Ozcan 4-11, 4-14 Diabetes Flashcards
3 symptoms of diabetes
high blood glucose, excessive thirst of hunger, glucose in urine, fatigue, blurred vision, frequent urination
diagnosis of diabetes that must be confirmed at least twice
fasting plasma glucose(FPG) >126mg/dl, Oral Glucose Tolerance Test (OGTT)>200 mg/dl 2hrs after 75g dose, Random Plasma Glucose (RPG) >200mg/dl,
diagnosis of diabetes that can be performed once
HbA1c > 6.5%, insulin levels
insulin
discovered in 1912 by Fred Banting and Charles Best, consists of 2 chains (A=21aa & B=30aa) joined by 2 disulfide bridges, synthesized as preproinsulin (24aa signal peptide- B chain- C chain- A chain) processed to mature insulin in ER and Golgi. It is packed into insulin granules.
Islets of Langerhans
contain four cell types in the pancreas
alpha cells
secrete glucagon- signal the fasting state, make up 20% of the islet cells on the outter ring
beta cells
secrete insulin- signal the fed state, make up 70% of islet cells inside the ring of alpha cells
glucose-regulated insulin secretion steps
- Uptake and metabolism of glucose, leading to increased ATP levels, 2. Increased ATP/ADP ratio leads to closure of KATP channels causing 3. depolarization of the membrane, 4. Depolarization activates calcium channels causing calcium influx, 5. Rise in intracellular calcium causes insulin secretion from the granules into the blood stream.
defect of T2D
defects in insulin action and secretion
requirements for maintaining blood glucose
insulin release, glucose uptake by adipose and muscle cells, glucose output by liver cells
4 stages of T2D
insulin resistance, hyperinsulinemia, beta cell failure, hyperglycemia (T2D)
what do liver cells do in response to insulin
store glucose as glycogen
drug that stimulates insulin secretion, and its mechanism
sulfanylureas, meglitinides - they work by closing KATP channels; Glucagon-like peptide 1 (GLP1) -works on the beta cells directly
drugs that decrease insulin resistance
Thiazolidinediones (TZDs) pioglidazone- they activate nuclear hormone receptor PPAR gamma, metformin &biguanides -increase uptake by muscle, decrease gluconeogensis
drugs that delay digestion of carbohydrates and absorption of glucose
alpha glucosidase inhibitors- inhibit alpha amylase and alpha glucosidases