Pancreas Physiology Flashcards
What are the exocrine functions of the pancreas?
Pancreatic acini secrete enzymes (in form of zymogens) active in protein , fat and carb digestion (typsin, lipase and amylase)
List the cell types in the Islets of Langerhans and the substances they secrete
- alpha (A) cells: glucagon
- beta (B) cells (65%): insulin and amylin (opposes insulin)
- delta (D) cells: somatostatin
- epsilon (E) cells: ghrelin (aids digestion)
- PP (F) cells: pancreatic polypeptide
What are the main functions of the islets of Langerhans in the pancreas?
- control blood sugar concentration in absorptive and post-absorptive states (with insulin and glucagon)
- stimulate/inhibit digestive enzymes and bicarbonate (HCO3-) secretion in the GIT
Describe the role of insulin and glucagon
Insulin is responsible for transport of glucose into cells in absorptive phase of digestion.
Glucagon is responsible for mobilising glucose from glycogen stores in the liver during post-absorptive phase.
What protects somatostatin from being broken down after release from the pancreas?
It is a cyclic peptide and that conformation prolongs its lifespan
Describe the synthesis of insulin
- insulin gene transcribed in nucleus (exons are fused together to form mRNA)
- gives 5’ translated region that directs mRNA out of nucleus into cytosol to ribosome on the rough ER
- preproinsulin mRNA starts translation
- signal sequence is encoded from protein during translation from N-terminus
- recognised by trafficking proteins which direct peptide as it is being synthesised into the lumen of the ER
(important in correctly routing insulin into its secretory pathway)
Describe the secretory pathway of insulin
- signal sequence of protein is cleaved off once it enters the ER
- disulfide bonds start to form as insulin adopts most energetic favourable arrangement
- in trans-Golgi network ezymes target c-peptide from A and B chains of pro-insulin
- allows most of pro-hormone to be cleaved into the mature insulin molecule with c-peptide being cleaved off and stored in the beta cell secretory granule
- in the granule insulin and zinc bind to specific proteins
- interactions help concentrate and crystalize insulin facilitating dense packing of molecule and limit osmotic effect
Describe the microvasculature of the endocrine pancreas
- each islet is encapsulated and innervated with a capillary bed (with an arterial end and a venous end)
- allows for rapid delivery of pancreatic hormones into circulation
Describe the effect of nervous system stimulation on insulin
activation of PSNS causes stimulation of insulin secretion (stimulation of vagus nerve causes release of ACh of post-synaptic fibres causing binding to muscarinic receptors)
activation of SNS causes inhibition of insulin secretion (stimulation of splenic nerve which causes release of noradrenaline which binds to alpha-2-adrenoreceptors)
BUT if noradrenaline binds to beta-adrenoreceptors then this stimulates insulin secretion
Describe the regulation of insulin through digestion
- insulin is secreted in absorptive state when food begins digestion in GIT
- increase in blood glucose concentration is main stimulus
- carbs are liberated in the GIT, transported to the blood in the form of glucose and flows to the beta cell (sensor for glucose)
- raises metabolic rate of beta cell which raises insulin secretion
- insulin goes into circulation to work on various organs and tissues to decrease glucose levels and increase glycogen storage in the body
Describe the potentiation of insulin release through amino acids/free fatty acids
- eg. leucine/isoleucine
- enter blood after protein and fat digestion
- induce more insulin release in presence of high glucose
- further increase metabolic rate of beta cell to promote larger release of insulin
Describe the potentiation of insulin secretion through gut hormones
- signal arrival of food to beta cell
- activated by passage of food in GIT in response to high glucose or lipids
- release hormones which have receptors on beta cells to further promote further insulin release
Describe the effect of paracrine secretion on insulin release
- exert their effects when glucose levels are high
- glucagon released from A cell potentiates insulin release
- somatostatin released from D cells inhibits both insulin release and inhibits the action of A cells
Describe the cellular mechanisms of insulin release from the beta cells
- glucose enters the beta cell by GLUT2 transporter at the membrane (down its conc gradient)
- it undergoes glycolysis (phosphorylated by glucokinase to form glucose-6-phosphate into pyruvate)
- pyruvate feeds into citric acid cycle to generate ATP (generating beta cell metabolism)
- increase in ATP ratio to ADP leads to ATP binding to K+ channel causing it to close preventing efflux of K+ outside of beta cell
- this causes depolarisation of the membrane which opens voltage gated Ca2+ channels causing influx of calcium down its concentration gradient
- this binds to receptors on ER opening channels and inducing release of more calcium from internal stores which activates proteins in exocytotic pathways leading to the exocytosis of secretory granules containing insulin into the blood
Describe the cellular mechanisms of augmentation of insulin release from beta cells by CCK
CCK binds to its receptor (g-protein coupled) activating Gq pathways leading to PLC activation and generation of IP3, DAG (secondary messengers)
- IP3 will bind to receptors on ER increasing Ca2+ release potetiaing insulin secretion
- DAG activates PKC which phosphorylates a number of proteins causing increased exocytosis of insulin granules
