1 - biochemistry of glucose & insulin

Question 1

briefly describe glucose homeostasis?

Answer 1

fasting = glucose levels drop (below 5mM) the alpha cells release glucagon to increase glucose & prevent hypoglycaemia

eat = glucose levels raise (above 5mM) the beta cells release insulin to decrease glucose & prevent hyperglycaemia

Question 2

what happens if glucose below 3mM?

Answer 2

brain shuts down and experience confusion and delirium and coma = severe hypoglycemia

Question 3

what is hypoglycemia?

Answer 3

below 4mM glucose (risk of coma)

Question 4

what is healthy blood glucose level?

Answer 4

4-6mM

Question 5

what is pre diabetes?

Answer 5

when have blood sugar 6-7mM and thought to have high risk of diabetes

Question 6

what is hyperglycaemia?

Answer 6

above 7mM = too high blood glucose

Question 7

what is meant by insulin has very small physiological window? (why does it mean risk drug?)

Answer 7

it means that if you take too much it kills you by hypoglycaemic coma. its very fast to act

Question 8

what is secreted by the 4 cells in islets of langerhans?

Answer 8

beta cells = insulin
alpha cells = glucagon
delta cells = somatostatin
PP cells = pancreatic polypeptide

Question 9

what is C-peptide?

Answer 9

by product of cleavage of insulin (from preproinsulin cleaved to insulin)
= it can be measured to see if pancreas working

Question 10

what are the different forms of insulin that act at different speeds?

Answer 10

lispro = ultra fast (injected within 15 min of beginning meal)
regular = fast acting
NPH = intermediate acting
ultralente = long acting
glargine = ultra long acting (slow release, single dose at bedtime)

Question 11

describe the process of insulin release in pancreatic beta cells?

Answer 11

• glucose enters beta cells through GLUT2 and is phosphorylated by glucokinase (then enters glycolysis)
• glucose comes in cell and helps cell make lots of ATP →glucokinase controls
• ATP binds to ATP sensitive K+ channel and inhibits →depolarisation of cell membrane which regulates calcium channels →influx Ca2+ →increase in Ca2+ means fusion of secretory vesicles with cell membrane & release of insulin

Question 12

what is meant by biphasic secretion of insulin?

Answer 12

beta cell releases insulin in 2 phases = thought to be because you have some insulin granules sitting and ready to go (readily releasable pool) so released immediately and then you’ve got some that needs to be still made so that’s 2nd phase (reserve pool)

Question 13

what are 5 types of diabetes?

Answer 13

• type 1 diabetes mellitus
• type 2 diabetes mellitus
• gestational diabetes
• maturity onset diabetes of young
• neonatal diabetes

Question 14

what is type 1 diabetes? what is definitive diagnosis?

Answer 14

= autoimmune destruction of pancreatic beta cells

definitive diagnosis = presence of autoantibodies combined with declining c-peptide production

Question 15

what is type 2 diabetes?

Answer 15

= presents hyperinsulinemia (in attempt to compensate insulin resistance - not completely resistant)

almost always end up with insulin injection treatment

Question 16

what is gestational diabetes?

Answer 16

when during pregnancy, hyperglycaemia detected (5.5mM in pregnant women). mostly identifies women with declining beta cell function, often 1st step of type 2 diabetes (much higher risk of developing type 2) - complications is large baby & serious birth problems. manage lifestyle advice and sometimes metformin to improve insulin sensitivity. = common. after birth no longer diabetic

Question 17

what is maturity onset diabetes of young?

Answer 17

beta cell dysfunction disease (but not autoimmune). rare. monogenic. treat with sulphonylurea

Question 18

what is neonatal diabetes?

Answer 18

caused by mutations in glucose sensing mechanism, rare, monogenetic

Question 19

what are 2 proteins required for function for K+ channels?

Answer 19

1. inward rectifier subunit - pore subunit = Kir6
2. sulphonylurea receptor- regulatory subunit - SUR1
   = they can have mutations in neonatal or MODY diabetes

Question 20

what directly inhibits and directly stimulates KATP channel?

Answer 20

inhibits = sulphonylurea
stimulated = diazoxide

*forces channel closed so no insulin made

Question 21

what receptor family is insulin a member of?

Answer 21

tyrosine kinase receptor family = conformational cascade of receptor causing cascade

Question 22

what are 2 genetic diseases of severe insulin resistance?

Answer 22

1. leprechaunism - donohue syndrome
2. rabson mendenhall syndrome

Question 23

what is donohue syndrome?

Answer 23

• rare autosomal recessive genetic trait
• mutations in gene for insulin receptor = sever insulin resistance
• would first present with developmental abnormalities. caused by defects in insulin binding or signalling

Question 24

what is robson mendenhall syndrome?

Answer 24

• a rare autosomal recessive
• sever insulin resistant, hyperglycemia, compressor hyperinsulinemia
• developmental abnormalities
• acanthosis nigricans (hyperpigmentation)
• fasting hypoglycemia (due to hyperinsulinemia)
• diabetic ketoacidosis
• severe cases linked to mutations in insulin receptor that reduce sensitivity

Question 25

what are symptoms of diabetic ketoacidosis?

Answer 25

vomiting, dehydration, increased heart rate, sickly sweet smell on breath

Question 26

what is process causing ketoacidosis?

Answer 26

ketones are important molecules for energy. having no insulin means body switches from glycolysis and citric acid cycle to fatty acid oxidation which uses ketone bodies as energy