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ENDOCRINE > A. PANCREAS > Flashcards

A. PANCREAS Flashcards

1
Q

what cells of islets of Langerhans secrete insulin

A

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

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2
Q

what cells of islets of Langerhans secrete glucagon

A

alpha-cells

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3
Q

what cells of islets of Langerhans secrete somatostatin

A

delta-cells

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4
Q

what cells of islets of Langerhans secrete pancreatic polypeptide

A

PP-cells

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5
Q

what cells of islets of Langerhans secrete ghrelin

A

epsilon cells

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6
Q

what is involved in exocrine system of pancreas

A

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

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7
Q

what is involved in endocrine system of pancreas

A

islets of Langerhans involved in glucose homeostasis

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8
Q

what are islets of langerhans

A

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

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9
Q

why does insulin have a short half-life

A

there are proteases in the plasma

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10
Q

what is the structure of insulin

A

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

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11
Q

insulin biosynthesis

A
  • 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
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12
Q

how is insulin release regulated

A

glucose from food causes beta-cells to release insulin

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13
Q

how does low glucose levels cause low basal insulin secretion

A
  • glucose metabolised in cell
  • causes an increased ATP:ADP ratio
  • ATP-sensitive K channels are open
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14
Q

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

A
  • 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
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15
Q

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

A

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

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16
Q

what causes an increase in insulin release

A

glucagon released from alpha-cell

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17
Q

what inhibits insulin release

A

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

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18
Q

how does the parasympathetic nervous system muscarinic receptors affect beta cells

A

stimulates insulin release

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19
Q

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

A

inhibit insulin release

20
Q

how do beta-ARs affect beta cells

A

stimulate insulin release

21
Q

what receptors do beta cells express

A

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

22
Q

what does insulin promote

A
  • 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
23
Q

how does blood glucose affect the liver

A
  • increased glycogen synthesis
  • decreased glycogen breakdown
  • decreased gluconeogenesis (glucose production from intermediates)
24
Q

how does glucose affect the muscle

A
  • increased glucose uptake via GLUT-4 receptor
  • increased protein synthesis
  • decreased protein breakdown
25
Q

how does glucose affect adipose tissue

A
  • increased glucose uptake via GLUT-4
  • increased lipogenesis
  • decreased lipolysis
26
Q

how do tyrosine kinase receptors work when insulin attach

A
  • 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
27
Q

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

A

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

28
Q

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

A
  • Shc and gets phosphorylated
  • Grb2
  • SOS which leads to MAPK which causes cell survival and cell proliferation
29
Q

what is glucagon

A

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

30
Q

where is glucagon synthesised

A

islet alpha-cells

31
Q

when is glucagon released

A

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

32
Q

when is glucagon release inhibited

A

by high blood glucose, insulin and somatostatin (paracrine)

33
Q

what is the main action of glucagon

A

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

34
Q

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

A

decreased glucagon production and increased insulin production

35
Q

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

A

increased glucagon production and decreased insulin production

36
Q

what is somatostatin

A

a peptide hormone

37
Q

where is somatostatin synthesised

A

islet delta-cells and also in CNS and GIT

38
Q

what effects does somatostatin have

A

inhibits glucagon and insulin secretion by paracrine mechanism

39
Q

what is normal blood glucose range

A

4-8mmol/L

40
Q

what happens when glucose is raised

A

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

41
Q

what happens when glucose gets too low

A

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

42
Q

when is adrenaline used

A

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

43
Q

when is cortisol used

A

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

44
Q

when is growth hormone used

A

to promote growth
(if have prolonged hypoglycaemia)

45
Q

what disease is caused by chronic hyperglycaemia

A

diabetes mellitus

ENDOCRINE (17 decks)

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