Insulin & Oral Antidiabetics Flashcards
Is insulin a pancreatic catabolic hormone that promotes nutrient use?
No- anabolic and promotes storage
What three things increase pancreas beta cells release of insulin?
- Vagal innervation
- GI hormones
- Glucose, A.A.
What are insulins effects on liver?
increase glycogen and trig. synthesis,
inhibits glyogenolysis, glycogenesis and ketogenesis
What are insulins effects on muscle?
increase glucose and amino acid uptake. Increase glycogen and protein synthesis.
What is insulins effect on adipose tissue?
increase triglyceride storage and inhibits lipolysis
What if anabolic reactions can’t take place?
anabolic/catabolic balance is disturbed and catabolic prevail
The metabolic changes that occur in DM are similar to those that occur during what?
fasting [if you have nothing to eat, you use and eventually deplete your stored nutrients.]
What is the etiology of diabetes mellitus?
decrease insulin production or increase in insulin resistance
Review epidemiology of diabetes
8% incidence, 20 million people in 2011, $245 billion
What percentage are insulin dependent diabetes cases? what are they due to? detection? what age?
- 5-10%
- autoimmune destruction of beta cells
- very low undetectable insulin
- diagnose before 30
What percentage is not insulin dependent? due to what? insulin levels? insulin response? onset age?
- 90%
- decreased responsiveness
- subnormal
- blunted
5 usually over 40 and overweight
What is gestational diabetes due to?
steroid induced insulin resistance- 7% of pregnancies –mostly 3rd trimester
What drugs induce DM?
glucocorticoids or growth hormones
What are the 4 therapeutic approaches to Type 1 DM?
- insulin
- insulin and pramlintide
- diet
- exercise
What are the 4 therapeutic approaches to Type 2 DM?
- diet
- Exercise
- anti-diabetic drugs individually or in combo
- insulin
What are the 3 things we do for gestational diabetes?
- diet and exercise
- insulin. only FDA approved
- Some oral anti-diabetic drugs (sulfonylureas and biguanides)
What are the major complications of diabetes?
end-stage renal disease, heart disease, stroke, hypertension, blindness, peripheral neuropathy
What do sulfonylureas meglitides and nateglinide attack>
ATP sensitive K channels in the beta cells
What do biguanides do?
reduce hepative gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase, antagonize the actions of glucagon
What do thiazolidinediones act on?
PPARy in muscle, adipose, and liver
Incretins or inhibitors of incretin degradation effect what cells?
alpha and beta cells in pancreas
amylin analogs affect what cells?
alpha cells and CNS
What receptor do we try to affect in the kidney?
inhibitors of sodium glucose co-transporter
What does insulin form in concentrated solutions?
dimers and hexamers, but they are absorbed slowly when injected
What are the main differences from types of administered insulin?
rate of absorption, onset, and duration of action
how can we change rate of absorption?
mutation of amino acid residues, addition of components such as protamine, buffers in insulin
What are lispro, aspart, glulisine?
rapid acting insulin
What is regular crystalline insulin?
short acting
What is NPH??
intermediate acting (slower than regular) insulin
What are glargine and detemir?
long acting insulins
Continuouse insulin infusions usually use what type of insulin?
regular or rapid acting [ lispro, aspart, glulisine]
The effectiveness of insulin therapy can be enhanced with what?
amylins
The insulin secretagogues effect what receptor?
decrease K efflux in beta cells(lowered with increased ATP)
Do meglitinides or sulfonylureases have higher affinity for K channels?
meglitinides
What inhibits mitochondrial glycerophosphate dehydrogenase?
biguanides- actions take place in the liver leading to reduction of gluconeogenesis and thus hepatic glucose output
Does biguanides cause hypoglycemia and weight gain?
No, neither
What are the agonists for PPARy?
Thiazolidinediones- increase insulin sensitivity in target tissures
What do incretins do in pancreatic beta cells? alpha cells?
up insulin
down glucagon
[together decrease postprandial glucose]
What does amylin do?
inhibit glucagon secretion and has CNS-mediated anorectic effect
What is the only combination approved for type 1 diabetes?
insulin and pramlintide
