insulin secretion and action

Question 1

what is the normal range for fasting glucose?

Answer 1

3.5-5.5mmol/L

Question 2

what are the main roles of insulin?

Answer 2

• High glucose levels -Removal of glucose from blood (transport)
• Synthesis of glycogen and triglycerides (to store energy)
• Inhibition of processes that release glucose/fatty acids

Question 3

what happens in low glucose when insulin secretion is inhibited?

Answer 3

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

Question 4

what is the main hormone controlling blood glucose levels during fasting?

Answer 4

glucagon

Question 5

how many amino acids in a glucagon peptide?

Answer 5

29

Question 6

describe how the synthesis of glucagon occurs

Answer 6

preproglucagon –> proglucagon –> pancreatic a-cells

or proglucagon can also undergo post-translational processes –> L-intestinal cells in the brain

Question 7

what stimulates glucagon secretion?

Answer 7

• Low blood glucose levels – normal fasting levels of glucose: 80-90mg/100ml
• Increased blood amino acids – especially alanine and arginine
• Exercise – in exhaustive exercise blood conc of glucagon increases 4.5 fold
• Increase in intracellular calcium triggers an increase in glucagon

Question 8

what inhibits glucagon secretion?

Answer 8

insulin

somatostatin

Question 9

what type of receptor is the glucagon receptor?

Answer 9

GPCR - 7 transmembrane domains

Question 10

explain how glucagon activates the receptor?

Answer 10

• Dissociation of the trimer upon ligand binding to the receptor activates the signalling cascade - In the absence of glucose, trimer is assembled
• When glucagon binds, a-subunit dissociates and can activate a cyclase - makes cAMP
• cAMP triggers activation of the cascade
• Activates PKA which activates phosphorylase
• Only when the ligand binds, there’s production of cAMP

Question 11

how can insulin regulate glucagon signalling?

Answer 11

• Further regulation by insulin: insulin can switch glucagon-dependent signalling off
• Insulin can break down cAMP to 5’ AMP by activating phosphodiesterase

Question 12

describe metabolism during fasting?

Answer 12

• Reduced glucose levels – no insulin secretion
• Glycogenolysis isn’t inhibited
• No glucose transport
• Glycogen and triglycerides are not synthesised anymore
• Processes that release glucose/fatty acids are NOT INHIBITED
• Liver releases glucose into the bloodstream
• Gluconeogenesis – synthesis of new glucose – is stimulated by glucagon in the liver
• Lipolysis is not inhibited by insulin

Question 13

how does glucagon increase gluconeogenesis and inhibit glycolysis in the liver?

Answer 13

• Increases amino acid uptake by liver cells
• Inhibition of PFK-1 (mediated by cAMP/PKA)
• Inhibition of pyruvate kinase (mediated by cAMP/PKA)

Question 14

what is lipolysis?

Answer 14

breaking down of triglycerides to FFAs and glycerol

Question 15

what effect does HSL have on lipolysis?

Answer 15

increases lipolysis

Question 16

what inhibits and activates HSL?

Answer 16

HSL inhibited by insulin and activated by glucagon/PKA

Question 17

what effect does malonyl-CoA have on beta oxidation?

Answer 17

• Malonyl-CoA inhibits transport of FFAs into the mitochondria by CPT-1 therefore inhibiting B-oxidation

Question 18

what effect does glucagon have on CPT-1?

Answer 18

stimulates it

Question 19

how do ketone bodies form during fasting?

Answer 19

Accumulation of Acetyl-CoA that can’t enter TCA cycle is converted into KETONE BODIES

Question 20

when are catecholamines released?

Answer 20

Short term stress response - Released in response to stress and hypoglycaemia

Question 21

what are catecholamines?

Answer 21

Monoamines synthesised from phenylalanine and tyrosine

Question 22

what effect do catecholamines have?

