(5) GI & Endo: DM (2.1-2.2) Flashcards
Stimulation of what adrenergic receptor increases insulin secretion?
β2
How does glucose induce insulin release?
Closes ATP dependent K+ channels
↑ Glucose
⇒ ↑ Aerobic respiration
⇒ ↑ ATP
⇒ Closure of ATP gated K+ efflux channels
⇒ ↑ Membrane voltage
⇒ Opening of voltage gated Ca2+ channels
⇒ Ca2+ influx
⇒ Exocytosis of insulin
Name 2 proteins secreted from the same vesicle as insulin
(1) C-peptide
(2) Amylin
* (Note: C-peptide is not included in exogenous insulin ∴ C-peptide can be used as a marker for insulin poisoning)*
What class of receptor is the insulin receptor?
Intrinsic receptor tyrosine kinase
What receptor does insulin upregulate in peripheral tissue?
GLUT4
What metabolic changes occur after insulin binds its receptor?
(1) ↑ Glycogen
(2) ↑ Anabolism
(3) ↑ TG synthesis
How does insulin decrease serum K+ levels?
↑ Activity of Na+/K+ ATPase
(Predominantly in skeletal muscle)
What are the rapid-acting, short-duration insulin analogs?
(1) insulin Glulisine
(2) insulin Aspart
(3) insulin Lispro
What insulin analogs are used for control of postprandial glucose spike?
(1) insulin Glulisine
(2) insulin Aspart
(3) insulin Lispro
What are the intermediate-acting insulin analogs?
(1) Regular insulin
(2) NPH insulin
What is the only insulin analog available for IV administration?
Regular insulin
Treatment: Diabetic ketoacidosis
IV regular insulin
(Remember to add K+ to avoid hypokalemia)
What hormone can be used to treat hyperkalemia?
Insulin
(Remember to add glucose to avoid hypoglycemia)
What are the long-acting insulin analogs?
(1) insulin Detemir
(2) insulin Glargine
* (G-_LARGE_-ine is the longest acting insulin analog)*
What is the most common complication of insulin therapy?
Hypoglycemia
(Duh!)
MOA: Sulfonylureas
Inhibit ATP-dependent K+ channels
- (↑ Endogenous insulin ∴ ↑ C-peptide)*
- (↑ Endogenous insulin ∴ Only treats T2DM)*
Suffix: First-generation sulfonylureas
“-amide”
Suffix: Second-generation sulfonylureas
“-ride”
What second-generation sulfonylurea has the shortest duration of action?
Glipizide
Indication: Meglitinides
T2DM
Other than hypoglycemia, what is a common side effect of sulfonylureas and meglitinides?
Weight gain
What class of diabetes drugs can cause a disulfiram-like reaction?
First-generation sulfonylureas
Suffix: GLP-1 analogs
“-tide”
What are the physiologic actions of GLP-1?
(1) ↓ Glucagon secretion
(2) Delay gastric emptying
* (Satiety, ↓ Glucagon release, Inhibit gastric emptying)*
MOA: “-gliptin” drugs
Inhibit DDP-4
(And ∴ degradation of GLP-1. Gliptins be GLP-liftin)
What class of drugs increases levels of endogenously secreted GLP-1?
Gliptins
(Gliptin = GLP-Liftin’)
Adverse Effects (2) : DPP-4 inhibitors
(1) Nasopharyngitis
(2) URTIs
Which diabetes drugs do not cause hypoglycemia?
(1) GLP-1 analogs
(2) DDP-4 inhibitors
* (∵ Effects are glucose-dependent, diminishing as glucose levels approach normal)*
Can GLP-1 agonists treat T1DM?
No
Adverse Effect: GLP-1 inhibitors
Pancreatitis
Name an enzyme that Metformin inhibits and one that it activates
(1) Inhibits: mGPD
(2) Activates: AMP Kinase
* (mGPD = Inhibits mitochondrial enzyme glycerophosphate dehydrogenase)*
* (AMPK ↓ Gluconeogenesis and ↑ Insulin sensitivity)*
Other than affecting gluconeogenesis, what is the mechanism of Metformin?
↑ Insulin sensitivity
(Other aspects include ↓ intestinal absorption of glucose)
Adverse Effects (2) : Metformin
(1) Lactic acidosis
(2) GI Issues
How is Metformin excreted?
Renal
(Unaltered and in active form)
Name a diabetes drug which may cause weight loss
Metformin
Suffix: Thiazolidinediones
“-glitazone”
MOA: Glitazones
PPAR-γ ligand
(∴ ↑ Insulin sensitivity and fatty acid oxidation)
How do glitazones ↓ serum triglyceride levels?
(1) ↑ Fatty acid oxidation
(2) ↑ Differentiation of adipocytes
Name 2 proteins that glitazones upregulate
(1) Adiponectin
(2) GLUT4
Adverse Effects (4) : Glitazones
(1) Weight gain
(2) Peripheral edema
(3) ⇒ Heart failure
(4) ↓ Bone mineral density
What are the physiologic effects of Amylin?
(1) ↓ Gastric emptying
(2) ↓ Glucagon
What drug can be used to treat T1DM and T2DM but is not an insulin analog?
Amylin
Adverse Effects (2) : Amylin
(1) Hypoglycemia
(2) GI upset
Name 2 α-glucosidase inhibitors
(1) Acarbose
(2) Miglitol
What is the mechanism of α-glucosidase inhibitors in treating diabetes?
↓ Intestinal glucose absorption
Why are α-glucosidase inhibitors infrequently prescribed?
Severe abdominal side effects
(Undigested GI sugars ∝ Symptoms of lactose intolerance)
Suffix: SGLT2 inhibitors
“-flozin”
MOA: “-flozin” drugs
Inhibit SGLT2
(In proximal convoluted tubule ∵ that’s where everything is reabsorbed)
Adverse Effects (3) : SGLT2 inhibitors
(1) ↑ Frequency of urination
(2) UTIs
(3) ↑ Risk of vaginal candidiasis
(↑ Urination ⇒ Hypotension)
Contraindication: SGLT2 inhibitors
Renal sufficiency
