Insulin Preps MT2 Flashcards
this is a group of metabolic diseases characterized by high blood sugar (glucose) levels, which result from defects in insulin secretion, action or both
diabetes
how are glucose utilization, glucose production and insulin secretion affected in DM
glucose utilization: decreased
glucose production: increased
insulin secretion: decreased
normally, blood glucose levels are tightly controlled by _______ which is a hormone produced by the pancreas
insulin
what are the three main symptoms of diabetes
polydipsia - excessive thirst
polyphagia - increased appetite
polyuria - excessive passing of urine
type I or type II DM?
onset occurs usually < 20 y/o
type I
type I or type II DM?
obesity is usually present
type II
type I or type II DM?
onset occurs usually > 30 y/o
type II
type I or type II DM?
normal or increased blood insulin
type II
type I or type II DM?
decreased blood insulin
type I
type I or type II DM?
anti-islet cell antibodies are present
type I
type I or type II DM?
ketoacidosis is common
type I
type I or type II DM?
50% concordance in twins
type I
type I or type II DM?
60-80% concordance in twins
type II
type I or type II DM?
no HLA association
type II
type I or type II DM?
HLA-D linked
type I
type I or type II DM?
severe insulin deficiency
type I
type I or type II DM?
insulin resistance is present
type II
type I or type II DM?
autoimmune, immunopathologic mechanisms present
type I
type I or type II DM?
no insulitis present
type II
type I or type II DM?
marked atrophy and fibrosis
type I
type I or type II DM?
focal atrophy and amyloid deposits (amyloid gets secreted alongside insulin and if have this type of DM the amyloid gets deposited)
type II
type I or type II DM?
severe beta-cell depletion
type I
type I or type II DM?
mild beta-cell depletion
type II
what are some of the organs/systems that complications may occur in DM
- cardiovascular
- eyes
- kidneys
- nervous systems
- pancreas
what is used to diagnose diabetes
- fasting plasma glucose (above 7 mol/L)
- plasma glucose (above 11.1 mol/L)
- hemoglobin A1c (above 6.5%)
- symptoms of DM
true or false: type 1 DM is reversible
false
true or false: type 2 DM is reversible
true
true or false: gestational DM is reversible
true
blood glucose levels tend to be higher in untreated ____1____ than untreated ___2____ because _____3____ subjects retain some insulin action
1 - type 1
2 - type 2
3 - type 2
this is stored in the liver in the form of glycogen
glucose
its effect is to lower blood glucose levels. it is activated during the fed state, where blood glucose levels are high. low levels release adipocytes from inhibition
insulin
this peptide increases glucose levels. hepatocytes have receptors for this peptide which convert the glycogen polymer to individual glucose molecules to be released into the blood. when glucose stores are depleted, this peptide induces glycogenolysis by the liver and kidney
glucagon
this is stored within granules in the beta-cells of the pancreas. the half life is 3-5 mins
endogenous insulin
two organs are responsible for removing insulin from circulation. these organs are
- liver
- kidney
free insulin binds to insulin receptors primarily on what organs
liver, muscle and adipose tissue
what type of receptors are insulin receptors?
tyrosine kinase
- alpha subunit is the binding domain
- beta subunit is the ATP-binding and tyrosine kinase domains
only ___% of insulin receptors need to be occupied to produce the maximum effect
10
when the activated insulin receptor phosphorylates, it becomes an insulin receptor substrate. rapid effects are mediated by this pathway
PI3K
when the activated insulin receptor phosphorylates, it becomes an insulin receptor substrate. long term effects are mediated by this pathway
MAP kinase
this GLUT transporter is found in all tissues, especially red cells and the brain.
function: basal glucose uptake & transport across the BBB
GLUT1
this GLUT transporter is found in the beta-cells of the pancreas; liver, kidney and gut.
function: regulation of insulin release & glucose homeostasis
GLUT2
this GLUT transporter is found in the brain, kidney, placenta and other tissues
function: uptake into neurone and other tissues
GLUT3
this GLUT transporter is found in the muscle and adipose tissue.
function: insulin-mediated uptake of glucose
GLUT4
this GLUT transporter is found in the gut and kidney
function: absorption of fructose
GLUT5
what are the different ways insulin preparations differ by?
