Insulin - Counter regulatory hormone

Question 1

What is the key role of insulin in controlling blood glucose levels

Answer 1

1, high glucose levels – removal of glucose from the blood (transport)

2. Synthesis of glycogen and triglycerides to store energy
3. Inhibition of processes that release glucose/fatty acids

Question 2

What is the main hormone that is used in fasting to control blood glucose levels

Answer 2

Glucaogn

Question 3

describe what metabolism is like during fasting

Answer 3

1. Low glucose levels –No glucose transport
2. Glycogen and triglycerides are not synthesised anymore
3. Processes that release glucose/fatty acids are not inhibited anymore

Question 4

describe the structure of glucagon

Answer 4

• 29 amino acids

- one chain only

Question 5

what islets of langhernas produce glucagon

Answer 5

alpha

Question 6

describe how synthesis of glucagon takes place

Answer 6

• Frist synthesised as a preproglucagon
• Broken down into a proglucagon
• This is then broken down into a glucagon

Question 7

name another hormone that comes from the same precursor as glucagon

Answer 7

GLP-1

Question 8

how low is blood glucose in order to do glucagon secretion

Answer 8

• Stimulated by low blood glucose concentration – normal fasting levels of glucose is 80-90mg/100ml

Question 9

what causes an increase in glucagon secretion

Answer 9

• Exercise - In exhaustive exercise blood concentration of glucagon increases four to five fold
  (increased circulating amino acids or β-adrenergic stimulation may play a role)

Question 10

what inhibits glucagon secretion

Answer 10

• inulin - it breaks down cAMP by phosphodiesterase enzyme

- somatostatin (produced by delta cells in the islet of langerhans)

Question 11

what are the effects of glucagon

Answer 11

 Increases glycogenolysis in the liver.
 Increased uptake of amino acids in the liver.
 Increases gluconeogenesis in the liver (amino acids, glycerol and lactate).
 Liver glycolysis is inhibited by inhibiting pyruvate kinase and PFK1.
 Increased lipolysis, glucagon activates hormone sensitive lipase (HSL).
 More ketogenesis is able to occur.

Question 12

how is glucagon receptor signalled

Answer 12

• The glucagon receptor is a G protein coupled receptor
• GPCRs contain 7 transmembrane domains are coupled to trimeric G proteins
• Dissociation of the trimer upon ligand binding to the receptor activates the signalling cascade
• In the absence of glucose, it is assembled in the trimeric form and the 3 subunits are joined together
• This activates adenylase cyclase and this activates cAMP
• The cAMP which is produced in this reaction triggers the cascade
• cAMP is produced and this activates PKA and then this increases phosphorylase kinase and activates the rest of the cascade causing glycogenolysis

Question 13

what is CPT1

Answer 13

 Important enzyme in the Beta oxidation of fatty acids into Acetyl-CoA.

Question 14

what inhibits CPT1 and what activates CPT1

Answer 14

 CPT1 is inhibited by insulin.

 It is activated by glucagon.

Question 15

what happens in prolonged glucagon

Answer 15

 Oxaloacetate replaces amino acids as the main source for gluconeogenesis.
 Acetyl-CoA is converted into acetoacetate (ketone) via HMG-CoA.
 Glucagon inhibits HMG-CoA to prevent excess cholesterol and TGA formation.
 But, glucagon increases ketogenesis.

Question 16

what does triglycerides break down into

Answer 16

glycerol and free fatty acids

- glycerol is used in gluconeogensis

Question 17

what does amlonyl CoA inhibit

Answer 17

• Malonyl-CoA inhibits transport of FFAs into mitochondria via CPT-1 therefore inhibiting β oxidation

Question 18

what is oxaloacate used int he liver by

Answer 18

• oxaloacetate is used by the liver as substrate for gluconeogensis

Question 19

what is excess acetyl-CoA converted into

Answer 19

• ketone bodies by the liver - keotgnesis

Question 20

what is ketogensis inhibited by

Answer 20

• inhibited by insulin and activated by glucagon

Question 21

name 3 catecholamines

Answer 21

• noradrenaline
• adrenaline
• dopamine

these are short term hormones

Question 22

where is adrenaline released from

Answer 22

Released from the medulla of the adrenal glands.

Question 23

what does adrenaline do

Answer 23

• Inhibits insulin secretion
• Stimulates glycogenolysis.
• Stimulates glucagon secretion.
• Increases lipolysis.

Question 24

what is adrenaline and dopamine synthesis from

Answer 24

• Monoamines are synthesised from phenylalanine and tyrosine

Question 25

when is adrenaline released

Answer 25

 Released during stress or hypoglycaemia, also part of fight or flight response.

