pancreas and diabetes

• Endocrine pancreas


  Comprised of islets of Langerhans (<2% of the total cellular mass) – comprised primarily of a, b and d cells - secrete insulin and glucagon into blood

  
• Exocrine pancreas


  Comprised of acini - secrete digestive enzymes and bicarbonate into duodenum

  
• Cells in islets of Langerhans


  • Alpha a cell (Glucagon)
  • Beta b cell (Insulin)
  • Delta d cell (Somatostatin)

  
• Absorptive (fed) and post-absorptive (fasted) states


  1. Brain must be continuously supplied with glucose (no carbohydrate storage)

  2. After a meal, nutrients are ingested and are entering the blood - causing high glucose levels

  3. Food intake is intermittent, therefore nutrients must be stored

  4. In post-absorptive (fasted) state, stored substrates are degraded to release utilizable units (glucose, fatty acids, amino acids, etc)

  
• High plasma glucose


  Insulin secretion stimulated
• Low plasma glucose


  Insulin secretion inhibited
• High free fatty acids, amino acids


  Insulin secretion stimulated

  
• Sympathetic stimulation / adrenaline


  Insulin secretion inhibited
• Parasympathetic stimulation


  Insulin secretion stimulated
• Gastrointestinal hormones (e.g. Glucose-dependent insulinotropic peptide (GIP) & glucagon-like peptide (GLP1))


  Insulin secretion stimulated

  
• Somatostatin


  Insulin secretion inhibited
• Regulation of insulin secretion


  Insulin receptor signalling pathways: 1. Translocation of proteins into cell membranes (within seconds), 2. Phosphorylation of metabolic enzymes (10-15 min), 3. Effects on mRNA translation and DNA transcription (hours-days)

  
• Insulin receptors


  • Cell surface enzyme-linked receptors
• Actions of insulin


  • Increases glucose transport, glycogen synthesis, gene transcription & cell growth
  • Decreases gluconeogenesis, lipolysis, protein breakdown
  • Increases fatty acid synthesis, amino acid uptake into muscle, glycolysis

  
• Regulation of glucagon secretion


  • High plasma glucose inhibits
  • Low plasma glucose stimulates
  • High free fatty acids stimulates
  • High free amino acids stimulates
  • Sympathetic stimulation/adrenaline stimulates
  • Gastrointestinal hormones stimulate
  • Somatostatin inhibits

  
• Actions of glucagon


  • Increases glycogenolysis, gluconeogenesis, lipolysis, ketogenesis
  • Decreases glycogen synthesis, triglyceride synthesis
• Diabetes mellitus


  Syndrome of impaired metabolism caused by either deficiency in insulin secretion (Type 1) or insulin resistance AND impaired insulin secretion (Type 2)
• Type 1 diabetes mellitus


  • Characterised by failure of b cells to secrete insulin, usually rapid onset, less than 10% of all diabetes cases
• Type 2 diabetes mellitus


  • Characterised by gradual development of insulin resistance and attenuation of meal-induced insulin secretion, more common in older, overweight and sedentary people, more than 90% of all diabetes cases
• Complications of diabetes mellitus (Type 2)


  • Micro- and macrovascular damage (increased risk of heart attack, stroke, nephropathy, retinopathy, limb ischemia)
  • Hypertension
  • Atherosclerosis
  • Peripheral neuropathies and autonomic nervous system dysfunction
• Oral complications of diabetes


  • Increased risk of dental caries, gingivitis, periodontal disease, alveolar bone loss
  • Reduced salivary flow, decreased pH, lower salivary calcium concentration
  • Reduced blood supply to gums slowing healing and increasing infection
  • Increased susceptibility to oral mucosal diseases and fungal infections
  • Taste disturbances and neurosensory disorders affecting diet and oral hygiene
  • Oral infections can contribute to higher blood glucose levels