Insulin And Oral Diabetic Drugs

Front 1

what type of cell secretes glucagon?

Back 1

α cell

Front 2

why is important that the islet cells are well vascularized?

Back 2

keep well supplied with O2 and nutrients
carry away hormones

Front 3

why does it take a long time for diabetes to manifest?

Back 3

big reserve in pancreas - it holds 10x what the body needs

Front 4

most important regulator of insulin secretion?

Back 4

glucose

Front 5

sequence of events leading to insulin secretion?

Back 5

glucose uptake by GLUT2 to islet cells --> glycolysis to yield ATP --> closure of ATP sensitive K+ channels --> depolarization --> opening of voltage gated Ca2+ channels --> release of insulin

Front 6

enzyme that regulates insulin secretion?

Back 6

glucokinase

Front 7

where is glucokinase found?

Back 7

β cells
liver

Front 8

insulin structure?

Back 8

A peptide and B peptide linked by 2 disulfide bonds between cysteines;
well conserved in mammals

Front 9

insulin receptors?

Back 9

heteromer with 2 α subunits and 2 β subunits

Front 10

α subunits of insulin receptors?

Back 10

extracellular
transmit signal to β subunit to activate downstream pathways

Front 11

β subunit of insulin receptor?

Back 11

tyrosine kinase that undergoes autophosphorylation and phosphorylates IRS (insulin receptor substrate)

Front 12

function of IRS?

Back 12

when phosphorylated, activates PI3 kinase and MAPK pathways

Front 13

MAPK pathway?

Back 13

activated by insulin resulting in cell growth and differentiation

Front 14

PI3 kinase pathway?

Back 14

activated by insulin resulting in lipid synthesis and glucose/protein metabolism

Front 15

venous drainage of islet cells and consequence?

Back 15

secreted into portal circulation direct to the liver;
50% destroyed in one pass;
liver sees higher insulin concentration

Front 16

kidney metabolism of insulin and consequence?

Back 16

~30% of endogenous
~60% of exogenous
adjust dosage with renal failure

Front 17

general effects of insulin?

Back 17

anabolic

Front 18

insulin effects on carbohydrates?

Back 18

increased glycogen synthesis
increased glucose uptake in fat, liver, muscle
reduced gluconeogenesis in liver
reduced blood glucose

Front 19

which tissues does insulin caused increased glucose uptake?

Back 19

fat
liver
muscle

Front 20

insulin effects on fats?

Back 20

increased fatty acid and TG synthesis
reduced serum TG
reduced lipolysis

Front 21

insulin effects on protein?

Back 21

increased protein synthesis
reduced protein breakdown
increased amino acid uptake

Front 22

type 1 DM presenting symptoms?

Back 22

polyuria
polydipsia
polyphagia with weight loss
decreased strength

Front 23

cause of type 1 DM?

Back 23

~50% genetic
~50% uncertain environmental

Front 24

type 2 DM?

Back 24

insulin resistance + β cell failure
early symptoms minimal or absent
progressive disease
elevated insulin levels

Front 25

when in history was there a decrease in type 2 DM?

Back 25

WWII

Front 26

incidence of gestational diabetes?

Back 26

4% of pregnancies
multiple episodes have higher future risk

Front 27

mechanisms of diabetic complications?

Back 27

free radicals
advanced glycation end products
signal transduction screw up

Front 28

significantly reduces diabetic complications?

Back 28

tight blood glucose control
blood pressure
serum lipids

Front 29

diabetic complications?

Back 29

cardiovascular
blindness
renal failure
neuropathy

Front 30

leading cause of blindness?

Back 30

DM

Front 31

cardiovascular diabetic complications?

Back 31

atherosclerosis
infarcts and strokes
heart failure
peripheral vascular disease
(tight control is not as preventative)

Front 32

short term treatment goals of diabetes?

Back 32

relieve hyperglycemia
overcome acute ketoacidosis
promote normal growth in children

Front 33

long term treatment goals of diabetes?

Back 33

decrease complications
limited by patient compliance
limited by risk of hypoglycemia

Front 34

major indications for insulin?

Back 34

type 1 DM
type 2 DM when diet alone or oral agents fail or during periods of illness or stress
diabetes during pregnancy

Front 35

differences between insulin preparations?

Back 35

all act on same receptor
differ in speed and duration of action
sold at same concentration (U100)

Front 36

problems with insulin therapy?

