ENI - Pancreas Flashcards
Describe the exocrine pancreas
- Large component
- Secretes digestive enzymes
- Secretes bicarbonate
- Digestive enzymes include: trypsin, carboxypeptidase, lipase, phospholipase, amylase, ribonuclease, deoxyribonuclease
Describe the endocrine pancreas
- Concentrated in islets of Langerhans (1-2% of pancreas)
- 3 cell types
- Beta: insulin (60-70%)
- Alpha: glucagon (20-25%)
- Delta: somatostatin (10%)
- Also pancreatic polypeptide, ghrelin, vasoactive intestinal peptide (VIP) secretin, motilin and substance P
Describe somatostatin
- Produced by hypothalamus (PVN), stomach, intestine, pancreas
- Paracrine function
- Suppresive to insulin and glucagon secretion by local beta and alpha cells
Describe the synthesis of insulin
- Peptide hormone
- First: preprohormone
- Converted to prohormone (proinsulin)
- Have intracytoplasmic pool of proinsulin waiting for relase
- Secretion involves production of insulin from proinsulin
- Removal of C-peptide connecting 2 polypeptide chains which make up insulin (alpha and beta chains)
- These chains are connected by 2 disulphide bonds
Describe the secretion of insulin
- From beta cells
- Involves remoal of C-peptide from proinsulin
- Enters veins, into portal system, to liver, acts on liver first, then rest enters general circulation
- 3 mechanism of regulation
Describe the degradation of insulin
- In liver
- Within target cells after receptor binding
- Involves cleavage of 2 disulfide bonds
What are the 3 mechanisms of insulin secretion regulation?
- Nutrients
- Gastrointestinal hormones
- Autonomic nervous system
Outline how nutrients regulate insulin secretion
- Glucose and amino acids
- insulin secreted when these are high
- Action of insulin is to promote formation of storage molecules
Outline how gastrointestinal hormones regulate insulin secretion
- Incretins
- e.g. gastric inhibitory pepide (GIP and glucagon like peptide (GLP-1)
- Promote release of insulin (as incretins are relased at feeding want to use nutrients in storage moleucles)
Outline the autonomic nervous system regulation of insulin secretion
- Parasympathetic stimulates via vagus, increases gastrointestinal motility and digestion, higher insulin after feeding
- Sympathetic inhibits, direct innervation, indirect responses via adrenaline, stress response = hyperglycaemia, insulin secretion and action inhibited
Outline the mechanism of release of insulin
- GLUT2 transporters allow glucose into beta cell
- Phosphotylation of glucose by glucokinase, traps glucose in cell
- Increase in ATP production
- Inhibits ATP-sensitive potassium channels
- Increased intracellular potassium concentration leads to depolarisation
- Voltage-gated calcium channels activated
- Influx of calcium triggers exocytosis of insulin
What type of hormone is insulin?
Water soluble peptide hormone
What signal transduction pathway is used by insulin?
Tyrosine kinase
What are the cellular actions of insulin binding to its receptor?
- Activates tyrosine kinase signal transduction pathway
- Tyrosine kinase mediated signalling system promotes glycogen synthesis and other storage activities
- Movement of GLUT4 to memrbane so can be a receptor for glucose
Describe the GLUT4 receptors
- Insulin stimulates translocation of GLUT4 proteins
- From cytoplasmic vesicles to plasma membrane
- Insulin responsive glucose transporters
- In skeltal muscle and adipose tissue are major sites for nutrient storage