8. Glucagon

Question 1

What are normal blood glucose levels?

Answer 1

2.9-7.1 mmol/L

Question 2

What type of hormone is glucagon?

Answer 2

Polypeptide

29 amino acids

Question 3

How is proglucagon converted to glucagon?

Answer 3

Proteolytic cleavage

Question 4

Where is proglucagon produced?

Answer 4

Pancreatic islet alpha cells

Intestinal enteroendocrine L cells

Question 5

What hormone converts proglucagon to glucagon in the pancreas?

Answer 5

Prohormone Convertase 2

PC2

Question 6

What process proglucagon in the intestine?

Answer 6

Prohormone convertase 1/3

Question 7

What is proglucagon broken into in the pancreas?

Answer 7

Glucagon
Glicentin-related pancreatic polypeptide (GRPP)
Intervening Peptide 1 (IP-1)
Major proglucagon fragment (MPGF)

Question 8

What is proglucagon broken into in the intestine?

Answer 8

Glucagon-like peptide 1
Glucagon-like peptide 2
Oxyntomodulin
Intervening peptide 2
Glicentin

Question 9

What are the events occuring up to glucagon secretion?

Answer 9

1. During hypoglycaemia intracellular glucose conc falls
2. Reduction in glycolysis-generated ATP in mitochondria of the cell
3. K+ leak channels close
4. Cell membrane depolarises, opens voltage gated Ca++ channels, influx of Ca++
5. Increased intracellular Ca++ triggers glucagon secretion through exocytosis

Question 10

What factors stimulate glucagon secretion?

Answer 10

Low blood glucose
After a protein rich meal
Response to epinephrine/norepinephrine

Question 11

What factors inhibit glucagon secretion?

Answer 11

High blood glucose

Insulin

Question 12

What are the metabolic effects of glucagon?

Answer 12

1. Promotes conversion of glycogen to glucose in the liver
2. Stimulates new glucose synthesis
3. Inhibits glucose breakdown
4. Inhibits glycogen formation
5. Oxidation of fatty acids and formation of ketone bodies in adipose tissue

Question 13

What type of receptor is a glucagon receptor?

Answer 13

GPCR

Question 14

What happens once a glucagon receptor is activated?

Answer 14

Stimulates adenylyl cyclase to produce cAMP
Activates protein kinase A
PKA migrates to nucleus and activates transcription factors promoting gene expression

Question 15

Which enzymes does glucagon increase the activity of?

Answer 15

Glycogen phosphorylase
Glucose 6-phosphatase
Fructose 2,6-bisphosphatase
PEP carboxylase
Transaminases

Question 16

Which enzymes does glucagon decrease the activity of?

Answer 16

Glycogen synthase
Phosphofructokinase
Pyruvate kinase
Acetyl CoA carboxylase
HMGCoA reductase

Question 17

What is Whipple’s Triad?

Answer 17

The three entities to a hypoglycaemic state:
Sympathetic nervous system and central nervous system symptoms
Blood glucose <50mg/dL
Symptoms resolve when glucose administered

Question 18

What is the body’s response to hypoglycaemia?

Answer 18

Pancreas secretes more glucagon

Hypothalamus senses low glucose and stimulates epinephrine and cortisol production

Question 19

What are 4 types of hypoglycaemia?

Answer 19

Insulin induced
Postprandial
Fasting
Ethanol-induced

Question 20

Why does alcohol cause hypoglycaemia?

Answer 20

Metabolism of alcohol makes an excess of NADH

Excess NADH diverts pyruvate and oxaloacetate away from gluconeogenesis