Diabetes and insulin resistance Flashcards
Briefly describe 2 types of diabetes mellitus.
1) Early onset, destruction of β-cells.
2) Adult onset, insulin resistance due to β-cell overload and β-cell exhaustion.
What is the major mechanism of the chronic complications of diabetes mellitus?
Advanced glycation end-products (AGEs): Basically sugar placks in the blood vessels. Organs with small blood vessels will have the most damage (kidney, peripheral nerves, eyes, heart).
Briefly describe the mechanism of insulin secretion from pancreatic β-cells.
Insulin is stored in vesicles. Cells export the insulin out of the cell via depolarization (which happens when there’s too much glucose) driven fusion with the membrane.
List the mode of actions of diabetes drugs.
1) Increase insulin secretion (sulfonylurea/glyburide, meglitinides)
2) Increase insulin sensitivity (Thiazolidinediones - TZD: glitazones)
3) Decrease glucogenesis (Biguanides: metformin)
4) Decrease glucose absorption (α-glucosidase inhibitors: acarbose)
What is linkage disequilibrium in GWAS analysis?
The non-random association of alleles at two or more loci in a general population. When alleles are in linkage disequilibrium, haplotypes do not occur at the expected frequencies.
What is the fetal metabolic reprogramming hypothesis?
Epigenetic modifications to DNA that can alter metabolism based on environmental factors can be inherited.
Thrifty genes: leptin (satiety hormone produced in adipocytes)
List 3 effects of insulin on the target cells.
1) Increase in cellular uptake (glucose, amino acids, K+ ions). Translocation of transporters (GLUT4) to plasma membrane.
2) Increase in synthesis of glycogen and increased cell lipid storage (esterified lipids)
3) Decrease in breakdown of gluconeogenesis/glycogenolysis (breakdowns glucose into glycogen), lipolysis, and autophagy.
What is PIP3, and how does it mediate insulin signaling?
Phosphoinositol (PI) molecule that has been phosphorylated at 3 sites by PI3K. PI3K is activated by insulin receptor.
PIP3 can trigger signaling cascades that affect transcription.
List 2 mediator molecules of insulin resistance that are produced in adipose cells.
1) TNF
2) IL-6
3) Non-esterified free fatty acid
Which anti-diabetic drug increases insulin sensitivity, and which transcription factor does it activate?.
TZDs (-glitazones): activates PPARγ, thus increasing GLUT4 expression. Ultimately leads to increased cellular uptake of glucose, amino acids, K+ ions.
T/F: Calcium influx after membrane depolarization promotes the fusion of insulin containing vesicles to the plasma membrane.
True
What are the 3 acute complications that can result from diabetes
1) Diabetic ketoacidosis: When the body brekas down fat at a rate that is too fast. The liver processes the fat into a fuel called ketones, which causes the blood to become acidic.
2) Nonketotic hyperosmolar coma: High blood sugar results in high osmolarity without significant ketoacidosis. Symptoms include signs of dehydration, weakness, legs cramps, vision problems, and an altered level of consciousness.
3) Hypoglycemia: Low blood sugar
What is the role of miR-375 in pancreatic islet?
Inhibits glucose sensitive insulin secretion.
Higher miR-375 diminishes exocytosis of insulin.
What 2 receptors inactivate insulin receptors?
Toll-like receptors and TNFR (TNF receptor) in muscle or liver cells
What 3 cell types are you going target to treat for insulin resistance?
1) Adipocytes: inactivate using anti-inflammatory agents to control hyperlipidemia.
2) Liver and Muscle:
3) Intestine:
