Cell Signaling & Metabolic Effects of Insulin & Glucagon PDF

Cell Signaling & Metabolic Effects of Insulin & Glucagon White blood cell chasing a bacteria https://www.youtube.com/watch?v=6q_QqE5E_To  Chemical Messengers Any substance in an organism Secreted from a cell in response to a specific stimulus travels to a tar...

Cell Signaling & Metabolic Effects of Insulin & Glucagon White blood cell chasing a bacteria https://www.youtube.com/watch?v=6q_QqE5E_To  Chemical Messengers Any substance in an organism Secreted from a cell in response to a specific stimulus travels to a target cell. Bind to specific receptor in target cell Elicit a response Function: Transmit messages between cells Cells can and do respond to multiple signals Figure 15-8 Molecular Biology of the Cell (© Garland Science 2008) How do Different Types of Cells Respond Differently to the Same Extracellular Signal Molecule? Figure 15-9b Molecular Biology of the Cell (© Garland Science 2008) Figure 15-9c Molecular Biology of the Cell (© Garland Science 2008) Figure 15-9d Molecular Biology of the Cell (© Garland Science 2008) Figure 15-9 Molecular Biology of the Cell (© Garland Science 2008)  Metabolic Effects of Insulin 1. Insulin is a peptide hormone 2. Produced by the  cells of the islets of Langerhans in the endocrine portion of the pancreas 2 inactive precursors cleaved to form active hormone and C-peptide Stored in cytosolic granules until stimulated to release by exocytosis Half-life in plasma Note: Species diversity – is approx 6 mins Role of pork and bovine insulin in the past Regulation of insulin secretion -coordinated with the release of glucagon Stimulated by a) Glucose b) Amino acids c) Gastrointestinal peptide hormones Inhibited by i. Conditions where there is a scarcity of dietary fuels ii. Periods of physiological stress  Metabolic Effects of Insulin 1.Promotes storage of nutrients as Glycogen, TAG Protein 2. Inhibits the mobilization of stored nutrients  Mechanism of Action of Insulin 1. Insulin receptor A tyrosine-kinase receptor 2. Signal Transduction Autophosphorylation initiates a cascade of cell-signaling responses. Dephosphorylation terminates the cascade 3. Membrane effects of insulin Promotes the movement of insulin-sensitive glucose transporters (GLUT-4) to the cell membrane (muscle and adipose tissue) 4. Receptor regulation H-R complex internalized and degraded 5. Time course of insulin actions Increased glucose uptake – secs changes in enzymatic activity –mins to hours changes in amount of the enzymes – hours to days  Insulin signalling - 4 mins https://www.youtube.com/watch?v=FkkK5lTm BYQ Insulin Signaling cascade and downstream events -10 mins https://www.youtube.com/watch?v=Dmnrz7yl H_o Please note: There are details in the videos which we have not covered in this module and are therefore not required learning The purpose of the animations is to give you a visual concept of the mechanics of signal transduction Glucagon A peptide hormone secreted by the  cells of the pancreatic islets of Langerhans Made as a single pp. Converted to active form by proteolytic cleavages Has a short half-life Along with epinephrine, norepinephrine, cortisol and growth home constitute the “counterregulatory” hormones i.e. oppose the actions of insulin Stimulation of Glucagon secretion 1. Low blood glucose 2. Amino acids 3. Catecholamines Inhibition of Glucagon Secretion A) Elevated blood glucose B) insulin  Metabolic Effects of Glucagon 1. Effects on CHO metabolism: IV Admin of glucagon leads to immediate rise in blood glucose from breakdown of liver glycogen Increase in hepatic gluconeogenesis 2. Effects on Lipid metabolism: Inhibition of FA synthesis by phosphorylation of Acetyl CoA carboxylase 3. Effects on Protein metabolism: Increases uptake by the liver of amino acids supplied by muscle, resulting in increased availability of C-skeletons for gluconeogenesis – plasma levels of aas are decreased Mechanism of Action of Glucagon Binds to high-affinity G protein-coupled receptor (GPCR) on the cell membrane of hepatocytes Activates adenylyl cyclase in the PM Leads to an increase in cAMP This activates cAMP-dependent protein kinase A This phosphorylates specific proteins Leads to phosphorylation-mediated activation or inhibition of key regulatory enzymes involved in CHO and lipid metabolism G protein signalling approx. 10 mins for both https://www.youtube.com/watch?v=wC2_7Ror3qY https://www.youtube.com/watch?v=EUE6liKCrPc cAMP 2nd messenger system https://www.youtube.com/watch?v=GskbODSxAU8 Which of the following statements about Insulin is correct? a) It has a half-life of approx. 60 mins b) Release is stimulated by glucose c) Release is stimulated by amino acids d) Release is stimulated during periods of physiological stress e) Works through a GPRC (G-protein coupled receptor) Which of the following statements about glucagon is correct? a) It is produced by the -cells of the islets of Langerhans b) Its release into the blood is stimulated by GI peptide hormones c) Transduces its signal through a tyrosine kinase receptor d) Leads to a rise in cAMP in target cells e) Likely to Induce the expression of hexokinase