Insulin Therapy

Question 1

Precursor to insulin

Answer 1

proinsulin - a chain + b chain bonded by 2 disulfide bonds

Question 2

cpeptide

Answer 2

portion of proinsulin that is cleaved in formation of insulin –> clinical marker of endogenous insulin production

Question 3

insulin production

Answer 3

proinsulin packaged in golgi –> proteolytic cleave to insulin + c peptide –> zn added forming hexameric crystalline insulin –> stored in granules

Question 4

Insulin binds to _____ receptors with strong affinity and specificity.

Answer 4

insulin and igf1 –>tyrosine kinase and protein phsphorylation cascade

Question 5

endogenous insulin metabolism

Answer 5

B cell –> bloodstream –> portal vein –> liver (60% degrade via first pass, 40% in kidneys)

Question 6

exogenous insulin metabolism

Answer 6

subcutaneous tissue –> bloodstream –> kidney (60%) –> liver (40%)

Question 7

Insulin promotes/inhibits triglyceride synthesis and storage

Answer 7

promotes

Question 8

Insulin promotes/inhibits lipolysis

Answer 8

inhibits

Question 9

Insulin promotes/inhibits glycogen synthesis in muscle

Answer 9

promotes

Question 10

Insulin promotes/inhibits aa uptake in muscle

Answer 10

promotes

Question 11

Insulin promotes/inhibits protein synthesis in muscle

Answer 11

promotes

Question 12

Insulin promotes/inhibits glycogen synthesis in liver

Answer 12

promotes

Question 13

Insulin promotes/inhibits fa synthesis in liver

Answer 13

promotes

Question 14

Insulin promotes/inhibits glucose output in liver

Answer 14

inhibits

Question 15

Insulin promotes/inhibits ketogenesis in liver

Answer 15

inhibits

Question 16

T/F human synthetic insulin is packaged at neutral pH

Answer 16

F –> all except glargine

Question 17

Rapid-acting human analogs/bolus are used for

Answer 17

coverage of food intake and correction of hyperglycemia
short acting = regular
rapid acting = aspart, lispro, glulisine

Question 18

short-acting regular insulin are used for

Answer 18

mealtime hyperglycemia

Question 19

long-acting insulins/basal

Answer 19

maintain euglycemia in the fasting state (NPH = 2x per day, long acting = glargine, detemir)

Question 20

Aspart and lispro are ___ with regular human insulin

Answer 20

homologous –> single exchanges in each –> disrupt monomer-monomer interactions = less hexamer formation = more rapid absorption after subq injection

Question 21

Compare glucose lowering effects of aspart/lispro vs. normal insulin

Answer 21

similar (affinity, induction, bioavailability)

Question 22

Compare pharmacokinetics of aspart/lispro vs. normal insulin

Answer 22

aspart/lispro 2x faster, 2x higher peak concentration, faster onset of action, shorter duration of action

Question 23

NPH

Answer 23

neutral protamine hagedorn/humulin/novolin/isophane –> suspension of crystalline zinc insulin with positively charged polypeptide proamine

Question 24

Glargine

Answer 24

long-acting insulin analogue with a few changes that create an acidic pH –> precipitates in subcutaneous tissue –> slow breakdown

Question 25

Detemir

Answer 25

soluble long acting basal insulin analog –> binds to albumin and dissolves slowly

Question 26

Which of NPH/glargine/detemir is intermediate duration?

Answer 26

nph

Question 27

Insulin administration modes

Answer 27

subq and IV

Question 28

IV insulin indications

Answer 28

hospitalized patients and acute management of metabolic crises –> rapid onset/decay

Question 29

Complications of insulin delivery

Answer 29

hypoglycemia, inuslin lipatrophy/hyerptrophy at injection sites, allergy, resistance