C peptide
  4. Amylin
  5. Possibly ghrelin
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6
Q

What hormone do the delta cells of the islets of Langerhans produce?

A

Somatostatin

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7
Q

What hormone do the epsilon cells of the islets of Langerhans produce?

A

Ghrelin

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8
Q

What hormone do the F cells of the islets of Langerhans produce?

A

Pancreatic polypeptide

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9
Q

What does ghrelin stimulate?

A

Appetite

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10
Q

What does orexigenic mean?

A

Appetite stimulant

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11
Q

How are the 5 different cell types of the islets of langerhans arranged in space in the pancreas?

A 
Alpha: periphery
Beta: center 
Delta: scattered 
Epsilon: periphery
F: ventral
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12
Q

How does arterial blood flow go through the islets of langerhans of the pancreas?

A

Enters in the center and spread outward to the periphery

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13
Q

What kind of hormone actions happen within the islets of langerhans of the pancreas?

A

Paracrine and autocrine

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14
Q

What does secretatogue mean?

A

Substance that promotes secretion

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15
Q

How does glucagon affect insulin secretion by beta cells?

A

Glucagon is a powerful secretatogue of insulin, but because the alpha cells are on the periphery of the islets and the beta cells are in the center, the blood flow diminishes this effect

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16
Q

How are pancreatic hormones released in the blood stream?

A

Through fenestrations in endothelial wall of the pancreas

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17
Q

What 2 arteries provides blood to the pancreas?

A
  1. Splenic artery

2. Superior mesenteric artery

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18
Q

Where are the hormones produced by the islets of langerhans of the pancreas transported to once they are secreted into the blood stream? How?

A

To the liver via the portal vein

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19
Q

What 3 veins is the portal vein formed by?

A
  1. Splenic vein
  2. Superior mesenteric vein
  3. Inferior mesenteric
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20
Q

How does ghrelin secretion by the epsilon cells affect the other cells of the islets of langerhans?

A
  1. Inhibits alpha cells

2. Inhibits beta cells

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21
Q

How does somatostatin secretion by the delta cells affect the other cells of the islets of langerhans?

A
  1. Inhibits alpha cells

2. Inhibits beta cells

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22
Q

How does glucagon secretion by the alpha cells affect the other cells of the islets of langerhans?

A
  1. Stimulates delta cells

2. Stimulates beta cells

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23
Q

How does insulin secretion by the beta cells affect the other cells of the islets of langerhans?

A

Inhibits alpha cells

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24
Q

What is the average fasting blood glucose level?

A

60-80 mg/dl

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25
Q

What is the average blood glucose level after a meal?

A

100-140 mg/dl

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26
Q

What is the ratio of insulin to glucagon during fasting?

A

1:10

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27
Q

What is the ratio of insulin to glucagon after a meal?

A

1:2

28
Q

What part of the C-peptide signals enzymes to cleave it off proinsulin? What are these enzymes? Where does this happen?

A

2 pairs of basic residues
Intracellular convertases
In the Golgi

29
Q

What happens to 100% of the C-peptide?

A

Urinated

30
Q

What is a good test to measure the amount of insulin produced in a given period?

A

Measure C-peptide concentration in the urine

31
Q

What % of the insulin produced by the pancreas is taken up by the liver in one pass?

A

60%

32
Q

What happens to the insulin levels if you transfuse glucose via IV? 2 parts and overall? What is this due to?

A

Overall: insulin levels remain low

  1. Acute/first-phase insulin response (2-5 min): pre-formed insulin is rapidly released
  2. Second phase (hump): synthesized insulin

REASON: because of the incretins regulation of insulin secretion

33
Q

Describe the insulin secretion pathway.

A
  1. Glucose enters pancreatic beta cells via GLUT2 transporters
  2. Glucose is phosphorylated by hexokinase 4 to G6P (trapping it inside the cell)
  3. ATP produced through glycolysis, TCA, and ETC
  4. ATP binds to the K+ channels and inhibit them = cell depolarization
  5. VG calcium channels open and calcium rushed in
  6. Fusion of insulin containing granules with plasma membrane = insulin release
34
Q

Describe GLUT 2 and hexokinase’s affinities for glucose. What does this mean for the kinetics of the reactions?

A

Very high Kms: linear kinetics, meaning the concentration of glucose in the beta cells is proportional to the concentration of glucose in the blood because an enzyme with a high Km achieves maximum rate at a higher concentration. Thus, it will continue to respond to higher concentrations by increasing its rate. It thus “responds” to a greater range of concentrations.

35
Q

What is genepin? What is its effect on insulin secretion?

A

Inhibitor of uncoupling
Effect on insulin secretion: blocks uncoupling of H+ gradient in mito => increased ATP synthesis = increased insulin secretion

36
Q

What is uncoupling?

A

Process where a certain molecule is able to transport ions from one side of the membrane to the other down their concentration gradient, thus dissipating the gradient

37
Q

What are the 11 ways in which insulin secretion is regulated?

