Part 3.1

Question 1

Actions following a calorie rich meal

Answer 1

Glucose clearance:
1) Uptake into liver for glycogenesis and lipogenesis
2) Support neural function
3) Lipogenesis and glycerol prod in adipose
4) Muscle cells glycogen replenish

Insulin:
1) released by pancreatic beta cells in response to glucose metabolism
2) required to drive glucose uptake by peripheral tissues

Question 2

Standard [Glucose] and during overnight fast, prolonged fast and a meal

Answer 2

Standard blood [glucose] = 5 mM

Overnight: blood [glucose] 3.9 - 4.9 mM

Prolonged: blood [glucose] = 3.3 - 3.9 mM

Fed: blood [glucose] = 6.8 - 7.4 mM
- Insulin secreted, no glucagon

Question 3

Lipid metabolism response to fed state

Protein metabolism response to fed state

Answer 3

↑ lipogenesis (TAG synthesis)
↓ lipoprotein lipase activity in endothelial cells (decreased nutrient absorption)
Decreased plasma glycerol and free FA

↑ AA uptake into cells
↑ protein synthesis
↓ protein catabolism
Decreased plasma AA

Question 4

Alpha vs. beta cells of the islets

Answer 4

Beta-cells: high [glucose] activated, releases insulin, stimulates glucose clearance and storage, lipogenesis, cell proliferation and growth

Alpha cells: low [glucose] activated, releases glucagon, stimulates glucose mobilization, gluconeogenesis and fat metabolism

Question 5

Brain response to insulin

Answer 5

↑ glycolysis, ↑ ATP production, ↑ satiety signaling

Question 6

Liver response to insulin

Answer 6

1) ↑ Glycogenesis: Glycogen synthase
2) ↑ Glycolysis: Glucokinase, PFK-1, PFK-2, PDH
3) ↑ Lipogenesis: ATP-citrate lyase (citrate –> acetyl coA), ACC, FA synthase, glucose-6-phosphate dehydrogenase (PPP)
4) ↑ Lipoprotein formation
5) ↑ cell proliferation/growth

1) ↓ Glycogenolysis: glycogen phosphorylase
2) ↓ Gluconeogenesis: PEP carboxykinase, FBPase-1, FBPase-2, glycogen phosphorylase

Question 7

Adipocyte response to insulin

Answer 7

1) ↑ Fat synthesis: ACC and FAS
2) ↑ TAG biosynthesis
3) ↑ Lipoprotein lipase
4) ↑ cell proliferation and growth
5) ↑ GLUT4 expression

1) ↓ lipolysis

Question 8

Muscle response to insulin

Answer 8

1) ↑ glycogenesis: glycogen synthase
2) Glycolysis: hexokinase, PFK-1, GLUTs, lactate dehydrogenase (LDH) and PDH

Question 9

Insulin synthesis pathway

Answer 9

1) [Glucose] ~7 mM is stimulating response element that encodes gene for insulin

2) mRNA is bound by signal peptide mid translation and then by SRP

3) SRP recognizes and binds ER membrane receptor and translocan (sec61) opens

4) Translation continues and SRP is released into cytoplasm

5) Signal peptidase degrades signal peptide

6) Proinsulin is oxidized inside ER and disulfide bridge can form

Question 10

Signal peptide

SRP

Answer 10

specific sequence of AA on N terminus which tells ribosome to stop (AKA stop sequence) until it gets to the surface of the ER

Signal recognition particle - directs signal peptide to the ER to finish translation
- Binds receptor on surface of ER and allows translocan (sec61) to open and feeds translated peptide through

Question 11

Insulin secretion pathway in pancreatic beta cells

Answer 11

1)↑ [glucose] after meal is sensed by beta cells via GLUT 2 transporters

2) Glycolysis and Krebs cycle occur to produce ATP

3) ↑ [ATP]/[ADP] ratio, ATP inhibits K channel, depolarizing membrane

4) ∆ in membrane potential opens voltage gated Ca2+ channel, increasing cytoplasmic Ca2+

5) Ca2+ acts as messenger to trigger fusion of insulin filled vesicles for release into bloodstream

Question 12

Insulin gene TF recruited in response to high [glucose]

Answer 12

Set7/9, p300, PRDX-1

Question 13

What state is glycogen synthase active?

What state is glycogen phosphorylase active?

Answer 13

Glycogen synthase:
active when de-phosphorylated
inactive when phosphorylated

Glycogen phosphorylase:
active when phosphorylated
inactive when de-phosphorylated

opposites!

Question 14

Activators and inhibitors of glycogen synthesis in the liver

Activators and inhibitors of glycogenolysis in the liver

Answer 14

Glycogenesis:
Activators: insulin, Glucose-6-phosphate
Inactivators: glucagon, epinephrine, Ca2+

Glycogenolysis:
Activators: glucagon, epinephrine, Ca2+
Inhibitors: glucose, insulin, glucose-6-phosphate, ATP

Question 15

Activators and inhibitors of glycogen synthesis in the muscle

Activators and inhibitors of glycogenolysis in the muscle

Answer 15

Glycogenesis:
Activators: insulin, Glucose-6-phosphate
Inactivators: Epinephrine

Glycogenolysis:
Activators: epinephrine, AMP, Ca2+
Inhibitors: insulin, glucose-6-phosphate, ATP