BIOL 2420 Lecture Notes - Lecture 7: Insulin Receptor, Adipose Tissue, Glut4
26 Apr 2018
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Unit 10 – Lecture 7
Insulin Promotes Anabolism
- Insulin
o Peptide hormone
o Combines with a membrane receptor on its target cells
o Insulin receptor has tyrosine kinase activity – initiates complex intracellular cascades
whose details are still not completely understood
▪ Activated insulin receptor phosphorylates proteins that include a group known
as the insulin-receptor substrates (RS)
▪ Proteins act through complicated pathways to influence transport and cellular
metabolism
o Enzymes that regulate metabolic pathways may be inhibited or activated directly or
their synthesis may be influenced indirectly through transcription factors
- primary target tissues for insulin are the liver, adipose tissue and skeletal muscles
o usual target cell response is increased glucose metabolism
- in some target tissues, insulin also regulates the GLUT transporters
- other tissues
o brain
o transporting epithelia of the kidney and intestine
o are insulin-independent
▪ do not require insulin for glucose uptake and metabolism
- insulin lowers plasma glucose in 4 ways
1. insulin increases glucose transport into most but not all insulin-sensitive cells
o adipose tissue and resting skeletal muscle require insulin for glucose uptake
o without insulin, their GLUT4 transporters are withdrawn from the membrane and stored
in cytoplasmic vesicles
▪ example of membrane recycling
o insulin binds to the receptor and activates it
▪ resulting signal transduction cascade causes the vesicles to move to the cell
membrane and insert the GLUT4 transporters by exocytosis
▪ followed by cells taking up glucose from the interstitial fluid by facilitated
diffusion
o exercising skeletal muscle is not dependent on insulin activity for its glucose uptake
▪ when muscles contract, GLUT4 transporters are inserted into the membrane
even in the absence of insulin and glucose uptake increases
o intracellular signal for this is complex but appears to involve Ca2+ as well as a variety of
intracellular proteins
o glucose transport in liver cells (hepatocytes) is not directly insulin dependent but is
influenced by the presence or absence of insulin
▪ liver cells have GLUT2 transporters always present in the cell membrane
▪ fasted-state
• when insulin levels are low, glucose moves out of the liver and into the
blood to help maintain glucose homeostasis
o liver cells are converting glycogen stores and amino acids to
glucose
o newly formed glucose moves down its concentration gradient
out of the cell using GLUT2 facilitated diffusion transporters
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