Study guide for Exam 2 HNF 461 1 How is glucose absorbed in the small intestine With high glucose in the intestinal lumen which pathway is dominant Glucose alone cannot cross cell membranes it needs a carrier GLUT1 RBCs GLUT2 liver pancreatic B cells small intestine GLUT3 neurons GLUT4 muscle and adipose tissue 3 ways of glucose absorption in the small intestine sodium glucose cotransporter secondary active transport When glucose and fructose in lumen is high GLUT2 facilitated diffusion Fructose GLUT 5 o To go out of the small intestine glucose fructose GLUT2 2 How does insulin regulate intestinal glucose absorption Through which transporter When insulin is released GLUT2 is inhibited you already have enough glucose so you do not need to take in more Note Insulin binds to receptors on muscle and adipose tissue only With glucose injection you have less insulin produced because you are bypassing absorption thus more glucose is absorbed through GLUT2 due to the lack of inhibition 3 Understand the concept and the meaning of Km How do the Kms of GLUT1 2 and 4 compare to each other What s the physicological importance of that The the Km the the affinity The the Km the the affinity Glut 1 and 3 responsible for basal uptake in many tissues have a very low km higher affinity Glut 2 in the liver enterocytes and pancreatic B cells has a very high Km lower affinity Glut 3 in the brain has a very low Km high affinity Glut 4 in muscles and adipose tissue has a physiological Km regulated by insulin 4 Does the liver absorb dietary glucose fructose and galactose from the portal vein differently Liver is the first organ after intestinal absorption except for fats Fructose and galactose are removed by the liver o If too much fructose galactose is consumed the liver cannot process it all and it turns them into fat Some glucose is removed by the liver but GLUT2 has a high Km low affinity Increase in blood glucose leads to insulin secretion 5 What tissues have GLUT4 How is GLUT 4 regulated By making new GLUT4 or by regulating its location in the cells GLUT 4 is present in muscle and adipose tissue This transporter has a physiological Km GLUT 4 is regulated by insulin insulin triggers translocation of GLUT4 from the vessels in the cell to the membrane 6 What is diabetes What is the difference between type I and type II Diabetes Impaired fasting glucose Impaired glucose tolerance Lots of glucose in the blood Type I diabetes An autoimmune disease that destroys pancreatic B cells This causes a lack of insulin secretion The actions of glucagon and glucorticoids are not inhibited The body keeps making glucose because it cannot absorb any from the blood This leads to hyperglycemia ketoacidosis urination and electrolyte imbalance Type II diabetes tissues and organs are not responsive to insulin Genetic predisposition coupled with environmental factors Starts with insulin resistance in the muscle which slows uptake via GLUT4 Increase in insulin secretion but no glucose uptake Liver and adipocytes ARE RESPONSIVE so adipocytes take in glucose and convert in to fat 7 Know the conversion of glucose between mM and mg dL 5mM 90 mg dL Remember the numbers unless you really know how to calculate them 10mM glucose 180 mg dl 5 mM glucose 90mg dl 8 Know how diabetes and prediabetes are defined based on the results of oral glucose tolerance test Diagnosis of diabetes impaired fasting glucose 126 mg dl or Impaired glucose tolerance if plasma glucose is 200 mg dl or at 2 hours Prediabetes Fasting plasma glucose between 100mg dl and 125 mg dl Plasma glucose 2h post glucose consumption between 140mg dl and 199 mg dl 9 What does HBA1C measure Is it an indicator of a long term or short term glucose level Why HBA1C measures glycated hemoglobin This does not require fasting since it is based on free glucose in the blood This is an indicator of long term glucose level 10 Is there an association between type II diabetes and obesity Yes because the muscle is not responsive to insulin the body keeps making insulin in hopes of increasing glucose absorption in the muscle However the liver and adipocytes are responsive to insulin so the adipocytes increase lipid storage convert it to fat Prolonged increase in blood insulin leads to resistance in the liver This makes it harder to control gluconeogenesis as insulin cannot inhibit this process You get further increase in blood glucose and more insulin secretion This leads to more obesity adipocytes are still responsive to insulin and store fat 11 Describe the etiology of type II diabetes In other words insulin resistance in what tissues leads to type II diabetes Insulin resistance in muscle leads to type II diabetes Eventually liver is resistant too Adipocytes are not resistant they are stimulated by insulin and take in glucose and make fats 12 What are the a few key things to do to prevent or delay the onset type II diabetes The key is to prevent limit muscle resistance Prevent onset of obesity Exercise makes muscles more responsive to insulin Consume complex carbohydrates legumes whole grains Low glycemic index foods with ample dietary fiber 13 What are the two systems that metabolize alcohol in the liver Alcohol metabolism in the liver o Ethanol NAD acetylaldehyde NADH o Acetylaldehyde NAD acetate NADH o Acetate CoA Acetyl CoA o 2 NADH produced 1 acetyl CoA formed Microsomal ethanol oxidizing system MEOS o Occurs in microsomes o Active when high alcohol intake o Yields H2O rather than NADH 14 How does alcohol alter the NADH NAD ratio in the liver What is the adverse consequence of that The metabolism of alcohol increases the NADH NAD ratio since more NADH is produced The high NADH ratio prevents the conversion of lactate to pyruvate which forms NADH thus gluconeogenesis is inhibited hypoglycemia occurs 15 Where is the hormone sensitive lipase In what tissue Inside or outside of cells What does this enzyme do How is it regulated The hormone sensitive lipase is located in adipose tissue It hydrolyses triglycerides to yield nonesterified fatty acids NEFA Hormone sensitive lipase is activated by glucagon and epinephrine and inhibited by insulin acting on their respective cell membrane receptors Nonesterified fatty acids NEFA are carried by albumin in the blood to tissues for oxidation 16 What does NEFA bind to in the blood for transport Nonesterified fatty acids bind to albumin in the blood and are carried to tissues for oxidation B oxidation 17 What macronutrient does resting muscle use