17 - Insulin and Glucagon

Question 1

GLuconeogenesis, glycogenolysis and ketogenesis are ____ by insulin and ____ by glucagon

Answer 1

Downregulated by insulin and upregulated by glucagon

Question 2

What are acinar cells?

Answer 2

Exocrine cells in the pancreas that secrete pancreatic hormones into the duct and gastrointestinal tract

Question 3

What do delta cells in islets of Langerhans do?

Answer 3

Secrete somatostatin into blood stream.

Somatostatin inhibits glucagon AND insulin secretion

Question 4

Describe the synthesis and secretion of insulin

Answer 4

1. Synthesis in ER
2. Cleavage of signal peptide sequence
3. Transport of proinsulin into golgi
4. Two endoproteases cut out C peptide
5. Carboxypeptidase E cuts the last two Arg residues off the B chain to produce mature insulin (in the golgi)

Question 5

How does epinephrine effect insulin and glucagon

Answer 5

Insulin: inhibited

Glucagon: stimulated

Glucagon secretion is also inhibited by glucose and insulin

Question 6

how do amino acids affect insulin and glucagon? Why?

Answer 6

IN the presence of glucose, amino acids upregulate insulin secretion and affect glucagon secretion only to a small extent

In the absence of glucose, amino acids upregulate glucagon secretion.

• In the fasting state, amino acids are present due to breakdown of proteins, but glucose is absent, so glucagon is activated to signal that amino acids must be used for gluconeogenesis in the liver
• Glucagon stimulation by amino acids also prevents a high protein meal with few carbohydrates causing a rise in insulin and hypoglycemia

Question 7

How does glucose trigger insulin secretion?

Answer 7

• Enters beta cell and becomes pyruvate through glycolysis
• Pyruvate enters TCA cycle and produces ATP
• ATP opens potassium (K) channels (K exits), depolarizing the cell and causing an influx of calcium ion
• Calcium ion causes the release of secretory granules (think like NT)

Question 8

What type of receptor is insulin receptor? Give steps of signalling and short term effects.

Answer 8

Tyrosine kinase

1. Insulin binds
2. Tyrosine phosphorylation of the receptor creates new epitopes
3. Adaptor protein (Shc/Grb2, IRS) bind to phosphotyrosine
4. IRS activates P13-kinase
5. P13 kinase activation lealds to phosphorylation and activation of protein kinase B

Short term effects

6. PKB phosphorylates and inactivates glycogen synthase kinase
7. Inactivated GSK3 stops inactivating glycogen synthase
8. GLycogen synthesis is activated

Over the long term, activation of Ras leads to MAP kinase cascade, causing transcription factor phosphorylation/activation and gene transcription

Question 9

Which glucose transporters are and are not regulated by insulin?

Answer 9

GLUT2: Liver, pancreas, kidney: not regulated by insulin

GLUT4: muscle and adipose: expression and localization regulated by insulin

Activation of insulin receptor causes translocation of GLUT4 translocation to membrane to increase glucose uptake in muscles and adipocytes (and remove glucose from blood)

Question 10

What type of receptor is glucagon receptor?

Answer 10

G protein coupled receptor

- Liberated g protein binds adenylate cyclase and promotes cAMP synthesis from ATP

Question 11

What are the short term and long term effects of glucagon?

Answer 11

SHort term
- Glycogen mobilized through sequential enzyme phosphorylation

Long term

• Phosphorylation of CREB by PKA leading to gene expression of PEPCK (RLSE for gluconeogenesis)
• CREB-CBP complex