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
2
Q
Islet cells are a rich ____ supply
A
Capillary
3
Q
Blood flow in the islet cell?
A
From the center of the islet cell to the periphery
4
Q
Cell type making up 70% of pancreatic islet?
A
Beta cell
5
Q
Cell type making up 20% of pancreatic islet?
A
Alpha cell
6
Q
Cell type making up 5-10% of pancreatic islet?
A
Delta cell
7
Q
Hormone secreted by alpha cell?
A
Glucagon
8
Q
Hormone secreted by beta cell?
A
Insulin
9
Q
Hormone secreted by delta cell?
A
Somatostatin
10
Q
Hormone secreted by PP cell?
A
Pancreatic polypeptide
11
Q
General functions of alpha cell? (2)
A
- Increase blood glucose
- Make stored energy available
12
Q
General functions of beta cell? (2)
A
- Decrease blood glucose
- Cause entry of glucose into cells
13
Q
General function of delta cells?
A
Inhibits release of other islet hormones
14
Q
What kind of feedback loop is glucose homeostasis?
A
Negative feedback loop
15
Q
What happens if glucose drops under 3 mmol/L?
A
- Insulin secretion rapidly drops
- Epinephrine and glucagon secretion increase
16
Q
Why is hypoglycemia immediately much more harmful than hyperglycemia?
A
Multiple hormones increase blood glucose, but only one (insulin) drops it
17
Q
Where in the beta cell does insulin synthesis take place?
A
Islets of Langerhans
18
Q
Insulin transcription
A
Transcription of insulin gene (INS) into mRNA in beta-cell nucleus
19
Q
Insulin mRNA processing (3)
A
- Capping
- Splicing
- Polyadenylation
20
Q
Insulin translation (2)
A
- mRNA exits nucleus => cytoplasm and binds to ribosomes
- Ribosomes assemble polypeptide chain
21
Q
What is the polypeptide chain that is synthesized by the ribosome in the beta cell called?
A
Pro-insulin
22
Q
What domains does pro-insulin contain? (3)
A
- A chain
- B chain
- Connecting C-peptide
23
Q
What happens as the proinsulin polypeptide elongates?
A
Folds into a 3D structure
24
Q
Where does proinsulin undergo post-translational modification?
A
Within the ER and Golgi
25
What happens during pro-insulin processing?
Cleavage of C-peptide = mature insulin + C-peptide
26
Once processed, mature insulin molecules are packaged into what?
Secretory vesicles
27
What are the enzymes and proteins in secretory vesicles necessary for?
Regulation of insulin secretion
28
What does a rise in glucose levels trigger?
Signalling pathway triggering the fusion of insulin containing vesicles with the cell membrane => release insulin into bloodstream
29
How does insulin circulate in the bloodstream?
Unbound
30
Enzyme that degrades insulin? Where is it found?
- Insulinase
- In the liver, kidneys, and other tissues
31
What can you measure to determine how much endogenous insulin is secreted by diabetics?
C-peptide since released alongside insulin
32
Blood glucose concentrations change the ratio of ADP:ATP, what does this change?
Membrane potential by changing potassium conductance
33
What happens when insulin binds to its receptor? (2)
- Dimerization
- Activates Tyr-K activity (autophosphorylation)
34
Key GPCR pathways in insulin receptor activation? (2)
- PI3K pathway => Akt and mTOR activation
- Ras => Raf => MAPK
35
What happens to cells that are chronically exposed to high levels of insulin?
Receptor desensitization
36
What is receptor desensitization? (2)
- Reduce number of insulin receptors expressed
- Down-regulates some signaling pathways distal to receptor activation
37
What nutrients stimulate insulin secretion? (3)
- Glucose (major)
- Amino acids (Arg, Lys)
- FFAs
38
What hormonal signals stimulate insulin secretion?
- CCK, GIP = incretins
- Parasympathetic innervation
- GH
39
What hormones inhibit insulin secretion? (3)
- Somatostatin
- Epinephrine
- Leptin
40
Where are incretins released from?
The intestines
41
Glucose travels in what direction along its concentration gradient?
Down
42
Why can’t glucose molecules freely diffuse through cell membranes?
Hydrophilic nature
43
Primary facilitators of glucose transport?
GLUT family of proteins
44
Where is GLUT1 found? What does it ensure?
- Brain
- RBCs
- Placenta
- Ensures basal glucose uptake
45
Where is GLUT2 found? What does it ensure?
- Liver
- Pancreas
- Kidneys
- Participates in glucose sensing and hepatic glucose uptake
46
Where is GLUT3 found? What does it ensure?
- Neurons
- Glucose reuptake in the brain
47
Where is GLUT4 found? What does it ensure?
- Skeletal muscle
- Adipose tissue
- Insulin-sensitive and has major role in postprandial glucose uptake
48
Glucose transport mechanism?
Facilitated diffusion = conformational change
49
Insulin-independent glucose transporters? Where are they?
- SGLT-1 and SGLT-2: intestine and kidneys
- GLUT-1 and GLUT-3: wide distribution
- GLUT-2: liver and pancreas
50
Insulin-dependent glucose transporters? Where are they?
- GLUT-4
- Skeletal and cardiac muscles and adipose tissue
51
What accounts for roughly 80% of insulin-mediated glucose uptake?
Skeletal muscle
52
Insulin - Liver effects? (5)
1. Increased glucose uptake from bloodstream
2. Increased glucose use
3. Increased FA and VLDL synthesis
4. Decreased ketogenesis
5. Increased protein synthesis
53
Insulin - Muscle effects? (4)
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
Insulin - adipose effects? (5)
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
What can the proglucagon molecule yield depending on how its cleaved?
- GRPP
- Glucagon
- IP-1 and IP-2
- GLP-1 and GLP-2
56
What cleaves proglucagon at points to yield GRPP, glucagon, and the C-terminal fragment?
Proteases in the pancreatic alpha cells
57
What cleaves proglucagon to yield GLP-1 and GLP-2?
Incretins
58
5 stimulators of glucagon secretion?
- Drop in blood glucose
- Rise in serum Ala and Arg
- Cortisol
- SNS stimulation
- Exercise, stress
59
2 inhibitors of glucagon secretion?
- Rise in blood glucose
- Somatostatin
60
Glucagon - liver effects? (4)
1. Increase glucose output to other tissues
2. Increased beta-oxidation
3. Increased ketogenesis
4. Increased urea cycle activity
61
Glucagon - adipose effect?
Stimulation of hormone-sensitive lipase
62
What does hormone-sensitive lipase do?
Promotes lipolysis and release of FFAs
63
Glucagon - muscle effect?
No direct effect
64
High insulin/glucagon ratio?
Anabolic state - nutrient incorporation into peripheral tissue
65
Low insulin/glucagon ratio?
Catabolic state - nutrient mobilization
66
When are insulin and glucagon not inversely related?
Low carb, high protein diet
67
Polypeptide hormone produced in pancreatic delta cells and GI tract?
Somatostatin
68
What does somatostatin tend to decrease?
Both insulin and glucagon secretion
69
Stimuli for release of somatostatin in pancreas and GIT? (2)
- Stimulators of insulin release
- GI hormones (Secretin, CCK)