Answer 22

• Increase HR and BP, causes liver to convert glycogen to glucose, dilation of bronchioles etc

Question 23

which cells secrete glucocorticoids and other steroids?

Answer 23

cortex cells

Question 24

how are cortex cells adapted for steroid hormone synthesis?

Answer 24

have many LDL receptors which enables cholesterol uptake

Question 25

what stimulates cortisol release?

Answer 25

secreted in response to adrenocorticotropic hormone (ACTH) from the pituitary - -ve feedback loop

Question 26

what effects do cortisol have on metabolism?

Answer 26

* Enhances gluconeogenesis * Inhibits glucose uptake and utilisation * Stimulates muscle proteolysis * Stimulates adipose-tissue lipolysis  rapid mobilisation of amino acids and fatty acids from cellular stores

Question 27

what is the role of cortisol in stress and inflammation?

Answer 27

* Cortisol is important in resisting stress and inflammation e.g. from trauma, infection, intense heat or cold, surgery or almost any debilitating disease * Helps maintain BP and it supresses inflammation

Question 28

what can happen if cortisol levels are elevated for a prolonged time?

Answer 28

can induce proteolysis and muscle wasting

Question 29

what are thyroxine (T4) and Triiodothyronine (T3) ?

Answer 29

iodinated thryonines

Question 30

what do T3 and T4 do?

Answer 30

• Activate nuclear receptors and transcription of large number of genes

Question 31

which is more potent? T3 or T4?

Answer 31

T3 is about 4 times more potent than T4

Question 32

which is present in smaller quantities - T3 or T4?

Answer 32

T3

Question 33

what are the metabolic actions of thyroid hormones?

Answer 33

- increase in the number and activity of the mitochondria - stimulation of carbohydrate metabolism - stimulation of fat metabolism - leads to increased basal metabolic rate

Question 34

how do thyroid hormones stimulate carbohydrate metabolism?

Answer 34

o Rapid glucose uptake o Enhanced glycolysis and gluconeogenesis o Increased insulin secretion

Question 35

how is fat metabolism stimulated?

Answer 35

o Lipid mobilised rapidly from fat tissue | o Increased fatty acids concentration in the plasma

Question 36

what are incretins?

Answer 36

group of GI hormones

Question 37

what are the functions of GLP-1?

Answer 37

o Inhibits glucagon secretion and hepatic glucose production o Augments glucose-induced insulin secretion o Slows gastric e,ptying o Promotes satiety o Increases insulin biosynthesis o Promotes B-cell differentiation

Question 38

what can cause hypoglycaemia?

Answer 38

o High insulin doses o Alcohol excess – inhibits gluconeogenesis o Insulinoma – tumour of pancreatic B cells o Excessive exercise – leading to increased glucose utilisation o Reactive hypoglycaemia – excessive insulin secretion in response to a high carbohydrate meal in pre-diabetic condition

Question 39

what are symptoms of hypoglycaemia?

Answer 39

* Confusion, disorientation, convulsion, fitting, seizures, loss of consciousness, coma * Autonomic symptoms * Neuroglycopaenic symtpoms; difficulty concentrating, confusion, weakness, drowsiness, vision changes, difficulty speaking, dizziness, tiredness * Autonomic symptoms; Trembling, palpitation, sweating, anxiety, hunger, tingling

Question 40

what is secreted in prolonged hypoglycaemia?

Answer 40

• Growth hormone and cortisol are secreted – decrease rate of glucose utilisation

Question 41

what are the consequences of prolonged hypoglycaemia?

Answer 41

o Neuroglycopaenia – shortage of glucose for the brain o Prolonged and repeated hypoglycaemia may produce permanent brain damage o Loss of cognitive function, seizures and coma

Question 42

what can cause severe hypoglycaemia?

Answer 42

• Can occur in patients using blood glucose lowering medication or prandial glucose regulators as a result of; o Missed or delayed meal o Overdose medication o Exercise (without adjustment in medication) o Alcohol assumption