Muscles and insulin Flashcards
Describe insulin
It is a peptide hormone with 51 amino acids. It has two chains (A and B) that are linked together by disulfide bonds. It is synthesized in the pancreas by beta cells in the form of preproinsulin, then is secreted as mature insulin
Describe the structure of preproinsulin
Full protein with no disulfide bonds and has a signal sequence that indicates where insulin is within the cell.
Describe the structure of Proinsulin
The signal sequence is removed and disulfide bonds are made between two parts of the polypeptide ‘loops’
Describe the structure of mature insulin
Protease cleaves part of the peptide (c peptide) from the chain, leaving insulin.
Describe how the insulin receptor works
These receptors are found in the cell membrane and will bind insulin as a dimer with high affinity. The signal is then transferred into the membrane to tyrosine kinases that are the inner part of this receptor.
The tyrosine kinases will phosphorylate each other, which can then phosphorylate the target protein(Insulin receptor substrate-1).
Describe the insulin signaling pathway
Insulin will bind the receptor as a dimer, which will then phosphorylate Insulin receptor substrate-1, allowing it to then phosphorylate Grb2 (Regulator that turns on the MAPkinase pathway, which turns on protein synthesis of GLUT4). IRS1 will also bind PI-3k, which turns phosphorylated lipid PIP2 to PIP3, which in turn signals for GLUT4 proteins from within the cells to be moved to the surface of the cell, increasing the cells ability to uptake glucose.
What target pathways does the insulin signal pathway “turn on”
1) GLUT4 to the membrane (Muscle and adipose)
2) Glycogen synthesis (Liver and muscle)
3) Glycolysis (Liver)
4) Fatty acid synthesis (Liver)
5) Amino acid uptake and protein synthesis (Muscle)
What target pathways does the insulin signal pathway “turn off”
1) TAG breakdown (Adipose)
2) Gluconeogenesis (Liver)
3) Glycogen breakdown (Liver)
Describe the GLUT4 to the membrane target pathway
GLUT4 has 12 transmembrane helicies arranged to create an open/close pore for glucose to enter the cell through. It has a [glucose] km=5mM as this is resting blood glucose levels. PIP3 will activate protein kinase B which will stimulate the movement of GLUT4 transporters from vesicles within the cell to the cell surface, allowing glucose to be more effectively drawn into the cell.
Describe the Glycogen synthesis target pathway
PIP3 activating protein kinase B will phosphorylate glycogen synthase kinase 3, which will inactivate it, relieving inhibition on glycogen synthase and activating it.
Describe the Glycogen breakdown target pathway
Insulin receptor will activate protein phosphatase, which cleaves phosphate off glycogen phosphorylase, inactivating it. This prevents the breakdown of glycogen into glucose.
