Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

101 Cards in this Set

  • Front
  • Back
what secretes insulin?
pancreatic beta cells
what are the two main cells of the pancreatic islet?
beta cells and alpha cells
what do alpha cells do?
secrete glucagon
what is the effect of insulin on glucagon secretion?
inhibitory so in diabetics with decreased or absent insulin secretretion(ie type 1) there will be increased glucagon which is a needed factor in ketoacidosis and that is why ketoacidosis is more commoni in type one DM
what happens if you lose some of your beta cells?
nothing normal healthy people have a huge reserve of beta cells you have to lose a lot before you become diabetic
what is the main function of thepancreas?
secretion of enzymes needed in digestion espeacially of fat. only 2-3% of pancreatic mass comes from islets
what is important about the blood supply of the pancreate islets?
they are part of portal circulation, they see the blood right after its absorbed the nuetrients from digestion and before that blood reaches the liver. So they are able to respond very quickly to with hormone secretions in response to a meal and those secretions go very quickly to the liver.
what is important about the blood flow from the islets to the liver and injecting insulin?
normally bc the liver is the first organ to see the secretions from the pancreas, the level of insulin seen by the liver is several times higher than the rest of the body.

however in diabetics who inject insulin that insulin does not have a higher concentration seen by the liver.
what is the glucose transporter of the beta cell?
what is the most important regulator of insulin secretion in normal people?
are there intracelluar receptors for glucose in the beta cells that respond to high levels of glucose?
no, glucose must be metabolized beofre it can act to increase insulin release.
what are the fuels that regulate insulin release?
what must happen to glucose in the beta cell for it to be metabolized?
it must be phosphoralated by glucokinanase
what is unique about the km of glucokinase?
it is very close to the physiologic concentration of glucose so when glucose concentration goes up it is not saturated the metabolism goes up.
what is the chain of events that leads to insulin secretion in the beta cell?
glucose uptake by GLUT2
glucose phosphorylation by glucokinase
glucose metabolism generating ATP
increaced ATP/ADP ratio closes ATP sensitive potassium channel
this causes depolarization
depolarization opens voltage gated calcium channel
calcium influx is what signals the release of insulin containing vesicles that migrate and excrete insulin
what is the structure of insulin?
dipeptide linked together by two disulfide bonds
what are the parts of the insulin receptor?
and what doe they do?
2alpha subunnits- act as actual receptor for insulin

2 beta subunits- these are tyrosine kinases that span the membrane and autophosphoralate in response to alpha subunit binding insulin they also phosphorylate insulin receptor substrate proteins(IRS)
what are the actions of the IRS proteins?
IRS proteins activate phosphotidylinositol 3 kinase pathway and the MAP kinase pathway.
what is the overall function of the map kinase pathway?
promotes cell growth and differentiation
what are the two enzymes phosphorylated by PI3Kinasae? and what are their functions?
AKt-glucose/protein metabolism

PKClambda- lipid synthesis
what is the main mechanism of insulin action in liver/fat/muscle?
insulin binds insulin receptor
insulin receptor stimulates IRS
IRS stimulates PI3 Kinase
PI3 kinase stims Akt
Akt phosphoylates vessicles containing GLUT4 glucose channels
those vessicle insert the GLUT4 into the plasma membrane and increase uptake of glucose.
What is the difference in metabolism of endogenous insulin vs injected insulin?
endogenous insulin secreted into portal cirulation with about 50% destroyed in first pass through the liver before even reaching the majority of tissue. Only 30% is metaabilized by the kidney

injected insulin does not pass through the liver first and as such the kidney plays a much larger role metabolizing 60% of injected insulin.
What is the half life of endogenous insulin?
what are the main tissues whose glucose uptake is insulin dependent/
fat, liver, muscle

brain can take up glucose just fine withou any insulin
why are type 1 DM patients skinny with low muscle mass?
one of the effects of Insulin is protien synthesis. so no insulin = no protein and muscle building
what are the hormones produced by adipose?
leptin-stims satiety

adiponectin- enhances insulin response

TNF-alpha- stimulates inflammation which promotes insulin resistance
what percent of pregnancies develope gestational diabetes?
what is the drug of choice for treatment of gestastional diabetes?
what complication of DM is not really controlled by good glucose control?
cardiovascular -atherosclerosis
infarcts and strokes
heart failure
periperal vascular disease

these are the leading cause of death in DM
what complications of DM are reduced with good glucose control?
renal failure
what are the treatment goals in DM short term and long term?
short term-
relieve hyperglycemia
overcome acute ketoacidosis

long term-
aim to decrease complications with good blood glucose control.

