Biochemistry

Question 1

what is the pancreas made up of?

Answer 1

islets of Langerhans

Question 2

islets of Langerhans types

Answer 2

alpha (glucagon)
beta (insulin)
delta (somatostatin)
PP cells (polypeptide)

Question 3

formation of insulin

Answer 3

• synthesised in the RER of beta cells as a single chain preprohormone (preproinsulin)
• cleaved to form insulin which contains two polypeptide chains linked by disulphide bonds
• connecting C-peptide is a byproduct of cleavage

Question 4

two insulin preparations

Answer 4

1. ultrafast/short-acting e.g. insulin lispro

2. ultra-long acting e.g. insulin glargine

Question 5

describe the structure of ultrafast insulin

Answer 5

insulin lisper (lysine [B28] and proline [B29] is monomeric, injected within 15 minutes of beginning a meal, short duration of action and combined with longer preparations in T1DM.

Question 6

describe the structure of insulin glargine

Answer 6

this is a recombinant insulin analogues that precipitates in a neutral environment of subcutaneous tissue. single bedtime dose

Question 7

secretion of insulin

Answer 7

• glucose enters beta cels through GLUT2 and is phosphorylated by glucokinase (change in glucose concentration leads to a change in glucokinase activity)
• increased metabolism of glucose increases ATP production form glycolysis, TCA and OP
• inhibition of ATP-sensitive K+ channels and depolarisation of membrane
• opening of Ca2+ channels which causes fusion of secretory vesicles to release insulin

Question 8

at what blood concentration should beta cells release insulin

Answer 8

rising above 5nM

Question 9

describe the biphasic release of insulin

Answer 9

only 5% of insulin granules are immediately available for release (RRP). the reserve pool sun undergo preparatory reactions

Question 10

two proteins in the KATP channel

Answer 10

1. inward rectifier subunit (KIR)- pore subunit Kir6

2. sulfonylurea receptor- regulatory subunit SUR1

Question 11

what inhibits the KATP channel

Answer 11

SUs

diazoxide

Question 12

insulin actions as an anabolic hormone

Answer 12

• amino acid and glucose uptake in muscle, DNA and protein synthesis
• growth responses
• lipogenesis in adipose tissue and liver
• glycogenesis in liver and muscle
• switches off lipolysis and gluconeogenesis

Question 13

what does insulin bind to?

Answer 13

receptor tyrosine kinase alpha subunit causes the beta subunit to dimerise and autophosphoyrlation activating the receptor. two insulin pathways are PI3K and Ras

Question 14

what is a key mediator in insulin sensitivity

Answer 14

adipose tissue

Question 15

mutations in what cause monogenic insulin resistance?

Answer 15

AKT2

Question 16

leprechaunish- Donohue syndrome

Answer 16

AR mutation in gene for insulin receptor. there is severe insulin resistance and development abnormalities

Question 17

Rabson Mendenhall syndrome

Answer 17

AR mutation of insulin receptor that reduces sensitivity. severe insulin resistance, hyperglycaemia and hyperinsulinemia. presents with development abnormalities and acanthuses nigricans. fasting hypoglycaemia can lead to DKA

Question 18

DKA presentation

Answer 18

vomiting
dehydration
increased HR
ketones on breath

Question 19

formation of ketone bodies

Answer 19

formed in liver mitochondria derived from acetyl-CoA from beta-oxidation of fats. diffuse into bloodstream and peripheral tissues.

Question 20

how does insulin prevent ketosis?

Answer 20

inhibits lipolysis and prevents ketone body overload

Question 21

what limited substance can cause ketones?

Answer 21

pyruvate/oxaloacetate

Question 22

problems of no insulin

Answer 22

reduces the amount of glucose taken up by tissues from the blood, so fatty acids are oxidised for energy

Question 23

what does accumulation of ketone bodies cause?

Answer 23

acidosis, high glucose secretion causes dehydration, exacerbating acidosis

Question 24

management of DKA

Answer 24

insulin and rehydration