Block 3 Lecture 34 Flashcards
what is the first impairment site in insulin resistance
vascular delivery of glucose and insulin to the skeletal muscle tissue
what affect does insulin have on vasculature
it has a net vasodilator action by causing relaxation of smooth muscle in blood cells
what happens in the metabolic syndrome when the action of insulin to induce capillary vasodilation is impaired
it reduces the transendothexila transport of glucose and insulin into extracellular space of the skeletal muscle
what affects does tyrosine phosphorylation have on the insulin receptor and IRS-1
it is a positive modulator of signaling events
what affects does serine phosphorylation have on the insulin receptor and IRS-1
it is a negative modulator of signaling events by decreasing the tyrosine kinase activity of this protein by altering its 3D conformation
what happens when the 3D conformation of tyrosine kinase is altered due to serine phosphorylation
it impairs 3D conformation of IRS-1, its ability to act as a docking protein with other signaling elements such as PI3K
what type of kinase is PKC
serine kinase
what is PKC regulated by
DAG and Ca2+
how can PKCtheta be positively regulated by FFAs
when there is an increase in the delivery of FFAs to the myocyte, PKC isoforms can be activated which then act on the insulin receptor and IRS-1 to increase serine phosphorylation and decrease their functionality
what happens to PKC is dyslipidemic states
elevations in plasma FFAs can induce overactivity of PKC making insulin resistance worse by phosphorylating serine
what happens in stress activated serine kinase
serine kinases in skeletal muscle cells are activated by interventions that increase cellular stress such as the production of inflammatory factors or oxidative stress factors
what are some inflammatory factors that activate stress activated serine kinases
CRP and IL6
what increases the production of ROS and H2O2
hyperglycemia and dyslipidemia
what serine kinases do ROS and H2O2 activate in the myocyte
IKK-beta, MAP kinases, JNK, p38 MAPK, and GSK-3Beta
what do the serine kinases activated by ROS and H2O2 do
they phosphorylate serine residues on IRS-1