limited most by pt. compliance, requires multiple daily injetions and frequient finger sticking

limited by risk of hypglycemia
what is the issue with tight blood glucose control?
poor glucose control leads to problems with blindness/renal/neuro stuff but it does not increase mortatlity. there is some evidcence that suggest that tight glucose control (keeping blood glucose as low as normal population) has increased risk of hypoglycemia, and as a result may actually lead to increased mortality.

This means that its possible that you don't want to have glucose control be to tight or too loose. possilby best to keep glucose as slithglty above normal population but below level that can lead to the dangerous DM complications.
Which group is likley to be most in danger with tight blood glucose control?
elderly have bad reactions with hypoglycemia
what are the three indications for use of insulin in DM?
type 1 diabetes
type 2 DM when diet alone or oral agents fail or during periods of illness or stress
gestational diabetes
how can you test beta cell function in DM who is taking insulin?
check for C-peptide
what are the differences in the types of insulin?
the rate of absorption: this affects duration of action and time till onset
what slows the rate of absorption of insulin?
self aggregation or binding to protiens like protamine
what is the only insulin that can be given intravenously?
regular human insulin
what are the 4 classes of insulin drugs?
rapid acting- fastest
short acting- second
intermediate acting- third
long acting- slowest
What concentration are almost all insulins sold at?
how is insulin administered?
subcutaneous injection or pump

regular insulin can be given IV for emergency
what emergency will warrent IV insulin?
what are the rapid insulins?
insulin lispro, aspart, glulisine
what are the short acting insulins?
regular insulin
what are the intermediate acting insulins?
what are the long acting insulins?
insulin determir
insulin glargine-longest
how long after injection do rapid acting work and for how long?
almost 1 hour till peak onset decent action at 15mins

with 2-3 hour duration
what is the normal insulin regimen for diabetics?
rapid or short acting injection prior to each meal, with one long acting taken at begining of day.
what are the three concerns with insulin therapy?
lipoddystrophy-atrophy of subcutaneous fat at injection site- rare now

allergy- rare now with pure insulins

hypoglycemia- main concern by far
what are the main issues of hypoglycemia?
confusion, coma, seizure,and death most common in patient with very tight control
what are the symptoms of hypoglycmeia prior to confusion, coma, siezure? and what is the cause?
sympathetic symptoms: increased HR, palpatations, sweating, hunger, and weakness.

rapid fall in BG detected by hypthalamus and leads to increased epinephrine production which promtes glycogenolysis
What are the normal causes of hypoglycemia when on insulin therapy?
overdose, excerise, skipped meals
what is the treatment of hypoglycemia?
oral or IV glucose
what is a problem with repreated hypoglyucemic episodes?
reduced hypoglycemic response means less symptoms and pt may not recognize the need for treatment.
what is the treatment for diabetic ketoacidosis and hyperosmolar coma?
IV regular insulin
electrolyght and fluid replacement
when are the antidiabetic drugs other than insulin indicated?
symptomatic type 2 diabetes not controlled by diet alone, and pateint cannot or does not want to use insulin
what is the actions of the sulfonylureases?
insulin secretagogues
closes beta cell potassium channels leading to depolarization and sitmulation of more insulin secretion.
what are the first gen sulfonylureas?
tolbutamide, tolazamide, chlorpropamide
what are the second gen sulfonylureas?
glyburide, glimepiride, glipizide
what is hte MOA of the second gen sulfonylureas?
same as 1st gen but higher potency which allows once a day dosing
what is a contraindication of sulfonylureases?
all metabolized in liver and contraindicated in liver failure
what are the adverse reactions of the sulfonylureases?
hypoglyciemia can occur and last several days increased risk if hepatic disease present

decreased efficacy as type 2 DM progresses and beta cells become exhausted and fail to respond
what is MOA of replaginide and nateglinide?
same as the sulfonylureas except short duration of action
what is an advantage of repliginide and nateglinide over the sulfonylureases?
due to short duration if they cause hypoglycemia its shorter duration and when hypoglycemic these drugs are inhibited so their actions stop.
What is the first line drug treatment for all type 2 diabetics that cannot get by on diet and excersise alone?
What class does metformin belong to?
biguanides, only member still available.
what it the MOA of metformin?
increase tissue glucose uptake and reduce hepatic gluconeogensis

