Pancreas Anatomy Flashcards
What does the pancreas develop from?
The organ develops as outgrowth of the foregut (dorsal and ventral) and the Langerhans islets bud off from the developing exocrine pancreas.
What is the function of the exocrine pancreas?
Secretes digestive enzymes- Secreted in response to gastrointestinal hormones (e.g. cholecystokinin; CCK)
Also secretes bicarbonate (base) to neutralize acid produced in the stomach-
Secreted in response to secretin (hormone produced by intestinal cells)
Where is the endocrine pancreas situated?
The endocrine compartment of the pancreas is concentrated in the islets of Langerhans (1-2% of the pancreas)
What cells does the endocrine pancreas consist of?
β-cells (dog:75 %)
α-cells (dog: 20 %)
δ (delta)-cells
What do the cells of the islet produce?
β-cells which produce Insulin (dog:75 %)
α-cells which produce Glucagon (dog: 20 %)
δ (delta)-cells which produce Somatostatin
Other hormones also produced by the islet cells include:Pancreatic polypeptide, ghrelin, vasoactive intestinal peptide (VIP), secretin, motilin, and substance P
What is different about the horse pancreas?
The lobes are fused
Which species have fused pancreas lobes (partially)?
Ox, sheep and pig
Where does the pancreas arise from
The final liver and pancreas are made from glandular tissue from the gut plus connective tissue from mesenchyme.
Where is somatostatin produuced?
Hypothalamus (periventricular nucleus)
Stomach
Intestine
Pancreas (delta cells)
What does somatostatin from the delta cells do?
Acts to supress insulin and glucagon secretion by local beta and alpha cells
Why does insulin need to be injected rather than taken orrally?
Insulin is a peotide hormone which means that it needs to be injected otherwise it would be digested
How is insulin produced?
It is Secreted by the beta cells of the Islets of Langerhans where it is first synthesized as a preprohormone and then converted to a prohormone called proinsulin
What is the purpose of making insulin as a prohormone?
This forms an Intracytoplasmic pool of proinsulin
What is the C-peptide and how is it formed?
Secretion of insulin involves the removal of C-peptide from proinsulin, C-peptide is the connecting peptide.
The C-peptide is then released with the insulin but it is biologically inactive
How can we use C-peptide?
Because it is removed from the body at a slower rate it is useful to measure pancreatic function (but not often done in animals)
What does the insulin molecule consist of?
Insulin molecule consists of two polypeptide chains of length 21 (α) and 30 (β) amino acids.
These two chains are connected by two disulphide bonds
Where is insulin degraded?
Degradation of insulin is done in the liver and kidneys within target cells after the insulin binds to the receptor and is broken by cleavage of these disulphide bonds
What is the half life of insulin?
Once insulin is secreted by the pancreas it has a half life of only 5-8 min
Once secreted by the liver what is the action of insulin?
It enters the veins and goes into the portal system where it travels to the liver where the insulin acts first.
After this insulin enters the general circulation although the C-peptide is not removed from circulation by the liver
Insulin secretion is regulated by…
Nutrients: glucose and amino acids Gastrointestinal hormones (incretins) such as gastric inhibitory peptide (GIP) and glucagon like peptide (GLP-1)
Autonomic nervous system
a. Parasympathetic stimulates
b. Sympathetic inhibits
Insulin is an anabolic hormone, what does this mean?
Increased secretion when nutrients are abundant eg. After feeding
How does calcium have an effect on insulin release?
The release of insulin from β cells occurs through the process of calcium-mediated exocytosis and acts to move energy substrates into storage
How do GI hormones regulate insulin release?
Insulin secretion is stimulated by gastric inhibitory peptide (GIP) and GLP-1 which are Released by small intestinal cells
There is an Increase in GIP and GLP-1 when food reaches intestine which causes insulin release from pancreas before nutrient absorption occurs
What effect does parasympathetic stimulation have on insulin secretion?
The parasympathetic nervous system stimulates insulin secretion via the the vagus nerve (the vagus also increases GI motility and digestion) so this creates higher insulin after feeding
What effect does sympathetic stimulation have on insulin secretion?
There is also direct innervation by sympathetic neurons (and indirect sympathetic stimulation via adrenaline) which initiates a stress response, hyperglycemia, so insulin secretion is inhibited
What is first and second phase insulin release?
First phase represents release of the intracytoplasmic pool of proinsulin
Second phase insulin secretion results from new protein synthesis
How does insulin bind to receptors?
Insulin is a water-soluble peptide hormone so it binds to insulin receptors on plasma membranes
The density of insulin receptors is dependant on…
The density of receptors is one determinant of insulin sensitivity
Activation of these insulin receptors causes activation of what pathway?
Activation of these receptors activates the tyrosine kinase signal transduction pathway
What are GLUT4 proteins and what does insulin stimulate them to do?
GLUT4 proteins are the insulin-responsive glucose transporters in skeletal muscle and adipose tissues (Major sites for nutrient storage)
Insulin stimulates translocation of glucose transporter 4 (GLUT4) proteins from the cytoplasmic vesicles to the plasma membrane
Insulin increases glycogen ……………….
synthesis
In the liverthere are no GLU4 receptors so how is insulin taken up?
Via GLUT2 receptors?
Liver uptake of insulin acts to …..
Inactivate liver glycogen phosphorylase (which inhibits glycogenolysis)
Increase glycogen synthase activity (which stimulates glycogenesis)
Promotes conversion of glucose into fats (stimulates lipogenesis)
Inhibits gluconeogenesis
There are no GLUT4 receptors in the brain so how is insulin taken up?
GLUT1
The Exception is where insulin is taken up into satiety and appetite centres (without insulin appetite increases)
What effect does insulin have on hormone sensitive lipase?
Insulin also inhibits hormone sensitive lipase (HSL) which decreases lipolysis and stimulates lipogenesis (production of fatty acids from glucose)
What are the steps in lipogenesis?
Excess glucose increases TCA cycle intermediates: citrate and isocitrate
Activate acetyl CoA carboxylase (ACC)
Forms malonyl CoA (fat precursor)
What is the effect of insulin on protein metabolism?
Increasing amino acid uptake by tissues and increasing the rate of transcription and translation, it also inhibits the catabolism of proteins.
What is the effect of insulin on the rate of gluconeogenesis?
Insulin depresses the rate of gluconeogenesis within the liver and inhibits enzymes so lowers supply of AA from tissues.
Where is glucagon secreted from?
Glucagon is secreted by by alpha cells of the Islets of Langerhans
What is glucagon and how is it synthesised?
It is a petide hormone consisting of 29 amino acids that is synthesized as preproglucagon which is rapidly converted to glucagon.
What is the half life of glucagon? Where is it metabolised?
It has a short half life of 5-6 mins and is metabolized in the liver and kidneys
What triggers the alpha cells to produce more glucagon?
Alpha cells primarily respond to a low blood glucose level (hypoglycemia)
What is the function of glucagon?
Glucagon acts to maintain blood glucose levels between meals and is activated during negative energy balance, it stimulates glycogenolysis and gluconeogenesis.
What stimulates and inhibits glucagon?
Glucagon is inhibited by by high blood glucose levels and Stimulated by high amino acid levels (eg. After a protein rich meal, it responds best to Alanine and arginine) which promotes gluconeogenesis to act in a protective mannor.