- source (human or animal species from which they are derived)
- purity
- concentration
- solubility
- time of onset and duration of action
these insulin preparations are dispensed as clear solutions at a neutral pH. they also have small amounts of zinc to increase shelf-life.
ultra short acting and short acting insulins
these insulin preparations are cloudy and have been modified in some way to permit slower onset and longer duration.
intermediate and long acting insulins
what are some adverse effects of insulin
- hypoglycaemia
- loss of fatty tissue at site of injections (rotate!)
- insulin allergy (rare)
- insulin resistance (very rare)
examples include Insulin Lispro, Insulin Aspart and Insulin Glulisine
rapid acting human insulin analogs
examples include regular insulin
short acting insulin
examples include NPH insulin
intermediate acting insulin
examples include insulin glargine and insulin detemir
long acting human insulin analogs
what is the onset of action, peak and effective duration of very rapid acting insulin (e.g. Aspart, Glulisine and Lispro)
onset: <0.25, peak is 0.5-1.5 hr and may last for 3-4 hrs
what is the onset of action, peak and effective duration of short acting (regular) insulin
onset 0.5-1 hr, peak is 2-3 hrs and may last for 4-6 hrs
what is the onset of action, peak and effective duration of long acting insulin (e.g. detemir, glargine, degludec and NPH - intermediate)
onset: 1-4 hrs, peak = relatively constant and may last for 10-42 hrs, depending on specific insulin
what is the onset of action, peak and effective duration of combination insulins (long acting and short acting)
onset: 0.25-1hr, peak is 1.5 hr and may last for 10-16 hrs
what is the FIRST LINE treatment of type II DM
lifestyle changes such as diet, weigh loss, exercise, education.
what pharmaceutical agents may be used to treat type II DM
oral hypoglycemics such as sulphonylureas, biguanides, thiazolidinediones, meglitinides and alpha-glucosidase inhibitors (sometimes insulin)
this type of oral hypoglycemic are derived from sulfonic acid and urea. examples include gliclizide, tolbutamide, glyburide, etc.
sulphonylureas and secretagogues
what are some side effects of sulphonylureas and secretagogues
hypoglycaemia
weight gain or anorexia
nausea, heartburn
weakness or numbness of the extremities
what is the MOA of sulphonylureas and secretagogues
act similar to glucose as they inhibit the ATP sensitive K+ channel, but they bind to the SUR portion. this depolarizes the channel and allows influx of Ca++ which stimulates the release of insulin
these oral hypoglycemic enhances secretion of insulin similar to that as sulfonylureas. it has a rapid onset of action and short duration. is generally taken before a meal because if a meal is skipped or delayed it can cause hypoglycemia
meglitinides (nateglinide and repaglinide)
this oral hypoglycemic agent decreases hepatic glucose production
biguanides (metformin)
what is the MOA of biguanides (metformin)
blocks gluconeogenesis in the liver. increases insulin sensitivity in the muscle and fat by sensitizing the insulin receptors. promotes glucose uptake by skeletal muscle.
these drugs are good agents for restoring glucose into normal or non-diabetic range without causing hypoglycemia
thizolidinediones (e.g. pioglitazone)
what is the MOA of thiazolidinediones
agonists of PPAR-gamma. increases the sensitivity of tissues (muscle and adipose) to insulin. reduces insulin resistance
what are some side effects of thiazolidinediones
weight gain, edema, GI, h/a, increased respiratory infections
what is the MOA of alpha-glucosidase inhibitors (acarbose)
competitive inhibitor of intestinal alpha-glucosidase (enzyme that breaks down disaccharides). delays absorption of carbohydrates from the gut. reduces postprandial glucose rise
what are some side effects of alpha-glucosidase inhibitors
GI!!! may wanna stay away from this drug
