Pancreas Flashcards
How does the pancreas develop?
Embryologically as an outgrowth of the foregut
Describe the structure of the pancreas and their corresponding functions
Acinar cells - exocrine function
Islets of Langerhans - endocrine function
Outline the exocrine function of the pancreas
Acinar cells - secrete digestive enzymes
Ductal cells - secrete bicarbonate ions
What digestive enzymes are produced by the pancreas?
Proteases - trypsin + chymotrypsin
Pancreatic lipases
Pancreatic amylase
Major cells in the Islets of Langerhans and what they secrete
Beta cells - insulin
Alpha cells - glucagon
Delta cells - somatostatin
Actions of insulin
Anabolic
- increases glucose oxidation
- increases glycogen synthesis
- increases fat synthesis
- increases protein synthesis
Action of glucagon
Catabolic
- increases glycogenolysis
- increased gluconeogenesis
- increased ketogenesis
What does insulin act on?
Liver
Adipose
Skeletal muscle
What does glucagon act on?
Liver
Adipose
NOT skeletal muscle - lacks glucagon receptors
How does insulin increase glucose uptake?
Promotes GLUT4 translocation in adipose + skeletal muscle
Describe insulin
Peptide hormone
Made of 2 in branched chains held together by 2 disulphide bonds
a-helix structure
Outline insulin synthesis
DNA in B cell > mRNA > preproinsulin > proinsulin > insulin + C-peptide (cleaved off to leave insulin)
1- preproinsulin synthesised in nucleus of B cells
2- PPI sent to rough ER
3- PPI cleaved to proinsulin
4- PI folded + disulphide bridges are formed
5- PI transported to Golgi apparatus
6- PI cleaved to give insulin + C peptide
7- packaged into secretory granules for release
What is C peptide used for?
Clinical marker of synthesis of insulin
Outline insulin secretion
1- increase in blood glucose conc.
2- glucose enters B cells via GLUT2 transporter
3- increase in glycolysis > increase in ATP
4- increase in ATP:ADP ratio
5- ATP dependent K+ channels close
6- depolarisation
7- VGCC open > influx of Ca2+
8- secretory granules released via exocytosis
What stimulates insulin release?
Parasympathetic nervous system
- increased plasma glucose, aa and free fatty acids
- glucagon
- adrenaline at B cell receptor
What inhibits insulin release?
Sympathetic nervous system
- decrease in plasma glucose, aa + free fatty acids
- somatostatin
- Leptin
- adrenaline at a cell receptor
How does insulin exert its effect on cells?
1- insulin binds to insulin receptor (tyrosine kinase)
2- receptor auto-phosphorylation
3- activation of signally complexes at cell membrane 4- has effects on metabolic pathways + glucose uptake
Describe the structure of glucagon
Peptide horomone
No disulphide bonds
Outline glucagon synthesis
DNA > mRNA > preproglucgaon > proglucagon > glucagon
How does glucagon exert its effect on cells?
1- glucagon binds to glucagon receptor (GPCR)
2- G protein activation
3- effector protein activation
4- 2nd messenger formation
5- effects on metabolic pathways + gene expression
What is the half life of insulin and glucagon in plasma?
5 minutes
What type of receptor is an insulin recpeotr?
Tyrosine kinase
What type of receptor are glucagon receptor?
GPCR
Describe type 1 diabetes mellitus
Absolute insulin deficiency caused by autoimmune destruction of pancreatic B cels
Describe type 2 diabetes mellitus
Relative insulin deficiency casued by insulin resistance
