Exocrine and Endocrine Pancreas Flashcards
What 3 molecules does the exocrine pancreas produce?
Bicarbonate
Zymogens
Enzymes
Where do you find intercalated ducts in the pancreas and what is their role?
Found in exocrine glands.
It drains enzymes etc. from the acinus to the intralobular duct which then feeds into the pancreatic duct
What 4 substances does the endocrine pancreas produce?
Insulin
Glucagon
Somatostatin
Pancreatic polypeptide
What stimulates secretion of bicarbonate from a duct cell?
Secretin
What ion channels does Secretin activate via generation of intracellular cAMP?
K+ and Cl- channels
How is bicarbonate ultimately released into duodenum?
Secretin causes Cl- to be effluxed from cell and when it enters cell again it exchanges with bicarbonate ions from within the cell so bicarbonate ends up in lumen of duodenum
What hormone is produced by I cells in duodenum in response to fat and what does this hormone do?
Cholecystokinin (CCK) which stimulates acini cells to secrete enzymes needed for fat and protein digestion
What hormone is responsible for neutralising acidic contents coming from stomach?
Secretin - produced by S cells in duodenum
What gene is mutated in people with CF and what type of mutation is it?
Frameshift mutation in CFTR gene
What cells produce glucagon and where do you tend to find them in the islet?
Alpha cells - tend to be on ouside of islet
What cells produce insulin and roughly what percentage of cells do they make up in islets?
Beta cells - 70-75%
What do delta cells produce in islets?
Somatostatin
Where does C-peptide come from and what is the significance of it?
Released from insulin as insulin matures.
Levels can be measured to give an indication of beta cell activity
What receptors do beta cells express which allow the uptake of glucose?
GLUT2
What does the uptake of glucose into beta cells cause a rise in?
ATP
What channels does ATP act on in beta cells and what is the result of this activation?
Activates ATP-sensitive potassium channels (K-ATP) causing depolarisation
What does depolarisation of beta cells cause?
influx of calcium ions whcih triggers insulin release from vesicles
What type of receptor is the insulin receptor and what reaction can they undergo?
Tyrosine kinase - can undergo phosphorylation
What glucose channel do you find on fat and muscle cells?
GLUT4
Phosphorylation of what triggers movement of GLUT4 to cell surface of fat and muscle cells?
IRS-1
What is a obligatory glucose consuming tissue?
Tissue where glucose levels are NOT controlled by insulin e.g. brain
What is meant by facultative glucose consumers?
Tissues that take up glucose when they need it e.g. muscles
What is glycogenesis?
Glycogen synthesis
What happens in glycogenolysis
Liver glycogen converted to glucose
How many amino acids make up glucagon?
29
What is the structure of insulin
Alpha chain with 21aa’s and beta chain with 30 aa’s. Alpha and beta chains linked by disulphide bonds
What is the role of somatostatin and when is it released?
Inhibits release of insulin and glucagon as well as exocrine pancreatic solution.
It is produced after a meal has been digested.
Name a few symptoms of diabetes
Thirst (polydipsia)
Polyuria
Fatigue
Rougley what percentage of NHS resources does diabetes care consume?
10%
What immune cells are the main killers of beta cells in type 1 diabetes?
CD8+ T-cells (cytotoxic T-cells)
What is the key target antigen for autoimmune attack in type 1 diabetes?
Pro-insulin
Outline the natural cause theory of type 1 diabetes
That as children grow, their pancreas remodels (like everything else in body) but too much remodelling means lots of beta cells getting destroyed. immune cells clear cells which causes inflammation making immune system think there is an infection and immune system attacks beta cells
Outline the infection induced theory of type 1 diabetes
Coxsackievirus infection - molecules within this virus are similar to molecules made by beta cells so immune system will accidentally target beta cells when trying to kill virus
What are some of the genetic associations with type 1 diabetes?
Major histocompatability complex (MHC)
Immunoregulatory genes e.g. PTPN22 (a phosphatase that regulates T and B cells.
CD25 (IL-2alpha receptor) and IL-2
What is bystander activation and how is it liked to type 1 diabetes?
Immune response to infection causing damage to healthy tissue (e.g. islets) leading to release of islet antigens (beta cell antigens then get recognised as harmful)
What is the term used to describe viral proteins that resemble beta cell proteins causing the immune system to attack both?
Molecular mimicry
What type of infection is thought to trigger type 1 diabetes in children?
Enterovirus infections
What does LADA stand for?
Late Autoimmune Diabetes in Adults
Elevated levels of what helps diagnose LADA?
Pancreatic autoantibodies
What is the incidence of LADA in the UK as a percentage?
6-10%
Increased signalling of what is thought to be linked to type 2 diabetes?
Free fatty acid signalling due to increased uptake of FFAs
Where do ceramides come from and what pathway do they inhibit? What is the effect of this?
Ceramides are produced from FFA signalling and they inhibit kinase pathway PKB/Akt whcih is responsible for movement of GLUT4 channels to plasma membrane and glycogen synthesis
Are high ketone levels more diagnostic of type 1 or type 2 diabetes?
Type 1 - due to breakdown of fat
What produces ketones and what affect do large amounts of ketones have on the body?
Produced by breakdown of fat (attempt of body to get glucose).
Large amounts cause acidosis of blood which is life-threatening
Name Macrovascular complications of diabetes
Stroke
Heart disease and hypertension
Peripheral vascular disease
Foot problems
Name Microvascular complications of diabetes
Retinopathy and cataracts Renal disease Neuropathy Foot problems Erectile dysfunction
What is claudication?
cramping due to blockage of blood vessels
What affect does high glucose levels have on the immune system?
Suppresses it
What is HbA1c?
Glycated haemoglobin
What is high HbA1c a sign of?
Diabetes - Sign that there is extra glucose in blood that is not being taken up by cells so something is wrong.
RBCs last 120 days so allows you to look at glucose levels over a long period of time