Question 26

where are glucortoiciods produced

Answer 26

produced in the cortex

Question 27

name an example of glucoroctoids

Answer 27

cortisol | some steroids

Question 28

what causes the secretion of cortisol

Answer 28

 ACTH released in the anterior pituitary gland causes secretion of cortisol.

Question 29

is cortisol long term or short term

Answer 29

Long term = causes rapid utilisation of proteins and lipids.

Question 30

what are the actions of cortisol

Answer 30

- It enhances gluconeogenesis - It inhibits glucose uptake (and utilisation) - It stimulates muscle proteolysis - It stimulates adipose-tissue lipolysis

Question 31

what can cortisol also help

Answer 31

Cortisol is important in resisting stress and inflammation | Cortisol helps maintain blood pressure and it suppresses inflammation

Question 32

what can high cortisol levels cause

Answer 32

- Cushings sydrome | If levels of cortisol are elevated for a prolonged time they can induce proteolysis and muscle wasting

Question 33

cortisol usually does not....

Answer 33

Cortisol usually does not mobilise basic functional proteins such as muscle contractile proteins and proteins of neurons

Question 34

what do growth hormones do in - adipose tissue - liver - skeletal muscles

Answer 34

Adipose Tissue:  Increases lipolysis.  Reduces glucose uptake.  Reduces lipogenesis. Skeletal Muscle:  Reduces glucose uptake.  Increases lipoprotein lipase activity. Liver:  Increases VLDL secretion.  Increases production and uptake of HDL and LDLs.

Question 35

What do thyroid hormones do

Answer 35

 T3 and T4 increase the activity and number of mitochondria, increasing the rate of ATP synthesis.  Increase stimulation of carbohydrate metabolism: - Rapid glucose uptake. - Enhances glycolysis and gluconeogenesis. - Increase insulin secretion.  Increase stimulation of fat metabolism: - Lipids mobilised rapidly from adipose tissue. - Fatty acid concentration in blood increased.  Overall effect is to increase basal metabolic rate.

Question 36

what is more potent T3 or T4

Answer 36

- T3 is about 4 times more potent than T4 | - T3 is present in the blood in much smaller quantities and persists for a much shorter time

Question 37

what are incretins

Answer 37

- these are a group of gastrointestinal hormones

Question 38

name some examples of incretins

Answer 38

Glucagon-like peptide-1 (GLP-1) | Gastric inhibitory peptide

Question 39

what does GLP-1 do

Answer 39

- inhibits glucagon secretion and hepatic glucose production - slows gastric emptying - promotes satiety - augments glucose-induced inulin secretion - rests beta cell function - increases insulin biosynthesis - promotes B cell differentiation

Question 40

what is hypoglycaemia

Answer 40

any abnormally low plasma glucose concentration that exposes the subject to potential harm" with a proposed threshold plasma glucose value <70 mg/dL (<3.9 mmol/L)

Question 41

what cause cause hypoglycaemia

Answer 41

- can be caused by stimulation of glucose utilisation and inhibition of glucose release High insulin doses Alcohol excess (inhibition of gluconeogenesis) Insulinoma (A tumour of pancreatic β cells) Excessive exercise (Leading to increased glucose utilisation) Reactive hypoglycaemia (Excessive insulin secretion in response to a high carbohydrate meal in the pre-diabetic condition)

Question 42

what is a major combination of type I diabetes

Answer 42

- hypoglycaemia is a major combination of type I diabetes

Question 43

what are the symptoms of hypoglycaemia

Answer 43

Autonomic symptoms - Include trembling palpation, sweating, anxiety, hunger, tingling Neuroglycopenic symptom s - Including difficulty concentration, confusion, weakness, drowsiness, vision changes, difficulty speaking, dizziness, tiredness Severe - Confusion - Disorientation - Confusions - Fitting - Seizures - Loss of consciousness - Coma

Question 44

what is prolonged hypoglycaemia caused

Answer 44

- Growth hormone and cortisol are secreted – they decrease the rate of glucose utilisation by most cells converting to fat utilisation

Question 45

what are the consequences of hypoglycaemia

Answer 45

- Serious consequences related to neuroglycopaenia (shortage of glucose for the brain) - Prolonged and repeated hypoglycaemia may produce permanent brain damage - Loss of cognitive function, seizures and coma

Question 46

how many type 1 diabetes patients get reccurnet severe hypoglycaemia

Answer 46

Recurrent severe hypoglycaemia affects 1-3% of Type 1 diabetes patients, mostly adults having diabetes for > 10 years