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BMS150 Post-MT2 > Energy Homeostasis - The Endocrine Pancreas > Flashcards

Energy Homeostasis - The Endocrine Pancreas Flashcards

1
Q

What are pancreatic islet cells made up of? (4)

A
  • Alpha cells
  • Beta cells
  • Delta cells
  • PP cells
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2
Q

Islet cells are a rich ____ supply

A

Capillary

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3
Q

Blood flow in the islet cell?

A

From the center of the islet cell to the periphery

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4
Q

Cell type making up 70% of pancreatic islet?

A

Beta cell

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5
Q

Cell type making up 20% of pancreatic islet?

A

Alpha cell

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6
Q

Cell type making up 5-10% of pancreatic islet?

A

Delta cell

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7
Q

Hormone secreted by alpha cell?

A

Glucagon

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8
Q

Hormone secreted by beta cell?

A

Insulin

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9
Q

Hormone secreted by delta cell?

A

Somatostatin

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10
Q

Hormone secreted by PP cell?

A

Pancreatic polypeptide

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11
Q

General functions of alpha cell? (2)

A
  • Increase blood glucose
  • Make stored energy available
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12
Q

General functions of beta cell? (2)

A
  • Decrease blood glucose
  • Cause entry of glucose into cells
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13
Q

General function of delta cells?

A

Inhibits release of other islet hormones

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14
Q

What kind of feedback loop is glucose homeostasis?

A

Negative feedback loop

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15
Q

What happens if glucose drops under 3 mmol/L?

A
  • Insulin secretion rapidly drops
  • Epinephrine and glucagon secretion increase
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16
Q

Why is hypoglycemia immediately much more harmful than hyperglycemia?

A

Multiple hormones increase blood glucose, but only one (insulin) drops it

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17
Q

Where in the beta cell does insulin synthesis take place?

A

Islets of Langerhans

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18
Q

Insulin transcription

A

Transcription of insulin gene (INS) into mRNA in beta-cell nucleus

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19
Q

Insulin mRNA processing (3)

A
  • Capping
  • Splicing
  • Polyadenylation
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20
Q

Insulin translation (2)

A
  • mRNA exits nucleus => cytoplasm and binds to ribosomes
  • Ribosomes assemble polypeptide chain
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21
Q

What is the polypeptide chain that is synthesized by the ribosome in the beta cell called?

A

Pro-insulin

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22
Q

What domains does pro-insulin contain? (3)

A
  • A chain
  • B chain
  • Connecting C-peptide
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23
Q

What happens as the proinsulin polypeptide elongates?

A

Folds into a 3D structure

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24
Q

Where does proinsulin undergo post-translational modification?

A

Within the ER and Golgi

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25
Q

What happens during pro-insulin processing?

A

Cleavage of C-peptide = mature insulin + C-peptide

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26
Q

Once processed, mature insulin molecules are packaged into what?

A

Secretory vesicles

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27
Q

What are the enzymes and proteins in secretory vesicles necessary for?

A

Regulation of insulin secretion

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28
Q

What does a rise in glucose levels trigger?

A

Signalling pathway triggering the fusion of insulin containing vesicles with the cell membrane => release insulin into bloodstream

29
Q

How does insulin circulate in the bloodstream?

30
Q

Enzyme that degrades insulin? Where is it found?

A
  • Insulinase
  • In the liver, kidneys, and other tissues
31
Q

What can you measure to determine how much endogenous insulin is secreted by diabetics?

A

C-peptide since released alongside insulin

32
Q

Blood glucose concentrations change the ratio of ADP:ATP, what does this change?

A

Membrane potential by changing potassium conductance

33
Q

What happens when insulin binds to its receptor? (2)

A
  • Dimerization
  • Activates Tyr-K activity (autophosphorylation)
34
Q

Key GPCR pathways in insulin receptor activation? (2)

A
  • PI3K pathway => Akt and mTOR activation
  • Ras => Raf => MAPK
35
Q

What happens to cells that are chronically exposed to high levels of insulin?

A

Receptor desensitization

36
Q

What is receptor desensitization? (2)

A
  • Reduce number of insulin receptors expressed
  • Down-regulates some signaling pathways distal to receptor activation
37
Q

What nutrients stimulate insulin secretion? (3)

A
  • Glucose (major)
  • Amino acids (Arg, Lys)
  • FFAs
38
Q

What hormonal signals stimulate insulin secretion?

