Welch Diabetes Flashcards
What is the functional unit of the pancreas?
islets of Langerhans
What are the types of cells in the islets of Langerhans? What does each secrete?
Alpha cells - glucagon
Beta cells - insulin
Which peptide is cleaved in maturation of insulin?
C-peptide
What effect does insulin have on carbohydrate, protein, and fat pools?
Carbohydrate:
- inhibits glycogen synthetase to store glucose as glycogen
- increases gluco-1-phosphatase to increase energy utilization
- inhibits gluconeogenesis
Protein
- increases break down of protein to amino acids to be released
Fat
- Decreases lipase activity and allows for storage of fat
What happens if the body lacks insulin in terms of gluconeogenesis and lipase activity?
Increased gluconeogenesis means more urea excretion (azoturia)
Increased lipase activity leading to more FFA to be converted to ketones
Can glucose enter cells without insulin? Which cells are found to have them?
Yes, if there are GLUT-2 receptors present. Beta cells in the pancreas have them
How does glucose regulate the amount of insulin?
If glucose enters the beta cell, ATP is generated which will bind to ATP sensitive K channels that will close it and depolarize the cell by increase intracellular calcium. This will secrete more insulin
Is the ATP sensitive potassium channel on the outside or inside of the cell? SU receptors?
ATP: inside
SU: outside
What is the MOA of biguanides? sulfonyl ureas? TZDs?
Biguanides - decrease hepatic glucose production (AMPK stimulators)
Sulfonyl urea - increase insulin secretion
TZD - increase insulin sensitivity
What is the MOA of DPP-4 inhibitors? GLP-1 agonists?
DPP-4 inhibitors - increases GLP-1 and GIP concentrations
GLP - 1 agonists - increases insulin concentrations by glucose dependent mechanisms, decreases glucagon, decreases gastric emptying
Other than insulin desensitivity, what other aspect contributes to TDM2?
- Reduced beta cell response to high glucose concentrations
- Elevated glucagon
- Impaired secretions of incretin hormones
What is IAPP? It’s role in Beta cell function?
Islet amyloid polypeptide
- too much of it will damage Beta cell
Why are GLP-1 proteins so short-lived?
Degraded by DPP-4
What is Liraglutide?
A long-acting GLP-1 analogue (incretin mimetic)
What is Byetta?
An incretin mimetic that suppresses glucagon secretion
When prescribing Januvia, what you must consider regarding blood glucose?
BG must be elevated in order for this to work
Which class of drugs are considered to be a pancreatic secretagogue?
Sulfonyl ureas
What is the MOA of meglinitides?
Same as SU but at a slightly different binding site on SUR
What are some 1st generation SUs? 2nd generation?
1st generation: Orinase, Tolinase
2nd generation: Diabeta
What are some side effects and ADRs associated with metformin?
Nausea, cramps, diarrhea, and lactic acidosis
What are some side effects of alpha-glucosidase inhibitors?
Diarrhea, and flatulence
Which receptors does TZDs work on? What is the MOA of TZDs?
Peroxisome Proliferator-activated receptors (PPARy)
- Lowers blood glucose levels by improving target cell response to insulin
- Lowers levels of FFA
What is the MOA of SGLT2 inhibitors?
NEEDS RENAL ADJUSTMENT
Decrease hyperosmolar blood (glucose concentration)
Describe the components of the insulin receptor. Which part does insulin bind to?
What does the unbound part of the receptor responsible for?
The receptor consists of beta and alpha part. Insulin binds to the alpha section.
The beta region activates intrinsic tyrosine kinase activity which autophosphorylates the receptor to activate of cellular
What is somatostatin MOA?
Somatostatin binds to receptors on pancreatic beta cell that blocks voltage gated Ca++. Blocks insulin secretion