A
  1. Glucose blood levels
  2. Fructose blood levels
  3. FA blood levels
  4. AA blood levels (Arg/Leu)
  5. SNS
  6. PSNS
  7. Incretins secretion
  8. Glucagon
  9. Ghrelin
  10. Somatostatin
  11. Leptin
38
Q

What are the 2 ways in which the islets of langerhans are richly innervated to STIMULATE insulin secretion?

A
  1. SNS: beta adrenergic receptors to epinephrine

2. PSN: nicotinic receptors to acetylcholine

39
Q

Describe how the SNS regulates insulin secretion. 4 steps

A
  1. Beta adrenergic agonists activate adenylyl cyclase via GPCR mechanism
  2. cAMP synthesis
  3. PKA activation
  4. Insulin secretion stimulation
40
Q

How do alpha adrenergic receptor agonists affect insulin secretion? What is this important for? Example?

A

Inhibit it by inhibiting the adenylyl cyclase
This is important during exercising: alpha receptors are stimulated to avoid hypoglycemia and force the muscles to use their glycogen stores

Eg: norepi

41
Q

What would happen if someone injected insulin while exercising?

A
  1. Increase muscle uptake of glucose
  2. Inhibit lipolysis and FA release
  3. Inhibit gluconeogenesis
    = hypoglycemia
42
Q

Describe how the PNS regulates insulin secretion. 3 steps.

A
  1. ACh binds to the receptors to stimulate phospholipase C
  2. PLC degrades membrane phospholipids into DAG and IP3
    3a. DAG stimulates PKC to stimulate insulin secretion
    3b. IP3 travels to ER to release calcium to stimulate insulin secretion
43
Q

Describe how the secretion of incretins regulates insulin secretion.

A
  1. Duodenum receives carb
  2. GIT releases incretins
  3. Insulin secretions is stimulated
44
Q

What are 3 examples of incretins?

A
  1. Cholescystokinin (CCK)
  2. Gastric inhibitory peptide (GIP)
  3. Glucagon-like peptide-1 (GLP-1)
45
Q

How does GLP-1 stimulate insulin secretion? 2 ways

A
  1. It activates a portal sensor in the portal vein that signals (via vagal afferents) the CNS to enhance insulin secretion (via vagal afferents)
  2. It binds its receptors on the beta cells of the pancreas
46
Q

How does GIP stimulate insulin secretion?

A

It binds its receptors on the beta cells of the pancreas

47
Q

Describe what happens during beta-cell exhaustion in T2D.

A

Eating sugary foods all the time causes increase in insulin demand and the beta cells enlarge and burn out (apoptosis) and we also increase our resistance to insulin

48
Q

Describe what happens during amyloid deposition in T2D.

A

Amylin is secreted from beta cells with a 1:100 ratio with insulin to slow gastric emptying to promote satiety and prevent post-prandial spikes in blood glucose (decreasing rate of carb uptake) BUT a certain AA sequence of it causes beta-amyloid plaque formations in the beta cells when secreted too much (badly processes and too many of them), which can kill the beta cells and add pressure to remaining cells

49
Q

What has been found to prevent amyloid plaque formation on beta cells and amylin synthesis? Why?

A

Coffee because it contains polyphenols and caffeine metabolites (caffeic acid and chlorogenic acid)

50
Q

Is response to what is glucagon secreted?

A
  1. Protein ingestion: increase in plasma AAs
  2. SNS: alpha adrenergic agonists (norepi)
  3. Low blood glucose
51
Q

What does glucagon promote?

A
  1. Gluconeogenesis
  2. Mobilization of glycogen stores in the liver
  3. Lipolysis
  4. Ketogenesis
52
Q

Do incretins regulate glucagon?

A

Yes

53
Q

How is ghrelin secretion affected by bariatric surgery?

A

Dramatically suppressed

54
Q

Which cells of the Islets of Langerhans are basically stem cells and can further differentiate into the other types of cells of the islets?

A

Epsilon cells

55
Q

Are all cell types of the islets of langerhans accessible on the surface?

A

Yes

56
Q

From what germ layer do beta cells arise from?

A

Endoderm

57
Q

Why do people who develop Type 2 diabetes keep eating sugary foods?

A

Because insulin levels rise fast in response to high sugar foods, so you get hungry again very fast

58
Q

What is the other possible pathway instead of beta cell failure?

A

More robust beta cells and sustained adaptation

59
Q

What is IAPP?

A

Insulin Amyloid PolyPeptide

60
Q

How many AAs in amylin?

A

37

61
Q

How many AAs in glucagon?

A

31

62
Q

What is the endocrine pancreas derived from?

A

Pancreatic diverticula/buds

63
Q

How does leptin regulate insulin secretion?

A

It inhibits it

64
Q

What are the 4 inhibitors of glucagon secretion?

A
  1. Increase in blood FAs
  2. Increase in blood glucose
  3. Somatostatin
  4. Insulin
65
Q

What cells of the islets does diabetes affect?

A
  1. Beta

2. Alpha

66
Q

What other organ secretes ghrelin?

A

Stomach

67
Q

What are the 2 opposite hormones to ghrelin?

A

Leptin and amylin

SMP - MNE Exam 1 (25 decks)

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