Diabetes Flashcards
What is the structure of active insulin
consists of 2 peptide chain connected by disulphide bond
How does proinsulin become insulin
enzyme cleave off C peptide to release active insulin, and C peptide arises only from endogenous insulin
Where is insulin stored
in pancreatic B cells packed into densely clustered granules consisting of insoluble crystalline hexameric insulin
What stimulates insulin release, and how does it work
glucose, amino acid like arginine, leucine and parasympathetic release of ACH.
acts via phospholipase C-lP3 pathway to increase intracellular Ca2+ in pancreatic beta cell
What supresses insulin release
adrenaline
how does the insulin receptor look like
2 heterodimers each containing an extracelular a subunit and transmembrane B subunit, containing tyrosine kinase
What is Glut 2 Km
15-20mM. considered high Km, low substrate affinity
what is the function of insulin
maintain normal blood glucose through
- facilitating cellular glucose uptake, regulate carb, lipid and protein metabolism, promote cell division and growth
Where is insulin cleared
major site is the kidney, removes about 50% of peripheral insulin via glomerular filtration and proximal tubular reabsorption and degradation
What causes type 1 diabetes
immune mediated B cell destuction leading to absolute insulin deficiency
What level of insulin does insulin therapy need to achieve
basal insulin level and prandial insulin level
In what situation do type 2 diabetes also need insulin therapy
when they have sever hyperglycemia, or glycemic targets were not reached with 2 or more oral hypogycemic agents. Insulin can be given alone or in combination with OHA
What are the types of insulin analogues
rapid acting insulin analogues: insulin lispro, insulin aspart, insulin glulisin
short acting insulin: regular human insulin
intermediate acting insulin: neutral protamine hagedorn
long acting insulin: insulin glargine and insulin detemir
What is good about rapid acting insulin anlogue
- they demonstrate faster absorption kinetics, can be injected just before meals
- they attain higher concentration after subcutaneous injection compared to conventional human insulin and reduce post prandial glucose to a greater extenet
- they have shorter duration of action, can lead to lower incidence of hypoglycemia
- dose can be adjusted proportionate to fod consumed
What are short acting insulin consisted of
dissolved zinc-insulin crystals
Why is there a delayed onset of action of 30-60 mins for short acting insulin
because they aggregate in subcutaneous tissue
What determines the hypoglycemic risk of insulin therapy
the duration of action, the longer the more risk
What is Neutral Protamine Hagedorn comprised of
combination of human insulin with protamine
what is the dosing regime for Neutral Protamine Hagedorn
typically twice a day
What is the potential adverse effect of using NPH
High risk of hypoglycemia, due to high intra and inter patient variability of NPH action and
Long peak effect. NPH insulin acts as a basal and prandial insulin, necessitating that patients eat a meal at the time the insulin is peaking
at what pH is insulin glargine formulated?? At what Ph will it be activate
formulated at ph4. At ph7 is when it forms aggregate that slowly release insulin over time
What should glargine not be mixed with
any other insulins
What is the only insulin that can be mixed with glulisin
NPH
Where should you not administer insulin and why
intramuscularly, beacause hard to predict onset and duration of action and the peak of action
What are the factors affecting the pharmacokinetics of insulin
- site of injection, abdomen faster and more reproducible absorption due to difference in blood flow
- depth of injection, make sure it is into subcutaneous tissue.
- larger volume can delay absorption
- exercising the muscle group before injecting insulin into the area can increase absorption of insulin
5.massage of injection area
What are some adverse effect of insulin therapy
- hypoglycemia
2.lipodystrophy
- lipohypertrophy
what are some symptoms of hypoglycemia
dizziness, tremor, confusion weakness
What are ways to regulate blood glucose level
- insulin sensitisers
- a- glucosidase inhibitor
- Insulin secretagogues
- incretin based therapy
- SGLT-2 inhibitors
what is an example of an insulin sensitiser
metformin( a biguanide), thiazoldinediones like pioglitazone and rosiglitazone