PROBABLY by activation of AMP kinase
What are the big benifits of using metformin?
delays or prevents onset of type 2 diabetes in prediabetics

does not depend on insulin secretion

does not preoduce hypoglycmeia
How is metformin metabolized?
Renal inactiveation with short duration of action
what are the adverse effects of metformin?
GI distress common at start of therapy
can promote lactic acidosis by uncertain MOA, the potential for this is increased by alcohol, tissue hypoxia, and overdose or renal failure
what is the MOA of thiazolidinediones?
reduced insulin resistance

acts through PPARgamma recepto which alters gene expression and promoetes genes involved in lipid storage, reducing circulating lipids, reduces expression of cytokines(TNFalpha), and increases expression of cytokins that increase insulin sensitivity.(adiponectin)
what are the two thiazolidinediones?
rosiglitazone and pioglitazone

only pioglitazone is still on market
what is the main reason thiazolidinedones are not used as often as they used to be?
weight gain fluid retention that can promote congestive heart failure and rare hepatotoxicity.
when are thiazolidineodones contraindicated?
pregnancy, hepatic failure, and heart failure patients
what were some benifits of thiazolindinedones?
very little hypoglyemia
delayed onset of DM type 2
what is the MOA of alpha-glucosidase inhibitiors?
inhibits alpha glucosidase in the guts and slows intestinal absorption of glucose from polysacchardies, lowering postprandial glucose peaks
what are the two Alpha-glucosidase inhibitors?
Acarbaose and miglitol

acarbose used more often
what is the adverse effects of alpha glucosidase inhibitors?
moderate GI issues little else because it doesn't leave the GI tract
what is the use of the alpha glucosidase inhibitors?
only has modest potency for lowering blood glucose main function is to reduce post prandial glucose spikes so usually taken as a combination drug with other oral medications
what is the MOA of pramlintide?
injectable analogue of amylin

slows GI absorption and reduces appetis and reduces glucagon secretion
what is amylin?
when beta cells release vessicles they contain insulin, c-peptide, and amylin

it was once thought that amylin was not biologically active but now we know it is. and loss of amylin release in diabetics is part of the cause of their issues.
what is the adverse effect of pramlintide?
what is a nice thing about who can use pramlintide?
only oral medication that can help type one diabetics as well as type 2
what are the effects of incretins?
they are secreted by the gut in response to food to aid in insulin sectreion, increased beta cell growth, reduced glucaogn secretion, slower gastic emptying, reduced appetitie
what are the incretins and where are they released?
GLP-1- released by L cells in the illeum

GIP- released by K cells in the jejunum
what is exenatide?
GLP-1 analogue
must be injected SC
what it he half life of exenatide?
2.4 hours given twice a day
what is exiciting about exenatide?
in animal models of type 1 diabetes exenatide can reverse diabtes if immuse response is suppressed.
what are the adverse effects of exenatide?
GI and rare fatal pancreatitis
what are the DPP IV inhibitors?
sitagliptin- blocks GLP1 degradation
how is stagliptin given?
what is the ending of the name for all DPP IV inhibitors?
what is the MOA of dapgliflozin?
inhibits SGLT2 tubular glucose transportoer and lowers blood glucose and weight
what is an adverse effect of dapgliflozin?
increased urination
What is the most effective therapy for type 2 DM?
combingin more than one agent with DIFFERENT MOA

weight loss is almost always beneficial as is excersise.
what is the major action of GLP-1?
stimulates glucose dependent insulin secretion
Which drug is a component of the saliva of the gila monster?
what enzyme breaks down GLP-1?
dipeptidyl peptidase IV
what is the difference btw GLP-1 and exenatide?
exenatide is resistand to the effects of dipeptidiyl peptidase IV
what is a disadavantage of GLP-1?
short duration of action(2-3mins half life) due to rapid degredation by DPP IV
what is a drug that is an analogue of GLP-1 but has longer duration of action due to binding albumin