How does obesity & Lipodystrophy cause insulin resistance ?
it cause severe defects in lipid and glucose homeostasis as the balance between them is thrown off and you’re peripheral insuin resistance and T2D prone
what is the link between obesity & insulin resistance and what does it affect ?
with excess adipose tissue it leads to more fatty acid circulation as it is unable to store which leads to more Insulin resistance in the muscle and liver
what is the positive net energy balance effect in the body for TG?
- with increase calorie intake and decreased energy expenditure there is a positive net energy balance
- TG (triglyceride) accumulation is occurring in non adipose tissue as the adipocytes cannot store it
- increase lipolysis along with insulin resistance
- fatty acid spillover from adipose to non adipose tissue overall leads to an insulin resistance state and T2D
with fatty acid spillover what is the effect on the muscle, liver & pancreas
in muscle impaired glucose metabolism
in liver bad cholesterol production and bad insulin clearance
in pancreas Beta cell damage
why is fatty acid oxidation rates higher in endurance athletes
the oxidation rate is higher due increased mitochondrial activity and prevention of TAG associating with DAG &B Cerimindes
what is subcutaneous fat ?
its good fat to keep you warm
what is ectopic fat?
bad visceral fat that leads to T2D
what is the difference between femoral, abdominal & visceral fat tissue growth?
femoral is subcutaneous fat that has increased adipogenesis and replication
abdominal is subcutaneous fat with middle level adipogenesis and replication
Visceral is visceral fat with less adipogenesis and replication and bigger cells
when and who discovered insulin ?
Dr Frederick banting and Charles Best discovered insulin which can treat type I Diabetes in 1921
when and who discovered the difference insulin secretion & insulin sensitivity ?
in 1936 harry himsworth differentiated them
what is substance X ?
fatty acids which connects obesity to insulin resistance and causes it
what is adiponectin
an adipokine that adipose tissue produce to deal with decreasing obesity
what is lipodystrophy ?
it is partial and complete lost of adipose tissue
what 2 things lead to fatty acids ?
lipodystrophy and excess adipose tissue
what is the normal insulin signaling and regulation of glucose & lipid homeostasis pathway ?
- insulin inhibits the liver from performing gluconeogenesis/glycogenolysis that produces glucose whilst fatty acids promotes it
- Insulin also prevents lipolysis from occurring which prevent more FFA
- FFA, TNF A and resistin inhibits insulin dependent glucose uptake in the muscle and fat whilst adiponectin promotes it
how does insulin help make TG and prevent Fatty Acid conversion
Insulin stimulates 2 pathways the first one being FFA entering the cell and converting to FA with the help of lipoprotein and insulin and become FACoA which become DAG and get converted to TG to be stored. the second pathway is insulin helping glucose get into the cell and glucose become Glycerol 3P which converts to DAG and then TG . insulin prevents TG being converted into FA by inhibiting HSL
what are the 2 ways glucose is able to get into the cell
by contraction and insulin which release GLUT 4
what is the benefit insulin and exercise (contraction) working together than by itself
with contraction and insulin working together increase more glucose transportation than alone
what can insulin and exercise activate and what cannot be activated on their own
insulin can activate PI3K & IRS but not exercise
Exercise stimulates AMPK but not insulin
what is the affect of Wortmannin on AICAR, Contraction & Insulin?
wort only inhibits insulin for glucose transportation
Amongst AICAR, Contraction & Insulin which joint group has no additive affect on muscle glucose uptake ?
AICAR + Contraction has no affect everyone needs insulin for an additive effect on glucose uptake
what is the GLUT 4 translocation Insulin signalling pathway
- insulin binds to the insulin receptor (IR)
- Phosphorylation of of IRS 1
- p85 binds to p13K and PI3K is activated
- increase in PIP3 leads to activation of PDK1
- AKT is phosphorylated 2x and PDK1 activates aPKC
- PKC + AKT inhibits RAB by phosphorylating AS160
what is the GLUT 4 translocation contraction signalling pathway
contraction directly phosphorylates akt and aPKC and AMPK to inhibit RAB
what are the 4 ways to increase GLUT4 translocation ?
- AMPK
- AICAR
- Contraction
- Insulin
