Insulin

Question 1

what kind of hormone is insulin

Answer 1

peptide hormone

Question 2

why is insulin used as a murder weapon

Answer 2

causes hypoglycaemic coma and death

very difficult to prove as cause of death

Question 3

what cell makes insulin

Answer 3

beta cell in the pancreas - only cells that can make insulin - sense blood glucose

Question 4

what cells make glucagon

Answer 4

alpha cells

Question 5

what cells make somatostatin

Answer 5

delta cells

Question 6

what does somatostatin do

Answer 6

controls the release of glucagon and insulin

Question 7

what do PP cells secrete

Answer 7

pancreatic polypeptide

Question 8

where is insulin synthesised

Answer 8

in the rough endoplasmic reticulum of pancreatic B cells as larger chain peptide - cleaved to form insulin

Question 9

what is the chemical structure of insulin

Answer 9

two polypeptide chains linked by disulfide bones

connecting C peptide has no use - bi product of cleaving

Question 10

how do you make lispro insulin

Answer 10

swap two amino acids - PRO and LYS

Question 11

characteristics of lispro

Answer 11

short acting- ultra fast
injected within 15 mins of beginning meal

compbination with longer acting preparation for type 1 diabetes

Question 12

how to make insulin glargine

Answer 12

swap GLY for ARG ARG amino acids

Question 13

characteristics of glargine

Answer 13

ultra long acting

given as single bedtime dose

Question 14

how does glucose enter B cells

Answer 14

via GLUT2 transporter

Question 15

what enzyme phosphorylises glucose in B cells

Answer 15

glucokinase

Question 16

why is glucokinase used to sense glucose levels

Answer 16

small change in glucose conc causes a dramatic change in glucokinase activity

Question 17

what causes depolarisation of the B cell membrane

Answer 17

ATP inhibiting the K+ channel

Question 18

what causes the opening of Ca++ channels in the B cells

Answer 18

depolarisation of the cell

Question 19

what happens then the level of Ca++ in the cell increases

Answer 19

fusion of secretory vesicles with the cell membrane and release of insulin

Question 20

what level of blood glucose triggers insulin release

Answer 20

5mM

Question 21

those with T1DM have B cells true/false

Answer 21

true but they’re mostly lost

Question 22

those with T2DM have B cells true/false

Answer 22

true

they’re just not sensitive anymore due to hyperglycaemia taking glucose conc outwit the km of glucokinase

Question 23

what are there two waves of insulin release

Answer 23

a reserve pool of secondary preparations is there and available for release in case the first one isnt enough

Question 24

pharmacological treatment options for T2DM

Answer 24

restoring physiological glucose to enhance insulin secretion

pharmacological regulation os the secretion process - drugs mimic ATP to depolarise B cells

Question 25

what class of drugs target the Katp channel

Answer 25

sulphonylurea drugs (SURs) allow depolarisation of B cells stimulating insulin release

Question 26

what stimulates Katp channels to inhibit insulin secretion

Answer 26

diazoxide

Question 27

why are SURs only second line in T2DM

Answer 27

the B cells are already working v hard and are v stressed so making the work harder can be counter intuitive

Question 28

what mutations can lead to neonatal diabetes

Answer 28

Kir6.2 give contritiutively activated Katp channels

Question 29

what is maturity-onset diabetes of the young

Answer 29

monogenic diabetes with genetic defect in B cell function famillial form of early onset T2DM mutations in at least 6 different genes can cause this

Question 30

what happens to glucokinase in maturity-onset diabetes of the young

Answer 30

glucokinase activity impaired | glucose secreting defect - blood glucose threshold for insulin increased

Question 31

what is type 1 diabetes

Answer 31

loss of insulin secreting B cells

Question 32

what is MODY

Answer 32

maturity onset diabetes of the young defective glucose sensing in the pancreas and/or loss of insulin secretion

Question 33

what is t2dm

Answer 33

initial hyperglycaemia with hyperinsulinemia so primary problem is desensitisation of B cells

Question 34

what happens when insulin is being released (anabolic hormone)

Answer 34

``` amino acid uptake in muscle DNA synthesis protein synthesis growth responses glucose uptake in muscle and adipose tissu e lipogenesis in adipose tissue and liver glycogen syntehsis ```

Question 35

what happens when insulin binds to an insulin receptor

Answer 35

receptor tyrosine kinase activity - autophosphylates leading to binding of proteins to the receptor starting a cascade

Question 36

what are the 2 major pathways insulin uses for its dozen of pathways

Answer 36

PI3K (PI3 kinase) | Ras

Question 37

what causes insulin resistance

Answer 37

reduces insulin sensing and/or signalling | causes by obesity or near complete absence of adipose tissue

Question 38

best treatment for obesity linked T2DM

Answer 38

WEIGHT LOSS

Question 39

what is leprechaunism

Answer 39

rare autosomal recessive genetic treat mutations in the gene for the insulin receptor causing severe insulin resistance developmental abnormalities - absence of subcutaneous fat, decreases muscle mass, growth retardation

Question 40

what is rabson Mendenhall syndrome

Answer 40

rare autosomal recessive genetic trait severe insulin resistance, hyperglycaemia and hyperinsulinemia diabetic ketoacidosis linked to mutations in insulin receptor

Question 41

symptoms of diabetic ketoacidosis

Answer 41

vomiting dehydration increased heart rate distinctive smell on breath

Question 42

where are ketone bodies formed

Answer 42

in the liver in the mitochondria

Question 43

what do Ketone bodies do

Answer 43

molecules of energy metabolism for heart muscle and renal cortex

Question 44

how do low levels of insulin prevent ketone body overload

Answer 44

by inhibiting lipolysis

Question 45

consequences of accumulation of ketone bodies

Answer 45

coma and death

Question 46

when are ketone bodies formed

Answer 46

when glucose is not available fatty acids are oxidised to provide energy this doesn't need acetyl co-A involvement excess acetyl co-A is converted to ketone bodies