Week 5

• Glucose homeostasis


  Glucose homeostasis in the body is primarily controlled by the two metabolic hormones produced by the pancreas: insulin and glucagon
• The pancreas


  • Small, leaf-like gland in the retroperitoneum, posterior to the stomach
  • Has both exocrine and endocrine functions
• Exocrine functions of the pancreas

  Acinar cells arranged in lobules that secrete a range of digestive enzymes, sodium bicarbonate and other electrolytes into the duodenum of the small intestines
• Endocrine functions of the pancreas


  Islets of Langerhans secrete hormones into systemic blood
• Major types of endocrine cells in the Islets of Langerhans

  • Beta cells
  • Alpha cells
  • Delta cells
• Beta cells


  Produce insulin
• Insulin


  Anabolic, promotes the storage of glucose, fatty acids and amino acids in cells
• Alpha cells


  Produce glucagon
• Glucagon


  Catabolic, mobilises glucose, fatty acids and amino acids for energy production
• Delta cells


  Produce somatostatin
• Somatostatin


  Acts locally within the pancreas to inhibit both insulin and glucagon secretion
• Insulin and glucagon


  Functional antagonists, act opposite to each other and are reciprocally secreted in most circumstances
• Impaired insulin secretion or insulin action results in the metabolic disease called diabetes mellitus
• Insulin is the only blood glucose lowering hormone in the body, which explains why diabetes mellitus is such a significant global disease
• Diabetes mellitus is a metabolic disease involving carbohydrate, lipid, and protein metabolism
• People often use the single term 'diabetes' in relation to diabetes mellitus and glucose homeostasis
• There is also diabetes insipidus, which is less common and related to endocrine dysfunction associated with anti-diuretic hormone
• A lack of glucagon secretion and/or action can be compensated for by other hormones, and no disease state exists for glucagon insufficiency
• Excess glucagon production occurs in glucagonoma, a tumour of the pancreatic alpha cells that hyper-secretes glucagon
• A person with elevated blood glucose levels will likely exhibit increased secretion of insulin from their pancreatic beta cells within the Islet of Langerhans
• Insulin is the only blood glucose lowering hormone in the body
• Key target tissues of insulin

  • Liver (hepatocytes)
  • Muscle (both skeletal and cardiac muscle)
  • Fat (adipose cells)
• Insulin does not promote glucose uptake into neurons in the central nervous system
• Carrier mediated diffusion


  Molecules are transported "down" a concentration gradient, and therefore this process does not require energy
• Active transport


  Molecules are transported "uphill" against the concentration gradient and requires energy (ATP)
• The presence of a transporter increases the rate of transport across the cell membrane compared to diffusion alone
• Glucose transporters


  Membrane proteins that facilitate the transport of large glucose molecules across the membrane
• Glucose transporters do not require energy to perform such transport
• Carrier-mediated transport


  Exhibits the properties of specificity, competition, and saturation
• Glucose is the most important and potent stimulator of insulin secretion from the pancreatic beta cells


  Other regulators include other nutrients, the autonomic nervous system, other endocrine signals from the gastrointestinal tract, and paracrine signals within the pancreas
• Steps leading to the release of insulin from pancreatic beta cells

  1. Glucose enters the pancreatic beta cell via GLUT2 transporters

  2. Glucose is metabolised into ATP inside the beta cell

  3. ATP causes the closure of K+ channels, resulting in a building up of K+ inside the beta cell

  4. Ca2+ voltage gated ion channels open, resulting in an influx of a Ca2+ ions

  5. Insulin containing vesicles are transported to the cell membrane, where they release insulin via exocytosis
• Incretins


  Hormones produced by the gastrointestinal tract in response to nutrients that influence insulin's response to glucose
• Parasympathetic nervous system


  Releases acetylcholine that stimulates insulin secretion
• Sympathetic nervous system


  Releases noradrenaline that inhibits insulin secretion
• Glycogenesis


  Formation of glycogen
• Glycogenolysis


  Breakdown of glycogen
• Glycolysis


  Breakdown of glucose, releasing energy and producing pyruvate
• Lipogenesis


  Formation of fat
• Lipolysis


  Breakdown of fat
• The liver is a key metabolic organ