REB 9. Glucagon

Question 1

What is the function of glucagon?

Answer 1

Glucagon regulates blood glucose levels by stimulating breakdown of glycogen to glucose
- this opposes the effect of insulin

Question 2

What is the structure of glucagon and what is its precursor?

Answer 2

It is a polypeptide hormone (29 amino acids) and Proglucagon is its precursor

Question 3

In the pancreas, what converts proglucagon to glucagon?

Answer 3

Prohormone Convertase 2 (PC2)

Question 4

In the intestine, what converts proglucagon to glucagon-like peptide 1 and 2?

Answer 4

Prohormone Convertase 1/3 (PC1/3)

Question 5

What other hormones are created by proglucagon in the pancreas?

Answer 5

[1] glucagon
[2] glicentin-related pancreatic polypeptide (GRPP)
[3] intervening peptide 1 (IP1)
[4] major proglucagon fragment (MPGF)

Question 6

What are some other things that are created by proglucagon in the intestine?

Answer 6

[1] glucagon-like peptide 1 (GLP-1)
[2] glucagon-like peptide 2 (GLP-2)
[3] oxyntomodulin
[4] intervening peptide 2 (IP2)
[5] glicentin

Question 7

What is the process/steps that are involved in glucagon secretion?

Answer 7

[1] on hypoglycaemia, intracellular glucose concentration falls
[2] there is a reduction in glycolysis-generated ATP in the mitochondria of the cell (the ATP/ADP ratio decreases)
- glycolysis turns glucose into glucose-6-phosphate
[3] closure of ATP sensitive K+ channels (intracellular K+ concentration rises)
[4] this depolarizes the cell membrane, opens the voltage-dependent Ca2+ channels allowing the influx of Ca2+
[5] increase in intracellular Ca2+ concentration triggers secretion of glucagon through exocytosis

Question 8

What are some stimulating factors of glucagon secretion?

Answer 8

[1] Low Blood Glucose levels
E.g. to prevent hypoglycaemia
[2] Following a Protein Rich Meal
- counteracting insulin release after the meal
[3] in response to Epinephrine/Norepinephrine
- glucagon levels increased in anticipation of increased glucose use

Question 9

What are some inhibiting factors of glucagon secretion?

Answer 9

[1] high blood glucose
- you don’t want more glucose in body
[2] insulin (paracrinic effect)
- leads to glucose uptake (in presence of high glucose levels)

Question 10

What are the main metabolic effects of glucagon?

Answer 10

[1] Promotes Glycogenolysis
- promotes hepatic conversion of glycogen to glucose

[2] Promotes Gluconeogeneis
- stimulates de novo glucose synthesis

[3] Inhibits Glycolysis
- inhibits glucose breakdown

[4] Inhibits Glycogenesis
- inhibits glycogen formation

[5] Ketogenesis
- oxidation of fatty acids + formation of ketone bodies in adipose tissue

Question 11

Why is glucagon important for brain function and working muscle?

Answer 11

Glucagon is key in providing circulating glucose to brain function and for working muscle during exercise

Question 12

What is the mechanism of action of glucagon?

Answer 12

[1] activation of glucagon receptor
[2] 7-transmembrane GPCR is expressed in the liver (minor in kidneys + pancreas)
[3] stimulates adenylyl cyclase
[4] adenylyl cyclase stimulates cAMP
[5] cAMP activates protein kinase A
[6] PKA migrated to the nucleus and activates transcription factors promoting gene expression

Question 13

What is the Whipple’s Triad (hypoglycaemia symptoms)?

Answer 13

[1] Hypoglycaemic Symptoms

• Sympathetic Nervous Symptoms > Adrenergic (anxiety, tremor, sweating)
• Central Nervous System > Neuroglycopenic (cognitive and motor impairment, slurred speech, seizures, coma)

[2] Blood Glucose Levels < 50mg/dL

[3] Symptoms Resolving on Administration of Glucose

Question 14

What are the body’s main responses to low blood- glucose (hypoglycaemia) levels?

Answer 14

[1] pancreas starts secreting glucagon (and insulin production is stopped)

[2] the hypothalamus senses the low glucose and stimulates (a) epinephrine and (b) cortisol secretion from the adrenal gland

• epinephrine causes glycogen to be converted to glucose
• cortisol causes the body tissues to be less sensitive to insulin

Question 15

What are the 4 main types of hypoglycaemia? (just list them)

Answer 15

[1] Insulin-Induced
[2] Postprandial
[3] Fasting
[4] Ethanol-Induced

Question 16

What is the main cause (target group) of Insulin-Induced Hypoglycaemia? What is its treatment?

Answer 16

• patients with Type I diabetes (the injection of insulin leads to an excessive drop in glucose levels)

treatment:
[1] oral glucose (if patient conscious)
[2] glucagon intramuscular injection (if patient unconscious)

Question 17

What is the main cause of Postprandial Hypoglycaemia? What is its treatment?

Answer 17

• transient hypoglycaemia
• caused by exaggerated insulin release after a meal

symptoms: some mild adrenergic symptoms (anxiety, tremor, sweating)
treatment: plasma glucose returns back tonormal even if patient is not fed (eat less more frequently)

Question 18

What is the main cause of Fasting Hypoglycaemia? What are its symptoms? What serious problems can it be an indicator for?

Answer 18

• fasting hypoglycaemia occurs in those in whose body fails to maintain adequate levels of glucose
  symptoms: neuroglycopenic (confusion, seizures, coma)

indicator for:
[1] Pancreatic Tumour
- insulinoma, rare
[2] Adrenal Insufficiency
- cortisol, epinephrine
[3] Liver Damage 
- impaired gluconeogenesis

Question 19

What is the main cause/mechanism of Alcohol-Induced Hypoglycaemia?

Answer 19

[1] metabolism of alcohol leads to generation of excess NADH

[2] excess NADH diverts pyruvate and oxaloacetate away from gluconeogenesis

[3] increases risk of hypoglycaemia (in particular, those with depleted glycogen stores [i.e. irregular meals])