Signal Transduction 4: Insulin Flashcards
What are the hormones produced where, target tissue and receptor type of the two hormones produced when Blood glucose is low
Two hormones:
Epinephrine (fofr) from Adrenal medulla targets muscle and liver
Glucagon (fasting) from Pancreatic alpha cells target mainly liver
Both use GPCR receptors
What is the hormone produced where, target tissue and receptor type of the hormone produced when Blood glucose is high
Insulin produced by pancreatic beta cells acts on muscle and liver cells
This is receptor tyrosine kinase
Describe the signal transduction pathway of Glucagon and Epinephrine : incl 2nd messenger
- Hormone binds to GPCR activating G cycle
- a-subunit binds to Adenylate cyclase (AC)
- AC makes cAMP (2nd messenger)
- cAMP activates protein kinase A
- Protein kinase A phosphorylates PHosphorylase kinase and inactivates glycogen synthase (by phosphorylation)
- Phosphorylase kinase activates Glycogen phosphorylase which breaks down glycogen into glucose 1 phosphate
What is the response induced by glucagon in the target tissue
Glycogen breakdown & Gluconeogenesis promoted
However Glycolysis is decreased in the liver so that it can send glucose out in the blood for others
What is the response induced by epinephrine in the target tissue
In muscles: Increase of Glycogen breakdown and glycolysis to use it. Epinephrine also supports response of glucagon in liver
How is Glycogen degradation regulated (turned off)
- The hormones that stimulate glycogen breakdown are no longer present.
- The inherent GTPase activity of Ga subunit inactivates G protein signalling (hydrolysis of GTP)
- 2nd messenger cAMP removed by phosphodiesterase making AMP
- Phosphatases remove phosphates from phosphorylase kinase and glycogen phosphorylase inactivating enzyme.
What is the speed of response from glucagon in the liver
Glucagon has rapid increase in glucose in liver within 5 minutes.
Describe the insulin receptor
It is a Receptor Tyrosine kinase.
- Monomer: Extracellular a-subunit bound to intracellular B-subunit containing the kinase enzyme by disulphide bond.
- Each monomer has 1 transmembrane alpha helix
- Must be dimer to work
Describe the transduction pathway for Insulin : 2nd messenger is what?
- Insulin binds, causing the extracellular portion of two monomers of receptors to come close together.
- This makes the intracellular portion come close together.
- When the tyrosine kinase close enough, they can phosphorylate each other
- This makes the B subunit of the tyrosine kinase catalytically active therefore able to phosphorylate downstream molecules in cascade
- This leads to the insertion of glucose transporters GLUT4 into the cell membrane.
What is the response of insulin in the target tissues
Muscle cell: increase glucose uptake in muscle cells–> reduce blood glucose
Liver: promotes storage of glucose as glycogen
What are the two ways that the level of opposing hormones are controlled
- An increase/decrease in blood glucose levels triggers production of hormone
- There is paracrine effect between islet cells in pancreas which inhibit the opposing hormone directly
Name associated disease with defect in signal
Insulin deficiency- type 1 diabetes where signalling molecule is absent
Name associated disease with defect in reception
Mutation in Melanocortin 4 receptors that makes it dysfunctional
Name associated disease with defect in transduction
Cholera: where cholera toxin locks G-as protein into its active form. Therefore leading to increased activation of adenylate cyclase-> cAMP-> protein kinase A.
In the intestinal cells this leads to phosphorylation of ion channels so that it excretes chloride ions. A as a result, large amounts of water is excreted causing diarrhoea
