A. PANCREAS

Question 1

what cells of islets of Langerhans secrete insulin

Answer 1

beta-cells (biggest proportion of total human islet cells)

Question 2

what cells of islets of Langerhans secrete glucagon

Answer 2

alpha-cells

Question 3

what cells of islets of Langerhans secrete somatostatin

Answer 3

delta-cells

Question 4

what cells of islets of Langerhans secrete pancreatic polypeptide

Answer 4

PP-cells

Question 5

what cells of islets of Langerhans secrete ghrelin

Answer 5

epsilon cells

Question 6

what is involved in exocrine system of pancreas

Answer 6

secretes digestive enzymes which break down carbohydrates, proteins and lipids in chyme

Question 7

what is involved in endocrine system of pancreas

Answer 7

islets of Langerhans involved in glucose homeostasis

Question 8

what are islets of langerhans

Answer 8

endocrine cells in clusters scattered throughout the pancreas
(1-2% of the total pancreatic mass but receives 10% of blood supply)

Question 9

why does insulin have a short half-life

Answer 9

there are proteases in the plasma

Question 10

what is the structure of insulin

Answer 10

A-chain of 21 amino acids
B-chain of 30 amino acids
C-peptide of 35 amino acids is packaged with insulin in the secretory granules when proinsulin in humans (31 aa cleaved)
there are 2 intermolecular disulphide bonds and 1 intramolecular disulphide bond
therefore human insulin is 86 amino acids

Question 11

insulin biosynthesis

Answer 11

• insulin gene transcription and translation
• preproinsulin synthesis (cleavage of signal sequence)
• proinsulin transfer to insulin through cleavage of C-peptide which makes it less soluble
• insulin precipitates to 2 ZN: 6 insulin to form a dense crystalloid core in secretary granules and hence lots can be packaged into granule
• exocytosis involving calcium ions and ATP

Question 12

how is insulin release regulated

Answer 12

glucose from food causes beta-cells to release insulin

Question 13

how does low glucose levels cause low basal insulin secretion

Answer 13

• glucose metabolised in cell
• causes an increased ATP:ADP ratio
• ATP-sensitive K channels are open

Question 14

how does glucose levels >5mmol/L cause insulin secretion

Answer 14

• glucose metabolised in cell
• causes an increased ATP:ADP ratio
• ATP-sensitive K channels are closed causing a decrease in K leaving cells
• there is membrane depolarisation which causes voltage gated calcium channels to open and there is an an increase in intracellular calcium levels
• there is increased exocytosis of secretory vesicles and hence enhanced insulin release

Question 15

when are gut hormones (incretins) released and what do they do

Answer 15

when there is a rise in blood glucose from meals and they prepare the body to secrete insulin

Question 16

what causes an increase in insulin release

Answer 16

glucagon released from alpha-cell

Question 17

what inhibits insulin release

Answer 17

somatostatin released from delta-cell inhibits alpha and beta-cells

Question 18

how does the parasympathetic nervous system muscarinic receptors affect beta cells

Answer 18

stimulates insulin release

Question 19

how does the sympathetic nervous system alpha2-ARs and circulating Adr affect beta cells

Answer 19

inhibit insulin release

Question 20

how do beta-ARs affect beta cells

Answer 20

stimulate insulin release

Question 21

what receptors do beta cells express

Answer 21

alpha-2 and beta adrenoceptors
more alpha-2 than beta
hence more activation of alpha-2 which is inhibition of insulin release

Question 22

what does insulin promote

Answer 22

• growth and development
• cellular uptake of potassium via sodium/potassium ATPase pump
• uptake and utilisation of glucose in skeletal muscle and adipose tissue
• fuel storage (anabolic) as increases rate of synthesis and storage of energy reserves (glycogen and fats) and of proteins

Question 23

how does blood glucose affect the liver

Answer 23

• increased glycogen synthesis
• decreased glycogen breakdown
• decreased gluconeogenesis (glucose production from intermediates)

Question 24

how does glucose affect the muscle

Answer 24

• increased glucose uptake via GLUT-4 receptor
• increased protein synthesis
• decreased protein breakdown

Question 25

how does glucose affect adipose tissue

Answer 25

- increased glucose uptake via GLUT-4 - increased lipogenesis - decreased lipolysis

Question 26

how do tyrosine kinase receptors work when insulin attach

Answer 26

- has enzyme activity activated by hormone binding - Tyrosine kinase phosphorylates target protein (receptor itself or other proteins) - adapter proteins then produce multiple signals including gene expression changes

Question 27

what adaptor proteins are attracted to phosphorylated tyrosine kinase when insulin binds - METABOLIC SIGNAL

Answer 27

IRS and it gets phosphorylated PI 3-kinase catalyses PIP2 to PIP3 PDK1/2 activated PKB/Akt activated which causes glucose uptake, protein synthesis, glycogen synthesis and anti-lipolysis

Question 28

what adapter proteins are attracted to phosphorylated tyrosine kinase when insulin binds - GROWTH SIGNAL

Answer 28

- Shc and gets phosphorylated - Grb2 - SOS which leads to MAPK which causes cell survival and cell proliferation

Question 29

what is glucagon

Answer 29

a peptide hormone and has the opposite actions to those of insulin

Question 30

where is glucagon synthesised

Answer 30

islet alpha-cells

Question 31

when is glucagon released

Answer 31

stimulated by low blood glucose (<3.5mmol/L) (para- and sympathetic nervous systems and amino acids)

Question 32

when is glucagon release inhibited

Answer 32

by high blood glucose, insulin and somatostatin (paracrine)

Question 33

what is the main action of glucagon

Answer 33

raise blood glucose by: - stimulating hepatic glycogenolysis - stimulating hepatic gluconeogenesis - stimulating lipolysis (intermediates for gluconeogenesis)

Question 34

how to glucagon and insulin work to decrease blood glucose to normal

Answer 34

decreased glucagon production and increased insulin production

Question 35

how to glucagon and insulin work to increase blood glucose to normal

Answer 35

increased glucagon production and decreased insulin production

Question 36

what is somatostatin

Answer 36

a peptide hormone

Question 37

where is somatostatin synthesised

Answer 37

islet delta-cells and also in CNS and GIT

Question 38

what effects does somatostatin have

Answer 38

inhibits glucagon and insulin secretion by paracrine mechanism

Question 39

what is normal blood glucose range

Answer 39

4-8mmol/L

Question 40

what happens when glucose is raised

Answer 40

insulin released to stimulate increased glucose utilisation and uptake and hence lower levels (also promotes storage of fat, glycogen and protein - anabolic)

Question 41

what happens when glucose gets too low

Answer 41

glucagon, adrenaline, growth hormone and cortisol cause increased glucose production (glycogenolysis and gluconeogenesis) to increase levels

Question 42

when is adrenaline used

Answer 42

to provide energy for emergencies and exercise (if have severe hypoglycaemia)

Question 43

when is cortisol used

Answer 43

for mobilisation of fuels during adaptation to stress (if have prolonged hypoglycaemia)

Question 44

when is growth hormone used

Answer 44

to promote growth (if have prolonged hypoglycaemia)

Question 45

what disease is caused by chronic hyperglycaemia

Answer 45

diabetes mellitus