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FHB Block 4 > L11- Pancreas > Flashcards

L11- Pancreas Flashcards

1
Q

What is a “fatty liver”?

A

Large accumulation of TAGs in the liver- can cause cell death

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2
Q

What enzyme is required for breakdown/utilization of ketone bodies?

A

Thiophorase

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3
Q

What are the islets of Langerhans?

A

They are the endocrine tissue of the pancreas

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4
Q

Which are the majority of cells in the islets? What do they produce?

A

Beta cells- synthesize and secrete insulin

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5
Q

What do alpha cells produce?

A

Alpha cells produce glucagon

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6
Q

What do delta cells produce?

A

Delta cells synthesize and produce somatostatin (SS14)

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7
Q

What are PP cells? What do they secrete?

A

PP cells are endocrine cells in the Islets of Langerhan. They produce pancreatic polypeptide, which inhibits acinar cells via paracrine action.

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8
Q

Which cells in the islet of langerhan are responsible for the production of ghrelin?

A

Epsilon cells

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9
Q

Describe the blood flow in the pancreas- how does this impact the cells of the islet?

A

Blood flows into the islet and then back out again.

Specifically, blood flows into the core of the islet where all of the insulin is produced and then flows back out through the alpha cells.

Functionally, this means that the alpha cells are bathed in newly synthesized insulin from the beta cells.

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10
Q

Which cells make up the “core” of the islet. What surrounds them?

A

Beta cells make up the core of the islet, and they are surrounded by alpha cells

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11
Q

What is the half-life of insulin?

A

The half-life of insulin is very short- around 3-8 minutes

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12
Q

What is the “C” peptide?

A

The c peptide is the co-peptide synthesized with insulin

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13
Q

What can C peptide be used for clinically?

A

C-peptide has a much longer half-life of 35 minutes. It is a good clinical indicator of pancreatic function

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14
Q

What is the importance of the cleavage of the C peptide from newly synthesized insulin?

A

The C peptide must be cleaved off to expose the binding of the end of the insulin chain to the insulin receptor

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15
Q

How does glucose enter the beta cell from the blood?

A

Glucose is transported via GLUT2

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16
Q

What is the GLUT2 affinity for glucose?

A

Low- glucose transport only occurs when plasma glucose levels are high

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17
Q

What is the first thing that happens to glucose after being transported into a beta cell through GLUT2?

A

It is phosphorylated by glucokinase. This “traps” the glucose in the cell

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18
Q

What is responsible for closing the K+ channel in the beta cells?

A

High ATP.

The K+ channels are ATP sensitive and close following an increase of ATP (from glycolysis –> indicative of high plasma glucose)

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19
Q

What is the subunit important for ATP sensing in the ATP-sensitive K+ channel of the beta cells?

A

SUR subunit

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20
Q

WHat is the drug target of sulfonylurea drugs?

A

The SUR subunit of the beta cells. This effectively allows the cell to bypass the necessity for glucose to be taken up and metabolized by the beta cells and leads to insulin release (independent of blood glucose)

Closing the K+ channels leads to depolarization of the cell and opening of Ca2+ channels that allows insulin to be released.

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21
Q

What is the consequence of closing the K+ channels in the beta cells?

A

K+ channels close –> depolarization of the cell –> opening of voltage-gated Ca2+ channels –> insulin release

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22
Q

Other than glucose, what other sources of energy can lead to a rise in ATP in the beta cells, and consequently the release of insulin?

A

Free fatty acids (for sure) and amino acids (but not so much- little insulin

23
Q

What is the role of incretins? Name a few.

A

Incretins (such as glucagon-like peptide 1 and 2) potentiate insulin release.

They act through G-coupled protein receptors –> cAMP —> more Ca2+ released from intracellular stores –> a little bit more insulin is released

They can’t work on their own, they still require glucose to work

24
Q

How to catecholamines affect insulin release?

A

Catecholamines inhibit the release of insulin from beta cells

They bind to alpha-adrenergic receptors in the pancreas

Exercise limits insulin release

25
Q

Differentiate the first phase of insulin secretion from the second phase of insulin secretion.

