• Explain hormonal regulation of metabolic processes. (EOC 1.A, Level 1) The 4 major tissues play a role in fuel metabolism. Those are the liver, adipose tissue, muscles, and the brain. Insulin, glucagon, and catecholamines (E/NE) are important for fuel metabolism. The hormones can be carried by the bloodsteam to nearby cells or another organ. Insulin and glucagon are produced in the islet of Langerhans of the pancreas. Compare and contrast the roles of insulin and glucagon during the fed, basal, and starvation states. (EOC 1.A, Level 1) Insulin “ I just ate” – secreted in response to increased blood glucose levels, promotes the storage of glucose, fat, and amino acids; stimulates the synthesis of macromolecule breakdown • The actions of insulin and glucagon are opposing. High blood glucose – insulin released – fat cells take in glucose – normal glucose level Low blood glucose – glucagon – liver releases glucose to blood – normal glucose level Fed State : Insulin dominates - increase of glycogen synthesis, fat synthesis, protein synthesis, glucose oxidation Insulin : Glucagon Ratio Liver – High ; increases glucose uptake and glycolysis, increased glycogen synthesis, increased fatty acid synthesis inhibits gluconeogenesis, glycogenolysis, ketogenesis, lipolysis some G6P is used in the PPP to make NADPH , excess glucose and amino acids are catabolized to acetyl coA Muscle – High ; increase uptake of glucose by GLUT4, inhibits protein degradation Muscles lack fatty acid synthase and G6Phophatase, excess G6P is used to replenish glycogen stores Adipose Tissue – Hight fuel needs for the brain are large and easily met during fed state; depends on glucose as the main fuel during this state and enters through GLUT1 that is insulin dependent the brain has no storage for glycogen or tag to be used for energy and fatty acids cannot cross the blood brain barrier 2hrs post prandial , the blood glucose begins to drop this causes glucagon to be secreted to switch from being anabolic to catabolic process ; gluconeogenesis is stimulated and glycogenolysis is increased 4hrs postprandial more glucagon is released, more TAG is hydrolyzed and FA become fuel for the muscle and liver Fasted State : Glucagon dominates – increase glycogenolysis, gluconeogenesis, ketogenesis Insulin Glucagon Ratio Low Liver - increases glycogenolysis , TAG breakdown, glycogen phosphorylase, gluconeogenesis inhibits glycogen synthase Muscle – responds to Epinephrine; muscle cells lack glucagon receptors cell get energy from Boxidation of fatty acids from blood increased acetyl CoA inhibits glycolysis lactate is released from the muscle and sent to the liver by gluconeogenesis, glycogen stores are rapidly depleted Adipose Tissue – glycerol is sent to the liver for gluconeogenesis , fatty acids are released to the liver to under Boxidation to produce acetyl CoA needed for ketone bodies HS lipase is activated to breakdown TAG Brain – glucose is provided from the liver; ketone bodies can also be used as an alternative source for fuel • Predict how alterations in metabolic processes can lead to disease. Elevated levels of glycosylated proteins increase the risk of cardiovascular disease, renal failure, and damage to small blood vessels and nerves. High blood glucose levels is a warning sign for diabetes. Low fasting glucose levels are warning signs for hypoglycemic conditions. • Compare and contrast the role of insulin and glucagon in the liver, muscle, adipose tissue, and the brain. Identify which hormone is predominant in fed, fasted, and starved state. Insulin is predominant in the fed state, Glucagon is predominant in the fasted state Describe the role of glucose transporters and identify which GLUT are insulin dependent. Glucose is taken into the cells and phosphorylated to trap it inside of the cells. GLUT1 – brain, muscle, placenta, adipose tissue GLUT2 – pancreatic b cells, liver, small intestine, renal proximal tubule GLUT3 – neural small intestine GLUT4 – muscle heart, adipose tissue insulin dependent • • • Describe the metabolic alterations that occur in T1D and T2D. Type I – fat breakdown is accelerated which leads to a high production of ketone bodies. Some ketone bodies are acids which can lead to ketoacidosis. Untreated diabetes leads to a dramatic weight loss. No insulin is produced Glucagon has an unopposed action Type II – 27% of population, high levels of free fatty acids, resistant to insulin hyperglycemia increases glucose uptake