A
  • CCK, GIP = incretins
  • Parasympathetic innervation
  • GH
39
Q

What hormones inhibit insulin secretion? (3)

A
  • Somatostatin
  • Epinephrine
  • Leptin
40
Q

Where are incretins released from?

A

The intestines

41
Q

Glucose travels in what direction along its concentration gradient?

42
Q

Why can’t glucose molecules freely diffuse through cell membranes?

A

Hydrophilic nature

43
Q

Primary facilitators of glucose transport?

A

GLUT family of proteins

44
Q

Where is GLUT1 found? What does it ensure?

A
  • Brain
  • RBCs
  • Placenta
  • Ensures basal glucose uptake
45
Q

Where is GLUT2 found? What does it ensure?

A
  • Liver
  • Pancreas
  • Kidneys
  • Participates in glucose sensing and hepatic glucose uptake
46
Q

Where is GLUT3 found? What does it ensure?

A
  • Neurons
  • Glucose reuptake in the brain
47
Q

Where is GLUT4 found? What does it ensure?

A
  • Skeletal muscle
  • Adipose tissue
  • Insulin-sensitive and has major role in postprandial glucose uptake
48
Q

Glucose transport mechanism?

A

Facilitated diffusion = conformational change

49
Q

Insulin-independent glucose transporters? Where are they?

A
  • SGLT-1 and SGLT-2: intestine and kidneys
  • GLUT-1 and GLUT-3: wide distribution
  • GLUT-2: liver and pancreas
50
Q

Insulin-dependent glucose transporters? Where are they?

A
  • GLUT-4
  • Skeletal and cardiac muscles and adipose tissue
51
Q

What accounts for roughly 80% of insulin-mediated glucose uptake?

A

Skeletal muscle

52
Q

Insulin - Liver effects? (5)

A
  1. Increased glucose uptake from bloodstream
  2. Increased glucose use
  3. Increased FA and VLDL synthesis
  4. Decreased ketogenesis
  5. Increased protein synthesis
53
Q

Insulin - Muscle effects? (4)

A
  1. Increased glucose uptake by increasing GLUT-4 availability
  2. Increased glucose use
  3. Increased aa uptake and protein synthesis
  4. Increased Na-K ATPase activity
54
Q

Insulin - adipose effects? (5)

A
  1. Increased glucose uptake by increasing GLUT-4 availability
  2. Increased glucose use
  3. Increased TG production (esterification of fats)
  4. Decreased lipolysis - inhibits hormone-sensitive lipase
  5. Increases removal of lipids from VLDL and chylomicrons => into adipocyte
55
Q

What can the proglucagon molecule yield depending on how its cleaved?

A
  • GRPP
  • Glucagon
  • IP-1 and IP-2
  • GLP-1 and GLP-2
56
Q

What cleaves proglucagon at points to yield GRPP, glucagon, and the C-terminal fragment?

A

Proteases in the pancreatic alpha cells

57
Q

What cleaves proglucagon to yield GLP-1 and GLP-2?

58
Q

5 stimulators of glucagon secretion?

A
  • Drop in blood glucose
  • Rise in serum Ala and Arg
  • Cortisol
  • SNS stimulation
  • Exercise, stress
59
Q

2 inhibitors of glucagon secretion?

A
  • Rise in blood glucose
  • Somatostatin
60
Q

Glucagon - liver effects? (4)

A
  1. Increase glucose output to other tissues
  2. Increased beta-oxidation
  3. Increased ketogenesis
  4. Increased urea cycle activity
61
Q

Glucagon - adipose effect?

A

Stimulation of hormone-sensitive lipase

62
Q

What does hormone-sensitive lipase do?

A

Promotes lipolysis and release of FFAs

63
Q

Glucagon - muscle effect?

A

No direct effect

64
Q

High insulin/glucagon ratio?

A

Anabolic state - nutrient incorporation into peripheral tissue

65
Q

Low insulin/glucagon ratio?

A

Catabolic state - nutrient mobilization

66
Q

When are insulin and glucagon not inversely related?

A

Low carb, high protein diet

67
Q

Polypeptide hormone produced in pancreatic delta cells and GI tract?

A

Somatostatin

68
Q

What does somatostatin tend to decrease?

A

Both insulin and glucagon secretion

69
Q

Stimuli for release of somatostatin in pancreas and GIT? (2)

A
  • Stimulators of insulin release
  • GI hormones (Secretin, CCK)

BMS150 Post-MT2 (17 decks)

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