A

First phase: vesicles are stored with insulin for immediate release –> sharp rise in insulin levels

Second phase: Once the initial vesicles dump their insulin, insulin from either storage or newly synthesized is slowly released

26
Q

What type of receptor is the insulin receptor?

A

Tyrosine Kinase

27
Q

Differentiate the alpha from the beta subunit of the insulin receptor

A

Alpha: extracellular, binds insulin
Beta: intracellular, beta subunit is autophosphorylated following insulin binding

28
Q

What types of tissue require GLUT4 transporters for the uptake of glucose?

A

Skeletal muscle and adipose tissue

29
Q

What does it mean that GLUT4 is insulin-dependent?

A

GLUT4 requires insulin signaling for insertion into the cell membrane.

30
Q

How does insulin signaling lead to insertion of GLUT4 into the cell membrane?

A

Insulin binds alpha subunit –> autophosphorylation of the intracellular beta subunit –> recruitment of insulin receptor substrates –> intracellular signaling cascades –> GLUT4 insertion into the membrane

31
Q

Which is the only glucose transporter that is dependent on insulin?

A

GLUT4, present in adipose tissue and skeletal muscle

32
Q

What is the primary action of insulin?

A

energy storage

33
Q

What are the primary tissue targets of insulin?

A

Liver, Muscle and Fat

34
Q

Incretins are processed by the same prohormone as what hormone?

A

Glucagon

35
Q

WHat type of nutrient best stimulates the release of glucagon?

A

Proteins

36
Q

How does exercise stimulate the release of glucagon?

A

THrough catecholamine production –binding of alpha-adrenergic receptors

37
Q

What is the primary action of glucagon?

A

Energy mobilization

38
Q

What are the main targets of glucagon?

A

Liver and adipose tissue

39
Q

How does insulin affect alpha cells of the islet of langerhan?

A

Insulin directly inhibits alpha cells- and because the blood flows from the beta cells (full of insulin) to the alpha cells, insulin release will directly inhibit glucagon release from alpha cells

40
Q

How do catecholamines affect alpha and beta cells?

A

Catecholamines inhibits beta cells and stimulates alpha cells

41
Q

Which form of somatostatin is produced in the pancreas? Which cells secrete it?

A

Somatostatin 14 (SS14), produced and secreted by delta cells (D cells)

42
Q

What nutrients stimulate somatostatin 14?

A

High fat and high carb meals- this causes digestion to slow down

43
Q

How are large doses of somatostatin used clinically?

A

Large doses of exogenous somatostatin suppress insulin release –> used clinically to inhibit insulin release from insulin secreting tumors

44
Q

What cells secrete amylin? What is it secreted with?

A

Amylin is released with insulin from vesicles in beta cells

45
Q

What is the role of amylin?

A

Amylin works synergistically with insulin to control blood glucose levels

46
Q

How is amyloid thought to be connected to beta cell destruction?

A

Excessive release of amyloid in obese people is thought to form amyloid plaques that lead to the destruction of beta cells

47
Q

Most circulating ghrelin is produced where?

A

Stomach

48
Q

What are the two major actions of ghrelin?

A

1) Stimulates food intake (at the level of the hypothalamus

2) Stimulates release of GH

49
Q

What is the correlation between ghrelin and obesity

A

There is an inverse relationship between circulating ghrelin levels and obesity (your body senses that you need to stop eating food for god’s sake)

50
Q

What are the paracrine actions of ghrelin?

A

decreases insulin release

51
Q

What two hormones have secondary counter regulatory effects to insulin?

A

Growth hormone and cortisol - they act as a defense against prolonged hypoglycemia (starving)

52
Q

How do catecholamines and epinephrine act as counter regulators to insulin?

A

They act to increase plasma glucose levels to make glucose available to the brain and heart in times of stress

53
Q

Protein primarily stimulates the release of what hormone?

A

glucagon

54
Q

When insulin is present, amino acids from protein stimulate what hormone? What is the effect?

A

Growth hormone- growth hormone stimulates the release of IGF-1 from the liver. IGF-1 stimulates glucose uptake in muscle, proliferation of visceral organ tissues, and inhibits proteolysis

Growth hormone also opposes insulin lipogenesis (because growth hormone promotes lean-muscle- lead body mass)

FHB Block 4 (15 decks)

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