Diabetes Flashcards
How is diabetes characterised?
High levels of insulin, low concentration of receptors with high affinity
How was insulin first isolated?
Banting and Best tied off dog pancreas and accumulated extract
What is insulin?
A hormone that promotes glucose uptake for cells
Synthesised in pancreatic β-cells as preproinsulin
Hexamer
Part of the negative feedback chain with glucagon apposing it
What are the features of type I diabetes?
Typically adolescent onset
Genetic origin
Auto immune- pancreatic β-cells broken down
Loss of mass
Monozygotic concordance 30%
Associated with HLA
Familial
No obesity
What are the features of type II diabetes?
Maturely onset
May not require insulin
Can be modified by diet an insulin
Monozygotic 40-100%
No HLA association
Associated with obesity
What is glucagon?
Hormone synthesised in pancreatic α-cells
Increases gluconeogenesis, glycogenolysis and decreases lipogenesis
Controlled by ATP levels and glucose metabolism in mitochondria
How is glycolysis inhibited?
PKA synthesising phosphofructokinase-2
What components of β-cells are involved in glucose uptake?
Kir6.2 is a K+ channel and moves K+ out the cell.
Ca2+ channel
Glut-2 imports glucose
What effects does glucogon have in the brain?
Lower appetite
Higher satiety
What effects does glucogon have in the pancrease?
Higher insulin secretion
What effects does glucogon have in the liver?
Gluconeogenesis
Lipid breakdown
Less lipogenesis
What effects does glucogon have in the heart?
Higher heart rate
What effects does insulin have in the skeletal muscle?
increased glucose uptake
Glycogenesis
What effects does insulin have in the fat cells?
Glucose uptake
Lipogenesis
Less lipolysis
What effects does insulin have in the liver?
Glycogenesis
Lipogenesis
Less glycogenolysis
Less gluconeogenesis
What effects does insulin have in the pancreas?
β-cell growth
Less glucagon
Explain insulin signalling
Insulin binds to receptor, this dimerises, allowing it to self-phosphorylate
IRS-1 binds to the phosphorylated receptor
IRS-P -> PI3K-P -> PDK1-P -> AKT-P -> cytoskeletal arrangements allowing Glut4 to insert into cell membrane
How can hyperglycaemia occur from diabetes?
As insulin levels fall, so does β-cell mass and productivity
How can insulin promote candida?
Glucose in urine can damage tubules and the glucose-rich bladder promotes candida to grow
Explain the pathogenesis of insulin
Initial loss of response to insulin signalling
Glucose remains high, driving increased insulin production by β-cells.
β-cell mass and productivity fall
After insulin has fallen, blood glucose rises
How do glucose meters work?
Engineered glucose oxidase coupled to a test strip
What does glucagon do in the liver?
Coverts fatty acids to triglycerides
LDL and HDL increases in the blood
Circulating lipids are associated with increased atherosclerosis risk
What types of amylod form in type 2 diabetes?
Islet amyloid polypeptide (IAPP) produced by β-cells
What happens under insulin resistance?
Weight loss can reverse this in early stages
Akt signalling becomes refractory
Low level inflammation produced by visceral fat
