Glucagon and Insulin

Question 1

What is the pancreas divided into ?

Answer 1

An exocrine portion (acinar and duct tissue) and an endocrine portion (islets of Langerhans)

Question 2

What does the exocrine glands and endocrine glands produce?

Answer 2

Exocrine glands: digestive enzymes, etc

Endocrine glands: hormones

Question 3

What is the structure of pancreatic islets of Langerhans?

Answer 3

The beta-cells are situated in the centre of the islets with the other cells in the periphery

Question 4

What stimulates islets of langerhans ?

Answer 4

The islets are highly innervated by the sympathetic and parasympathetic nervous system and have a high blood flow so the cells are ideally placed to sense the nutrient composition of the
blood

Question 5

What do beta cells and alpha cells secrete ?

Answer 5

• Beta cells secrete insulin

- Alpha cells secrete glucagon

Question 6

What chain is Glucagon and where is it made in ?

Answer 6

Glucagon is a single chain peptide (29aa) made in the pancreatic α cells

Question 7

What are both Glucagon and glucagon-like peptides derived from ?

Answer 7

Proglucagon: tissue-specific proteases determine which product is produced by which cells

Question 8

Besides insulin and glucagon, there are many other other signals that regulate food
intake, including a complex range of peptides secreted from the GI tract such as ?

Answer 8

• Cholecystokinin

- Glucagon-like peptide 1 (GLP-1)

Question 9

What is Cholecystokinin (CCK)?

Answer 9

This is a family of small peptide hormones secreted by cells of the intestine following a meal. CCK binds to its receptor in nerve cells,
causing increased feelings of satiety via the brain

Question 10

What is Glucagon-like peptide 1 (GLP-1) ?

Answer 10

This is a 30 amino acid
hormone secreted by the L cells of the intestine. Once bound to its receptor, GLP-1 induces feelings of satiety in the brain and potentiates insulin secretion while inhibiting glucagon secretion

Question 11

What is low-high blood glucose a major factor in ?

Answer 11

Stimulating/inhibiting glucagon secretion

Question 12

What also has an affect on secretion of glucagon secretion ?

Answer 12

A range of gut peptides and hormones, notably adrenaline

Question 13

What is the mechanism of glucagon action via cAMP ?

Answer 13

• Glucagon binds to the glucagon receptor in liver and
  adipose tissue (only)
• This activates the Gαs G protein, which in turn activates adenylate cyclase
• AC synthesises cAMP
• cAMP activates protein kinase A (PKA)
• PKA phosphorylates on ser/thr residues:
  Synthesis: OFF
  Breakdown: ON

Question 14

What pathways does the metabolic effect of glucagon generally inhibit and stimulate?

Answer 14

• Inhibits anabolic pathways (build larger molecules from smaller oner, which requires energy)
• Stimulates catabolic pathways (release energy by breaking down larger molecules)

Question 15

What does glucagon inhibit ?

Answer 15

Inhibits glycolysis in most tissues

Question 16

What is the effect of glucagon on cardiac stimulation ?

Answer 16

Increases contractility, little effect on rate

Question 17

What is the effect of glucagon on insulin ?

Answer 17

To stimulate insulin secretion from the islet beta cells

Question 18

Why does glucagon not function in the skeletal muscle?

Answer 18

As there are no glucagon receptors

Question 19

What is the key regulatory enzyme in glycolysis ?

Answer 19

Phosphofructokinase-1

Question 20

What is the key regulatory enzyme in gluconeogenesis?

Answer 20

Fructose-2,6-bisphosphatase

Question 21

What is used for glycogen regulation ?

Answer 21

Phosphorylase kinase and glycogen synthase

Question 22

What is downstream of insulin (so antagonising insulin-induced effects) ?

Answer 22

Protein Phosphatase (PP1)

Question 23

Explain the steps of Insulin biosynthesis ?

Answer 23

• Insulin mRNA goes to ribosomes where it is processed into preproinsulin (11.5kDa)
• Preproinsulin contains A and B chains and a signal peptide
  which allows it to be secreted into the cisternae of the rER.
• Preproinsulin moves from ER to Golgi where signal peptide
  cleaved off, producing pro-insulin (9kDA): has to fold
  precisely due to disulphide bridges
• Dipeptide sites between A and B chain cleaved and
  connecting C peptide is cut out
• This reduces solubility: forms microcrystals with zinc and
  packaged into vesicles for secretion

Question 24

How do you stain immature secretory vesicles ?

Answer 24

Stain with the proinsulin
antibody, but not with the
insulin antibody

Question 25

How do you stain mature secretory vesicles ?

Answer 25

Stain with insulin antibody,
but not with proinsulin
antibody

Question 26

What inhibits Insulin release?

Answer 26

• Mannoheptulose

- Respiratory chain inhibitors

Question 27

Explain glucose regulation of insulin secretion ?

Answer 27

• Glucose (>7mM) enters β cells via GLUT2
• Glucose enters glycolysis, resulting in a rise in ATP
• ATP binds to ATP-gated K+ channels.
• K+ channels close, depolarise the plasma membrane
• Depolarisation triggers opening of voltage-gated Ca2+ channels
• Increased Ca2+ in cytosol triggers release of insulin by exocytosis

Question 28

Explain the metabolic actions of insulin (via RTK) ?

Answer 28

• Many effects mediated by dephosphorylation of key enzymes by PP1, and increased
  breakdown of cAMP by stimulating phosphodiesterase
• Generally stimulating anabolic pathways and inhibiting catabolic ones

Question 29

What is the key role of increasing GLUT4 transporters on muscle and adipose cell
membranes to ?

Answer 29

Increase glucose uptake

Question 30

What is Glucokinase used for?

Answer 30

• Glucose sensor

- Enables glycolysis

Question 31

What catalyses the key

conversion of pyruvate to acetyl-CoA ?

Answer 31

Pyruvate dehydrogenase