insulin

Question 1

structure of insulin

Answer 1

C-term A chain linked via disulphide bonds to N-term B chain

C-peptide cleaved

Question 2

implication of C-peptide levels

Answer 2

arise only from endogenous insulin, indicates endo synthesis of insulin

Question 3

what stimulates insulin release

Answer 3

glucose, amino acids, parasympathetic release of ACh

increase intracellular Ca2+ in b-cells –> insulin release

Question 4

what suppresses insulin release

Answer 4

adrenaline

Question 5

properties of GLUT2

Answer 5

high Km, low affinity
expressed in liver and pancreatic b-cells

constitutively expressed in b-cells

liver – uptake of excess glucose
b-cell – regulation of insulin

Question 6

properties of GLUT 1,3

Answer 6

basal glucose uptake

all mammalian tissues

Question 7

properties of GLUT4

Answer 7

main uptake of glucose

primarily in muscle and fat cells

Question 8

actions of insulin

Answer 8

• facilitate glucose uptake
• decrease rate of lipid and protein breakdown
• increase glycolysis
• decrease glycogen breakdown
• increase glycogen synthesis
• promote cell division and growth

Question 9

termination of insulin action

Answer 9

internalisation and metab by lysosomes of insulin-receptor complex

receptors recycled to membrane

Question 10

insulin clearance

Answer 10

first-pass in liver: removes ~50% of endo insulin

kidney: 50% insulin clearance from systemic circulation (main clearance for exo insulin)

Question 11

indications for insulin therapy

Answer 11

type I: must take insulin (deficiency)

type II: severe hyperglycaemia, glycemic target cannot be reached w 2/more oral hypoglycaemic agents

Question 12

types of insulin needed

Answer 12

basal: suppress hepatic glucose pdtn overnight and b/w meals

prandial: to dispose of glucose after eating

Question 13

types of insulin therapy

Answer 13

all administered via subcutaneous injection, diff rates of absorption

• rapid acting
• short acting
• intermediate acting
• long acting (cannot be mixed)
• premixed

Question 14

rapid acting insulin

Answer 14

insulin lispro, aspart, glulisine

modification of aa –> changes to charge/conformation of insulin at physiological pH
(weaken propensity to self-associate through charge repulsion – rapid absorption of monomers)

injected j before meals, dose can be adjusted prop to amt of food

shorter duration of action –> lower incidence of hypoglycaemia

Question 15

short acting insulin

Answer 15

structurally similar to endo human insulin

self aggregates in subcutaneous tissue –> delayed onset by 30-60mins (inject 30 min before meal)

IV – immediate

greater risk of hypoglycaemia than rapid acting

Question 16

intermediate acting

Answer 16

neutral protamine hagedorn (NPH) insulin – recombinant human insulin + protamine

cloudy appearance (vs other types: clear)
relatively cheaper

precipitate crystals that slowly release – longer duration of action

delayed onset: 3-4h

greater risk of hypoglycaemia: high variability in NPH action, long peak effect – must eat as insulin level peaks

taken twice a day (effect: ~12h)

Question 17

long acting insulin

Answer 17

insulin glargine, detemir

virtually no plasma peak, act as basal insulin

cannot be mixed w other insulin

glargine: formulated at pH4, aggregates and slowly release at pH 7.4

detemir: c14 fatty acid side chain – increase self-association, reversible binding to albumin –> prolong action

more predictable fasting blood glucose, lower variation than NPH –> reduce risk of hypog

Question 18

what insulin cannot be mixed

Answer 18

glargine/detemir + other insulin
glulisine + non-NPH insulin

Question 19

routes of administration for insulin

Answer 19

subcutaneous – default
IV – emergency, immediate
nasal – rapid, highly vascularised lungs

avoid IM
avoid: bruises, scar tissue, near joints, groin, navel (belly button)

Question 20

adverse effects of insulin

Answer 20

hypoglycaemia

lipohypertrophy – lipogenic nature of insulin, rotate site of injection to reduce incidence

lipodystrophy (more relevant when animal insulin used)

Question 21

factors affecting PK of insulin

Answer 21

• site of injection – blood flow
• depth of injection – superficial: slower, deeper: faster
• larger vol delay absorption
• exercise muscle – increase rate of absorption
• massage site/heat: increase rate of absorption

Question 22

effect of steroid on blood glucose

Answer 22

steriod: drug induced hyperg

monitor blood glucose closely, may need to increase insulin