E9

• Sources of energy


  • Carbohydrates
  • Lipids
  • Proteins- amino acids
• How energy is stored in the body


  • Glycogen
  • Triglycerides
• Carbohydrate metabolism


  1. Glycogenesis

  2. Glycogenolysis

  3. Gluconeogenesis
• Glycogenesis


  • The conversion of glucose to glycogen
  • Glycogen is the form in which glucose is stored if intake is higher than demand
  • Occurs in both the liver and muscle
  • Glycogen is stored within cytoplasmic granules
  • It can be quickly and easily broken back down into glucose molecules when needed – e.g. if blood glucose levels become too low
• Glycogenolysis


  Conversion of glycogen to glucose
• Gluconeogenesis


  • Synthesizing glucose from non-carbohydrate sources
  • Lactic acid, amino acids and glycerol can be converted into glucose
• Key players in fuel metabolism

  • Liver
  • Pancreas
  • Adipose tissue
  • Muscle
• Liver


  • Glucose uptake
  • Glycolysis
  • Gluconeogenesis
  • Glycogen storage and release
  • De novo lipogenesis
  • Fatty acid oxidation
• Pancreas


  • Insulin secretion
  • Glucagon secretion
• Adipose tissue


  • Glucose uptake
  • Triglyceride storage
  • Fatty acid release
• Muscle


  • Glucose uptake
  • Glycogen storage
  • Triglyceride
• Carbohydrate is the body's primary energy source in cell metabolism. It is the brains only source of fuel
• Need for effective and efficient means of metabolising carbohydrate and transporting it into cells
• Carbohydrates are broken down into glucose for use by the cells
• Following its absorption from the intestine (jejunum and ileum), glucose remains in the blood until it is taken up into cells
• Blood levels of glucose must be kept within strict limits
• Even if we eat more carbohydrate than the body needs for fuel, it must be removed from the blood and stored elsewhere
• Normal blood glucose levels


  • Between meals ~ 4-6mmol/L
  • After meals ~ 10mmol/L
• Hyperglycaemia


  • Too high blood glucose
  • Symptoms: None, Polyuria, Thirst, Weight loss, Fatigue
  • Consequences: Neuropathy, nephropathy, Heart disease, Cataracts and blindness, Diabetic coma, Death
• Hypoglycaemia


  • Too low blood glucose
  • Symptoms: Irritability, fatigue, Food cravings, Headaches, Dizziness, Shaking, Confusion
  • Consequences: Loss of consciousness, Accidents and injury, Weight gain, Reduced IQ, Brain abnormalities
• Islets of Langerhans


  • Alpha cells (25%)- glucagon
  • Beta cells (70%)- insulin
  • Delta cells (5%)- somatostatin
• Insulin


  • Polypeptide
  • Processed from pre-proinsulin to form insulin and c-peptide
  • Allows circulating glucose to be used by cells
• Glucose sensing and insulin secretion


  1. Glucose uptake by GLUT2

  2. Glucokinase becomes activated when glucose levels increase- it catalyses the phosphorylation of glucose to glucose-6-phosphate

  3. ATP sensitive potassium channel- blocks K from leaving when ATP high

  4. K ions cannot efflux- causes depolarisation

  5. Voltage-gated calcium channels allow Ca entry

  6. Insulin release via vesicles- exocytosis
• Insulin effects on muscle


  • Promotes glucose entering muscle by GLUT4 and conversion to glycogen in minutes
  • Increases expression and translocation of lipoprotein lipase (LPL) – in 2-3hours
• Insulin


  • Secreted by beta cells of pancreatic islets
  • Promotes formation of glycogen
  • Inhibits gluconeogenesis
  • Enhances movement of glucose into adipose and muscle cells
  • Decreases blood glucose concentrations
  • Promotes transport of amino acids
  • Enhances synthesis of proteins and fats
  • Controlled by blood glucose concentrations
• Glucagon


  • Has an antagonistic action of insulin
  • Secreted by alpha cells of the islets of Langerhans
  • Secreted in response to LOW blood sugar
• Glucagon synthesis


  1. Pro-glucagon undergoes proteolytic processing in alpha cells

  2. GRPP, glucagon, major proglucagon fragment
• Glucagon action within the cell


  1. When glucose low in blood

  2. Glucagon enters receptor of liver cell

  3. ATP, cAMP- make and activate protein kinase A

  4. Glycolysis – produces glucose

  5. Glycogen turns into glucose
• Glucagon actions


  • Promotes gluconeogenesis
  • Promotes glycogenolysis
  • Glucagon increases ketogenesis and lipolysis
  • The formation of ketone bodies (from fatty acid oxidation)
  • Ketogenesis occurs in the liver, and lipolysis in the adipose tissues, from an initial substrate of: long chain fatty acids, amino acids; such as leucine and lysine
  • Inhibits lipogenesis
• Insulin


  INCREASES: Glycogenesis, Lipogenesis

  DECREASES: Glycogenolysis, Gluconeogenesis, Ketogenesis, Lipolysis
• Glucagon


  Has the opposite effect of insulin
• Counter-regulatory actions of insulin and glucagon

  Drop in blood glucose: Alpha cells detect a drop, Alpha cells secrete glucagon, Glucagon stimulates cells to break down glycogen into glucose and stimulates cells to convert non-carbs into glucose, Blood glucose rises towards normal and inhibits glucagon secretion

  Rise in blood glucose: Beta cells detect a rise in blood glucose, Beta cells secrete insulin, Insulin promotes movement of glucose into certain cells, Insulin stimulates formation of glycogen form glucose, Blood glucose drops towards normal and inhibits insulin secretion
• Other hormones involved in glucose homeostasis


  • Growth hormone
  • Epinephrine (adrenalin)
  • Glucocorticoids
  • Somatostatin
  • Glucagon-like peptide -1 (GLP-1)
• Glucagon-like peptide 1


  • Produced by proteolytic processing of proglucagon in intestinal cells
  • Dipeptidyl peptidase IV prevents this
• Analogues of GLP-1


  • Exendin-4 (exenatide): Related structure to GLP-1, Resists DPP IV degradation, Sc injection

  Liraglutide: Albumin binding, Decreased degradation by DPP IV, Sc injection
• Sodium-Glucose co-transporters 2 (SGLT2) inhibitors


  SGLT2- in kidney- proximal renal tubule

  In hyperglycaemia- high filtered load of glucose- filtered load exceeds reabsorption capacity