Type I Diabetes Flashcards
What is the cause of Type I diabetes?
Insulin deficiency due to selective beta-cell destruction
What natural tendency of insulin acts as a barrier to absorption?
Self-association and the formation of hexamers
What is “regular insulin” in terms of conventional insulin formulations and the treatment of Type I diabetes?
Recombinant DNA technology from the human proinsulin gene
What insulin formulation has the highest variability of absorption?
Neutral protamine hagedorn (NPH)
Aspart, Glulisine, and Lispro are all what type of insulin formulation?
Rapid acting insulin analogues
Glargine, Detemir, and Degludec are all what type of insulin formulation?
Long acting insulin analogues
What changes are made to lispro, aspart, and glulisine?
Lispro - 28proline and 29lysine are reversed, mimicking insulin-like growth factor 1
Aspart - 28proline is changed into aspartic acid
Glulisine 29lysine is changed into glutamic acid and 3asparagine is changed to lysine
Why is Glargine prepared in an acidic solution?
Addition of two arginine moieties at the carboxylic end of the B chain of insulin shift the isoelectric point, causing the insulin analog to precipitate out at physiologic pH
What changes do Glargine, Detemir, and Degludec contain?
Glargine - addition of arginine to B chain and change from asparagine to glycine in A chain (more stable in acidic solution)
Detemir - 30threonine is removed and myristic acid is attached
Degludec- 30threonine is removed and hexadecanedioic acid is attached
How does insulin affect glucose uptake?
Activation of Akt and translocation of GLUT4 to the plasma membrane of muscle and fat cells increases glucose uptake
How does insulin affect glycogen synthesis?
Inhibition of GSK3 prevents phosphorylation of GS, allowing for synthesis of glycogen
How does insulin affect gluconeogenesis?
Inhibition of FoxO1 reduces the transcription of gluconeogenesis genes in the liver
How does insulin affect protein synthesis?
Activation of mTOR causes signaling molecules to turn on protein synthesis (in muscle)
How does insulin affect lipolysis and ketogenesis?
Activation of Akt leads to increase activity of phosphodiesterase 3B, which degrades cAMP and reduces lipolysis and therefore decrease ketogenesis
Insulin activates acetyl CoA carboxylase in the liver, which produces malonyl CoA, inhibiting fatty acid oxidation and promoting their biosynthesis
What are adverse effects seen with insulin use?
Hypoglycemia*
Localized lipodystrophy (loss or hypertrophy of fatty tissue at the site of injection)
Insulin allergy from localized histamine release (rare)
Insulin resistance from anti-insulin (IgG) antibodies (rare)
Weight gain*
