insulin production, secretion and action

Question 1

where is the pancreas found

Answer 1

next to duodenum, under the liver

Question 2

what do beta, alpha and delta cells secrete respectively

Answer 2

insulin, glucagon, somatostatin

Question 3

what do PP cells secrete

Answer 3

pancreatic polypeptide

Question 4

how is insulin peptide made

Answer 4

synthesised in RER of pancreatic cells as larger prehormone, then cleaved to insulin

Question 5

how many polypeptide chains does insulin have and what are they linked by

Answer 5

2, disulphide bonds

Question 6

through what channel does glucose enter a beta cell

Answer 6

GLUT 2

Question 7

what happens do glucose immediately after it enters a beta cell

Answer 7

phosphorylated by glucokinase (glycolysis) which increases intracellular ATP

Question 8

after an intracellular increase of ATP in beta cells what happens

Answer 8

ATP inhibits ATP sensitive K channels and there is a build up of intracellular K leading to depolarisation

Question 9

once a beta cell is depolarised what happens

Answer 9

voltage gated calcium channels open and calcium enters the cell, increased intracellular calcium causes the release of glucose

Question 10

where does glucokinases maximum concentration of glucose lie (km)

Answer 10

physiological range of 5-7 mol/l

Question 11

what happens if there is too much glucose in the blood

Answer 11

glucokinase can’t phosphorylate it quickly enough so increased glucose remains in blood

Question 12

what type of receptors are insulin receptors

Answer 12

tyrosine kinases

Question 13

what happens when insulin binds to receptor

Answer 13

binds to alpha subunit, beta subunit phosphorylates which leads to cascade in the cell

Question 14

how is insulin released (phases)

Answer 14

biphasic

Question 15

what percent of insulin is immediately ready for release (RRP)

Answer 15

5%

Question 16

what happens in T2DM (phases)

Answer 16

insulin secretion weakens and only one phase

Question 17

what makes up the K/ATP channel

Answer 17

Kir6.1 proteins and SUR1 proteins

Question 18

what inhibits K/ATP and therefore causes depolarisation and insulin release (physiologically and pharmacologically)

Answer 18

ATP and sulphonylurea (SURs)

Question 19

what activates K/ATP and therefore inhibits insulin secretion

Answer 19

diazoxide

Question 20

what mutation can lead to neonatal diabetes

Answer 20

Kir6.2

Question 21

what type of hormone is insulin

Answer 21

anabolic

Question 22

what does insulin activate when it binds to receptor (biological effects) (5)

Answer 22

amino acid uptake in muscle, DNA/ protein synthesis, lipogenesis in adipose tissue, growth response (GH), glycogen synthesis

Question 23

what does insulin inhibit when it binds to receptor (biological effects) (2)

Answer 23

lipolysis and gluconeogensis

Question 24

what is leprechaunism/ syndrome

Answer 24

rare condition leading to severe insulin resistance

Question 25

what type of inheritance is leprechaunism/ syndrome and what mutation occurs

Answer 25

autosomal recessive, mutation in insulin receptor gene –> reduced binding/ signalling

Question 26

what are the symptoms of leprechaunism/ syndrome

Answer 26

elfin face, growth retardation, absence of subut fat, decreased muscle mass

Question 27

what type of inheritance is Rabson mendenhall syndrome and what mutation occurs

Answer 27

autosomal recessive, insulin receptor mutation

Question 28

what are the symptoms of Rabson mendenhall syndrome

Answer 28

severe insulin resistance, hyperglycaemia, compensatory hyperinsulinaemia, developmental abnormalities, acanthosis nigricans (hyperpigmentation)

Question 29

what happens in the absence of insulin (DKA)

Answer 29

no regulation of lipolysis leads to increased ketone bodies

Question 30

how are ketones formed

Answer 30

in mitochondria from beta oxidation of fats, acetyl CoA converted to ketones

Question 31

what are the symptoms of DKA

Answer 31

vomiting, dehydration, glucose in urine, increased HR, smell on breath

Question 32

what is diabetes

Answer 32

chronic, metabolic disease with high blood glucose that can affect various organs

Question 33

describe T1DM

Answer 33

absolute insulin deficiency, autoimmune disorder causing beta cell failure

Question 34

descrive T2DM

Answer 34

relative insulin deficiency causing hyperinsulinemia and resistance

Question 35

what does HbA1c measure and what are normal values

Answer 35

glycated haemoglobin, >41 = risk, >48 = diabetes

Question 36

what values are used for fasting and random glucose

Answer 36

fasting: <6 moll normal, >7 moll

random glucose >11.1

Question 37

apart from T1/2DM what types of diabetes are there

Answer 37

gestational, MODY, endocrine disorders (type 4), monogenic