insulin Flashcards
(22 cards)
structure of insulin
C-term A chain linked via disulphide bonds to N-term B chain
C-peptide cleaved
implication of C-peptide levels
arise only from endogenous insulin, indicates endo synthesis of insulin
what stimulates insulin release
glucose, amino acids, parasympathetic release of ACh
increase intracellular Ca2+ in b-cells –> insulin release
what suppresses insulin release
adrenaline
properties of GLUT2
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
properties of GLUT 1,3
basal glucose uptake
all mammalian tissues
properties of GLUT4
main uptake of glucose
primarily in muscle and fat cells
actions of insulin
- facilitate glucose uptake
- decrease rate of lipid and protein breakdown
- increase glycolysis
- decrease glycogen breakdown
- increase glycogen synthesis
- promote cell division and growth
termination of insulin action
internalisation and metab by lysosomes of insulin-receptor complex
receptors recycled to membrane
insulin clearance
first-pass in liver: removes ~50% of endo insulin
kidney: 50% insulin clearance from systemic circulation (main clearance for exo insulin)
indications for insulin therapy
type I: must take insulin (deficiency)
type II: severe hyperglycaemia, glycemic target cannot be reached w 2/more oral hypoglycaemic agents
types of insulin needed
basal: suppress hepatic glucose pdtn overnight and b/w meals
prandial: to dispose of glucose after eating
types of insulin therapy
all administered via subcutaneous injection, diff rates of absorption
- rapid acting
- short acting
- intermediate acting
- long acting (cannot be mixed)
- premixed
rapid acting insulin
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
short acting insulin
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
intermediate acting
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)
long acting insulin
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
what insulin cannot be mixed
glargine/detemir + other insulin
glulisine + non-NPH insulin
routes of administration for insulin
subcutaneous – default
IV – emergency, immediate
nasal – rapid, highly vascularised lungs
avoid IM
avoid: bruises, scar tissue, near joints, groin, navel (belly button)
adverse effects of insulin
hypoglycaemia
lipohypertrophy – lipogenic nature of insulin, rotate site of injection to reduce incidence
lipodystrophy (more relevant when animal insulin used)
factors affecting PK of insulin
- 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
effect of steroid on blood glucose
steriod: drug induced hyperg
monitor blood glucose closely, may need to increase insulin
