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FHB Exam 4 > Endocrine 10: Pancreas > Flashcards

Endocrine 10: Pancreas Flashcards

1
Q

What are the major cell types of the pancreas and what do they produce?

A

Collectively called the islet of langerhans

  • Beta cells produce insulin
  • Alpha cells produce glucagon
  • Delta cells produce somatostatin 14
  • PP cells produce pancreatic polypeptide
  • Epsilon cells produce ghrelin
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2
Q

What are the overall functions of the major pancreatic hormones?

A 
insulin = energy anabolism (storage)
glucagon = energy catabolism (breakdown)
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3
Q

Describe the cellular arrangement of the islet of Langerhans.

A
  • core = beta cells
  • alpha and delta cells surround it
  • highly vascularized
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4
Q

Describe the pancreatic blood supply.

A

arterioles project into the pancreatic core of beta cells

  • they take insulin rich blood and project to the surrounding cells
  • hence, insulin can have an effect on alpha (glucagon-producing) cells, but NOT the other way around
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5
Q

Describe the structure of insulin.

A

signal peptide = B chain = C chain = A chain

  • signal peptide cleaved
  • chains wrap around themselves
  • disulfide bonds formed between A and B chain
  • in the vesicle, C chain is cleaved
  • vesicle releases both insulin and C-peptide
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6
Q

What is the significance of C-peptide?

A
  • long half life

- good indicator of pancreatic function

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7
Q

Describe the mechanism of action of insulin release from pancreatic beta cells.

A
  1. High plasma glucose activates GLUT2 on the B cell membrane => glucose enters the cell
  2. glucose => glycolysis => ATP production
  3. High ATP levels close K channel
  4. K buildup inside cell => depolarization
  5. depolarization activates voltage-gated Ca2+ channels
  6. influx of Ca => insulin vesicle release
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8
Q

What is the function of glucokinase in beta cells?

A

act as glucose sensor

- phosphorylation of glucose to G6P

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9
Q

What is a unique feature of the ATP-sensitive K channels in beta cells?

A
  • contain sulfonylurea (SUR) subunit
  • drug target for sulfonylurea drugs
    ==> keeps K channel closed to force cell to release insulin
    (but ONLY if it can still make it
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10
Q

What are other modulatory pathways of insulin release?

A
  • FFAs and AAs will also form ATP => insulin release
  • incretins (GLPs) will potentiate intracellular calcium release => insulin release (but ONLY in the presence of glucose)
  • catecholamines inhibit alpha-adrenergic receptors and inhibit calcium release => inhibit insulin release
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11
Q

Describe the basis of the biphasic insulin response to a meal.

A
  • first stage results from insulin that is already formed, docked, and ready to go
  • second stage results from newly stimulated and formed insulin (takes longer)
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12
Q

What is the insulin receptor?

A

receptor tyrosine kinase

  • alpha subunit is extracellular and binds insulin
  • beta subunit is intracellular and autophosphorylates in response to insulin
  • beta subunit autophosphorylation recruits intracellular proteins for further downstream signaling cascades
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13
Q

Describe the downstream signaling of insulin in muscle cells.

A
  1. RTKs phosphorylation of beta subunit
  2. recruits IRSs (insulin receptor substrates)
  3. activates RAS/MAPK to promote growth
  4. activates PKB/TC10 to translocate GLUT4 (insulin dependent) glucose transporters to the cell surface

Hence, in muscles, there is no glucose uptake without insulin

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14
Q

GLUT1

  • expression
  • function
A

Expression

  • brain vasculature (major)
  • heart, SM (minor)

Function

  • insulin independent
  • basal uptake
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15
Q

GLUT2

  • expression
  • function
A

Expression

  • pancreatic beta cells
  • liver, kidney, gut

Function

  • insulin independent
  • low affinity (needs high glucose; postprandial)
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16
Q

GLUT3

  • expression
  • function
A

Expression
- neurons

Functions
- insulin independent

17
Q

GLUT4

  • expression
  • function
A

Expression

  • muscles
  • fat

Function
- insulin DEPENDENT

18
Q

GLUT5

  • expression
  • function
A

Expression

  • small intestine
  • spermatazoa

Function
- fructose absorption

19
Q

Describe major physiological effects of insulin target tissues.

A

Liver

  • glycogen synthesis
  • lipogenesis
  • inhibits gluconeogenesis

Muscle

  • glyogen synthesis
  • lipogenesis
  • promotes protein synthesis
  • promotes glucose uptake by transcription of GLUT4

Fat

  • lipogenesis
  • glycolysis
  • inhibits lipolysis

directly inhibits alpha pancreatic cells - no glucagon

20
Q

Describe glucagon structure.

A
  • preprohormone = SP + GRPP + GLUC + GLP1 + GLP2
  • pancreatic hormone = GRPP + GLUC (active)
  • intestinal hormone = glicentin (inactive GRPP-GLUC) + GLP1 + GLP2 (active incretins)
21
Q

When is glucagon released?

A
  • low BG
  • counterregulation of insulin
  • stimulated by protein
  • stimulated by catecholamines
22
Q

Describe physiological effects of glucagon on target cells.

A

Liver
- gluconeogenesis

NO EFFECTS ON MUSCLE

Fat

  • lipolysis
  • glycogenolysis
  • ketogenesis
23
Q

What is required for ketogenesis?

A

NO INSULIN

24
Q

Describe the effects and regulation of pancreatic SS14.

A
  • made by delta cells
  • stimulated by high fat and CHO
  • inhibited by insulin
  • clinically, used to inhibit insulin release from insulin producing tumors
25
Q

Describe the effects and regulation of pancreatic amylin.

A
  • made by beta cells
  • promotes insulin activity
  • high in obesity and HTN
  • formation of amyloid plaques could exacerbate T2DM
26
Q

Describe the effects and regulation of pancreatic ghrelin.

A
  • typically, peptide is made in stomach to promote hunger and anticipation of food (activates GHRH)
  • low in obesity (b/c don’t need to eat)
  • made by epsilon cells of pancreas
  • inhibits insulin by keeping K channels open (no depolarization = no insulin release)
27
Q

What are the insulin counter-regulatory hormones?

A
  • primary = glucagon
  • delayed = GH and cortisol (defends against starvation)
  • catecholamines - inhibits insulin release, stimulates glucagon; increased in exercise/stress, gluconeogenesis, decreased glucose uptake
28
Q

Describe the relationship between insulin, GH, and IGF1.

A
  • protein stimulates GH => IGF (in presence of insulin)
  • IGF stimulates glucose uptake in muscles, proliferation, inhibits proteolysis
  • GH opposes insulin lipogenesis

FHB Exam 4 (16 decks)

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