Therapeutic drug overview of the two types of diabetes mellitus
Type I insulin with thiazolidinedione for severe insulin resistance Type II metformin other oral hypoglycemic agent α-glucuronidase inhibitor combination of metformin and thiazolidinedione or sulfonylurea insulin ACEI to reduce HTN (nephroprotective)
What is the clinical use of glucagon?
catabolism of glycogen stores into glucose
use for severe hypoglycemia and treat or prevent diabetic coma
diagnosis of DM I
beta blocker poisoning (to reverse B1 blockade)
What kind of receptor is the insulin receptor?
tyrosine kinase receptor upon ligand binding, forms dimers and phosphorylates each other
activates phosphoinositol-3-kinase which activates PKC and Akt responsible for glucose transport, glycogen synthesis, lipid synthesis, protein synthesis
What are the target tissues of insulin?
skeletal and cardiac muscles, liver, adipose
stimulates anabolic processes for controlling uptake, use and storage of glucose, amino acids, and fatty acids
inhibits catabolic processes in breakdown of glycogen, protein, and fats
What chemicals and neuronal stimulation promotes insulin secretion?
glucose, amino acids, ketones
parasympathetic stimulation (vagal)
hormones associated with digestion (gastric inhibitory peptide)
What inhibits insulin secretion?
How does high glucose activate insulin release?
glucose enters β-cell (GLUT2) → G6P (glucokinase) TCA cycle increases ATP ↑ ATP/ADP ratio inhibits KIR6.2 (K+ inward rectifier channel) partial depolarization of cell opens voltage gated Ca2+ channels ↑ Ca2+ causes release of insulin from docked vesicles
Since 2003, how are insulin replacement preparations synthesized?
all insulin made by varying recombinant DNA techniques of human origin stabilized around zinc ions (Novolin R, Humulin R, Velosulin R)
insulin delivered via subcutaneous injections via insulin pumps
inhalation devices under development
What is the physiological state of insulin in the body? (i.e. how normal endogenous insulin exists)
insulin stored as dimers that naturally form hexamers
physiologically active insulin is in monomer form
How does the polymerization of insulin affect its absorption rate?
three rates of absorption based on aggregation state of insulin
hexamers - slowest rate
dimers - intermediate rate
monomers - fastest rate
to replace basal and post-prandial insulin levels
using combination of
rapid acting, rapid onset (short duration) drugs and
intermediate and long acting drugs
When should sort acting (human recombinant) insulin products be administered?
30 to 40 mins before meal effective peak action in 2 to 3 hours duration of action 5 to 8 hours
slower absorption rate than rapid acting short duration modified insulin drugs (lispro, aspart, glulisine)
prevents early post-prandial hyperglycemia
What are 2 long acting drugs that replace basal insulin levels?