Back 36

lipodystrophy and allergy at injection site
hypoglycemia

Front 37

limiting factor in tight blood glucose control?

Back 37

hypoglycemia

Front 38

hypoglycemia?

Back 38

rapid fall in blood glucose detected by hypothalamus and leads to increased epinephrine production which promotes glycogenolysis;
increased heart rate;
palpitation;
sweating;
hunger;
weakness;
repeated episodes reduces hypoglycemic response and prevent patient from recognizing need to treat with oral glucose

Front 39

causes of hypoglycemia?

Back 39

overdose of insulin
exercise
skipped meals

Front 40

treatment for hypoglycemia?

Back 40

oral or iv glucose

Front 41

diabetic ketoacidosis?

Back 41

increased lipolysis and conversion of fatty acids to acidic ketones

Front 42

pathophysiology of DKA and hyperosmolar coma?

Back 42

dehydration
acidosis
electrolyte imbalance

Front 43

acidic ketones?

Back 43

acetoacetoacetate
β hydroxybutyrate

Front 44

indications for oral diabetic therapy?

Back 44

type 2 DM not controlled by diet alone/exercise or patient cannot or does not want to use insulin

Front 45

sulfonylureas?

Back 45

insulin secretagogues
close ATP sensitive K+ channels leading to depolarization and stimulation of more insulin release

Front 46

adverse reactions and precautions for sulfonylureas?

Back 46

hypoglycemia - may last a while due to long half life;
loss of efficacy due to decreasing numbers of β cells

Front 47

replaginide and nateglinide?

Back 47

insulin secretagogues
short duration of action - taken prior to meals

Front 48

metformin?

Back 48

biguanide
increase tissue glucose uptake

Front 49

metformin advantages?

Back 49

does not depend on insulin secretion
does not produce hypoglycemia
works well with other oral agents
renal inactivation, short duration

Front 50

metformin adverse effects?

Back 50

gi distress
promote lactic acidosis - potential increased by alcohol, tissue hypoxia, overdose, or renal failure

Front 51

contraindication for metformin?

Back 51

alcoholic

Front 52

thiazolidinediones?

Back 52

antidiabetic
reduced insulin resistance via PPARγ

Front 53

PPARγ?

Back 53

reduced circulating lipids
reduced expression of cytokines promoting insulin resistance (TNFα)
increased expression of cytokines that increase insulin sensitivity (adiponectin)

Front 54

thiazolidinediones adverse effects?

Back 54

weight gain
fluid retention promoting CHF
hepatotoxicity

Front 55

contraindications for thiazolidinediones?

Back 55

pregnancy
hepatic failure
heart failure

Front 56

α glucosidase inhibitors?

Back 56

inhibit α glucosidase in gut to slow intestinal absorption of glucose from polysaccharides, lowering postprandial glucose peaks

Front 57

why fewer systemic side effects with α glucosidase inhibitors?

Back 57

most of the drug stays in the gut

Front 58

clinical use of α glucosidase inhibitors?

Back 58

combination with other oral drugs

Front 59

pramlintide?

Back 59

injectable analogue of amylin
reduces postprandial glucose in type 1 and 2 DM

Front 60

amylin?

Back 60

beta cell product secreted with insulin

Front 61

incretins?

Back 61

GLP-1
GIP

Front 62

incretin actions?

Back 62

increased insulin secretion
increased β cell growth
reduced glucagon secretion
slower gastric emptying
reduced appetite

Front 63

unique action to incretins?

Back 63

increased β cell growth

Front 64

exenatide?

Back 64

GLP-1 analogue
injected SC
very beneficial when combined with sulfonylureas or metformin

Front 65

adverse effects of exenatide?

Back 65

gi
rare fatal pancreatitis

Front 66

sitagliptin?

Back 66

DDP IV inhibitor - block GLP-1 degradation
oral agent that theoretically has benefits of injectable exentatide

Front 67

insulin secretagogues?

Back 67

sulfonylureas
repaglinide
nateglinide

Front 68

insulin independent glucose uptake promoter?

Back 68

metformin

Front 69

insulin sensitizors?

Back 69

PPARγ agonists (thiazolidinediones)

Front 70

delayed gi uptake?

Back 70

acarbose
miglitol
(α glucosidase inhibitors)