Block 3Lecture 33 Flashcards
(31 cards)
what are the 2 critical stages of regulation for glucose by skeletal muscle
- vascular delivery of blood glucose
2. transmembrane transport of glucose
what is glucose metabolism based on
energetic needs and endocrine status
how does skeletal muscle receive blood
via systemic circulation
how the tissue receives blood depends on what?
- cardiac output
- vascular resistance
- capillary density
what is vascular resistance
degree of vasodilation in vascular bed supplying tissue
what is capillary density
number of capillary contacts to the skeletal muscle
what happens in insulin mediated dilation
insulin acts on endothelial cells in arteries to activate eNOS causing synthesis of NO which causes relaxation of cells and vasodilation to promote glucose delivery to skeletal muscle
what mechanisms does insulin mediated dilation use
increased capillary recruitment and greater capillary surface area
where are insulin receptors located in myocytes
in the sarcolemmal membrane
what is the main glucose transporter under insulin-mediated conditions
GLUT4
what type of receptor is the insulin receptor
a receptor tyrosine kinase, a major type of catalytic receptor
describe the structure of the insulin receptor
- it is a heterotetramer
- consists of 2 extracellular a-subunits that bind the hormone
- and 2 transmembrane beta subunits that have tyrosine kinase domains on the cytosolic side
what are the a and beta subunits joined by in the insulin receptor
sulfhydryl bonds
where does insulin bind on the insulin receptor
the cysteine rich domains of the a subunits thereby enhancing tyrosine kinase activity of the beta subunits
What is a primary substrate for activated insulin receptor tyrosine kinase
insulin receptor substance (IRS)
what are the major isoforms of IRS in skeletal muscle
IRS1 and IRS2
what are the effects of activated insulin receptor and IRS
stimulation of glucose transport, enhances glucose storage as glycogen, increased protein synthesis, decreased protein breakdown, unregulation of lipid synthesis, and alterations in the expression of genes in the nucleus
what is IRS1 and what can it do when phosphorylated
it is a docking protein, that can interact with effector proteins that possess SH2 domains
what can PI3K interact with
dock with tyrosine phosphorylated IRS1 and SH2 domains
what does PI3K do
produces signals that causes intracellular vesicles containing GLUT4 to fuse into sarcolemmal membrane
explain the IRS-1/PI3K/AKt pathway in full
insulin binds to insulin receptor which signals IRS-1 to get phosphorylated, then it binds to effector proteins with SH2 domains, then PI3K can interact with this complex, the activation of this leads to fusion of vesicles containing GLUT4 to fuse into the membrane so the myocyte can transport glucose through facilitated diffusion
what happens when the insulin disengages from the insulin receptor
tyrosine phosphatase dephosphorylate tyrosine residues on IRS-1
what is the location and Km for GLUT1
location- almost all tissues
Km- about 3mM
what is the location and Km for GLUT2
location- basolateral membrane of liver, pancreatic beta cells (in rodents not humans), intestine and kidney
Km- 17mM
