S7 Pancreas Flashcards
Where is the pancreas located?
Behind the stomach, on the left side of abdomen, with the duodenum on the right
What part of the gut does the pancreas develop from? And what is it’s blood supply?
The foregut
Coeliac trunk artery
What are the two main functions of the pancreas? Which is the major function?
- exocrine - produces digestive enzymes that are secreted into the duodenum
- endocrine - hormone production
Exocrine
What 7 polypeptide hormones are secreted by the pancreas?
- insulin
- glucagon
- somatostatin
- pancreatic polypeptide (PP)
- ghrelin
- gastrin
- vasoactive intestinal peptide (VIP)
What cells secrete insulin and glucagon?
Beta cells and alpha cells
Which cells secrete somatostatin, PP, ghrelin and gastrin?
Delta cells, PP cells, e cells, G cells
What are the target tissues of insulin?
Liver, adipose and skeletal muscle
What are the target tissues of glucagon?
Liver and adipose
Which metabolic reactions do insulin and glucagon effect?
Insulin - carbs, lipids, proteins
Glucagon - carbs and lipids
Insulin and glucagon are either anabolic or catabolic, which is which?
Insulin - anabolic
Glucagon - catabolic
What is the normal plasma glucose range?
3.3-6mmol/L (UHL reference range)
What is the renal threshold for plasma glucose level? What occurs if this is reached?
10mmol/L then glycosuria occurs (glucose in urine)
Are insulin and glucagon water or lipid soluble? How does this mean it’s transported in the blood?
Water soluble
It dissolves in the plasma (no need for transport proteins)
What is the half life of insulin ad glucagon?
5 minutes
What is margination?
Movement of storage vesicles to the cell surface
What is exocytosis?
Fusion of vesicle with plasma membrane, releasing vesicle products out of cell
How is insulin synthesised in beta cells?
- Pre-proinsulin is translated, signal cleavage occurs, proinuslin is folded (at rough ER)
- Proinsulin is transported to the Golgi
- Proinsulin is cleaved to produce insulin and C-peptide
What is the structure of insulin?
A peptide with an alpha helix structure
- two unbranched peptide chains, c-peptide between them
- 3 disulphide bonds (increase stability of insulin)
What are K(ATP) channels?
Channels in pancreatic beta cells that are sensitive to ATP - a high ATP concentration closes these channels, higher AMP opens them
How does glucose stimulate insulin secretion?
- High plasma glucose levels. Glucose enters beta cells through GLUT2 transporters
- Glucose is then phosphorylated to glucose-6-phosphate by glucokinase and this enters the Krebs cycle and oxidative phosphorylation leading to a rise in the ATP/AMP ratio
- High ATP inhibits K(ATP) channels and reduces K+ effluent
- So the membrane depolarises causing Ca2+ channels to open, intracellular Ca2+ levels increase
- Ca2+ triggers exocytosis of insulin-containing granules
- Membrane is repolarised
What does insulin do?
- increase glucose uptake into target cells and glycogen synthesis via insertion of GLUT4 channels
- inhibits breakdown of fatty acids
What are the effects of insulin in the liver?
- increases glycogen synthesis by stimulating glycogen formation and inhibit breakdown
- inhibits breakdown of amino acids
What are the effects of insulin in the muscles?
Increases uptake of amino acids which promotes protein synthesis
What are the effects of insulin in adipose tissue?
Increases the storage of TAGs
Why type of receptor is the insulin receptor?
Tyrosine kinase receptor
Has an alpha chain subunit (on exterior cell membrane) and a beta chain subunit (integral)
How is glucagon synthesised and secreted?
- Synthesised in rough ER and then transported to Golgi
- Packaged into granules
- Margination
- Exocytosis
When is glucagon secreted?
When there are low glucose levels in alpha cells
What is the structure of glucagon?
- one chain
* no disulphide bridges - so is flexible
What are the effects of glucagon?
- increase rate of glycogen breakdown in liver (glycogenolysis)
- stimulates synthesis of glucose from amino acids (gluconeogenesis)
- stimulates lipolysis to increase plasma fatty acid
How is glucagon used clinically?
Used as an emergency medicine when a person with diabetes becomes hypoglycaemic and can’t take sugar orally
How quick can insulin effects be?
Can be:
- rapid (seconds) - a.a. and glucose uptake
- intermediate (minutes)
- delay (hours) - lipogenesis
What is diabetes mellitus characterised by?
- chronic hyperglycaemia
* leading to long term clinical complications
How is diabetes mellitus diagnosed?
- fasting blood test (plasma glucose conc over 7mM)
- random blood test (plasma glucose conc over 11.1mM)
- HbAc1
What is type 1 diabetes mellitus caused by?
Absolute insulin deficiency due to autoimmune destruction of beta -cells
What is type 2 diabetes mellitus caused by?
There’s normal secretion but relative peripheral insulin resistance due to defective insulin receptor mechanism (change in receptor no. and/or affinity), defective post-receptor events (tissues insensitive to insulin), excessive glucagon secretion
How can an insulin deficiency arise?
Due to a mutation of the K(ATP) channel meaning channel is less sensitive to ATP (gain of function)
What can insulin resistance result from?
- genetic factors
* environmental factors e.g. obesity, sedentary lifestyle
What happens if insulin resistance is present before a child is 12 years old?
- Beta cells manage to compensate by increasing the insulin production and maintains the normal blood glucose
- But then cells are unable to maintain the increased insulin production
- Beta-cell dysfunction leads to relative insulin deficiency
