The endocrine pancreas Flashcards
What is the exocrine part of the pancreas?
• Pancreatic acini
What are the cells of the endocrine pancreas?
- Islets of langerhans
- A cells produce glucagon
- B cells produce insulin
- D (delta) cells produce somatostatin
- F cells produce pancreatic polypeptide
What are the main functions of the endocrine pancreas?
- Control of blood glucose in absorptive and post absorptive states
- Stimulate/inhibit digestive enzymes and HCO3- secretion in the GI tract
Describe the position of the cells in the islets of langerhans
- Beta cells tend to be in the centre
* Alpha cells on the periphery
What is the blood flow in the islets?
From the centre to the periphery
Describe the synthesis and processing of insulin
- Preproinsulin
- Translocated into the ER and folds into its tertiary structure
- C connects A and B chains of insulin
- The C chain is cleaved
- Disulfide bonds hold the A and B chain together
What factors increase the release of insulin?
- Free fatty acids
- GI tract hormones - GIP/GLP-1/CCK
- Certain amino acids
- Increased blood glucose
- Parasympathetic stimulation (Ach)
- beta adrenergic stimulaiton
- Glucagon
Describe the mechanism of insulin release
- Glucose enters the cell via a GLUT2 Transporter which mediates the facilitated diffusion of glucose into the cell
- This increased glucose influx stimulates glucose metabolism, leading to an increase in ATPi or in ATPi/ADPi
- The increased ATP and/or ATP/ADP inhibits an ATP sensitive K+
- Inhibition of this K+ channel causes Vm ti become more positive (depolarisation)
- This depolarisation activates a calcium channel in the plasma membrane
- Causes a Ca2+ influx, increasing intracellular Ca2+ causing Ca2+ induced Ca2+ release
- Elevated [Ca2+]i leads to the exocytosis and release of insulin secretory granules into the circulation
- CCK and acetylcholine also modulate secretion via the andenylyl cyclase cAMP - protein kinase A pathway an dphospholipase C phosphoninositide pathway
What are the effects of insulin?
• Increased protein synthesis
• Increased glycogenesis
- increased glucose transport into cells
• Increased lipogenesis
What increases glucagon secretion
- Certain amino acids
- Decreased blood glucose
- Parasympathetic innervation
- B adrenergic stimulation - adrenaline
- Alpha adrenergic stimulation
What inhibits the release of glucagon
- Insulin released by the beta cell
- Amylin
- Somatostatin by the delta cell
What are the effects of glucagon
• Decreased lipogenesis, increased lipolysis
- increased free fatty acids, increased glycerol
• Increased glycogenolysis
• Increased gluconeogenesis
What are the effects of hyperglycaemia
- Glycosuria - tubular fluid exceededs renal threshold for reabsorption (saturated SGLT 1 + 2)
- Polyuria - osmotic diuresis due to glucose in tubular fluid - more water into the tubule
- Polydipsia - dehydration increases angiotensin II levels which act as dipsogen on thirst centres in the brain
- Increased blood amino acids - due to increased protein catabolism
- Increased FFA and glycerol - due to increased protein catabolism
- Keto acidosis - due to incomplete oxidation of fatty acids and ketogenic amino acids
Describe how ketonuria occurs
- Free fatty acids/ ketogenic amino acids
- Acetyl coA -> beta-OH-butyrate
- Acetone and increased plasma ketones
- Acetone can be made into plasma ketones
- Ketonaemia
- Ketonuria
Describe the glucose tolerance test of a diabetic subject
- Starved glucose levels are higher than in normal subjects
- After glucose is given, no insulin is produced and blood glucose rises greatly
- Falling glucose mainly due to a loss of glucose through the urine
