Flashcards in Diabetes Deck (35):
Type 1 diabetes
Insulin dependent. Autoimmune destruction of beta-cells
Type 2 diabetes
Non-insulin dependent. Insulin secretion is unable to match increasing insulin demands due to insulin resistance.
What is insulin?
Peptide. T(1/2)=7 mins. Cleaved from pro-insulin in beta-cells. 2 insulin molecules can form a dimer and then a hexadimer around a Zn ion but must dissociate before binding to the insulin receptor.
Dimer. Receptor tyrosine kinase. Upon binding undergoes mutual phosphorylation that recruits substrate proteins such as insulin receptor substrate.
How is insulin secretion controlled?
Local intra-islet regulation. Also interactions between insulin and glucagon. Incretin effect.
What is the incretin effect?
Glucose in the gut stimulates release of incretins. Bind to GPCRs on beta-cells and stimulate an increase in cAMP. Cause an increase in the gain of glucose evoked insulin release.
How does glucose stimulate insulin release?
Taken up passively by GLUT-2 transporter into beta-cells. Phosphorylated to glucose-6-phosphate by glucokinase. Causes an increase in ATP/ADP ratio. Closes ATP-K+ channel. Causes depolarisation and opening of L-type calcium channels. Stimulates release of insulin containing vesicles
2 main treatments for type 1 diabetes?
Insulin replacement therapy and islet transplantation.
Follow Edmonton protocol. Require immunosuppression by diclizumab.
Insulin replacement therapy
Given subcutaneously to prolong action. Also given with zinc crystals.
Factors affecting s/c absorption
Prep of dose. Injection site. Changes at injection site.
Short acting insulin replacement therapy. 30 min onset. 2-4 hr peak. 8hr duration
Medium acting insulin replacement therapy. 1-2hr onset, 4-12hr peak, 16-24 hr duration.
Long acting insulin replacement therapy. 1-2hr onset. 4-12 hr peak. 20-35 hr duration .
Insulin analogue. 0-15 min onset, 1-2hr peak, 4-6 hr duration.
Defective control of plasma glucose concentration by insulin
What can cause type 2 diabetes?
Obesity. Receptor defect. Decrease in number of receptors. Beta-cell burnout - decrease in insulin sensitivity.
What are the 5 main treatment options?
Lifestyle (alcohol, smoking). Diet/exercise. Oral monotherapy. Oral combination therapy. Insulin.
4 main non-pharmacological treatments?
Statins. Fibrates. Resins. Orlistat.
Inhibit HMG-CoA reductase. The RL enzyme in the melavonate pathway of cholesterol synthesis
Fenofibrate. Increase HDL, decrease triglyceride levels and improve insulin resistance
Inhibits pancreatic lipase and decreases triglyceride absorption from the gut by 30%.
What does GLP-1 do?
Increases glucose evoked insulin secretion from beta-cells. Decreases postprandial glucagon production from alpha cells. Slows gastric emptying. Increases satiety and decreases appetite. Decreases hepatic output from liver.
Liraglutide and exanatide
Long lasting GLP-1 analogues
DPP IV inhibitor, decreases metabolism of GLP-1 but can cause upper respiratory tract infection, sore throat and diarrhoea.
Alpha glycosidase inhibitors
Reduce carbohydrate metabolism. Saccharides that act as competitive substrates for alpha-glucosidase enzymes in the brush border of the gut.
Oligosaccharide. Alpha glucosidase inhibitor.
Alpha glucosidase inhibitor. Monosaccharide.
Alpha-glucosidase inhibitor. Fewer side effects but Acarbose has higher efficacy.
Thiazodolinedione. Binds to PPAR(gamma) receptor that binds to retinoid X receptor and upregulates insulin sensitive genes. GLUT4, lipoprotein lipase, fatty acid transporter protein, fatty acid CoA synthase.
In combo with metformin - avandamet. In combo with glimepiride - avandaryl. Decreases excessive lipolysis and free fatty acid output. Decreases excessive hepatic glucose production. Directly decreases insulin resistance.
Biguanine. T(1/2)= 4-6 hrs. Decreases hepatic gluconeogenesis. Increases insulin sensitivity by increasing peripheral glucose uptake. Stimulates AMPK. Decreases glucose absorption from GI tract.