pancreas Flashcards
what is the need for blood glucose?
- Ubiquitous energy source – used by all tissues
- Glycogen is stored in reservoir of glucose – excess glucose converted in liver to glycogen
- CNS cannot substitute glucose; delivery is therefore critical – dependent on glucose in blood reaching brain
what is hypoglycaemia?
<2.5mmol/L
what is normoglycaemia?
Normoglycemia – 3-5mmol/L healthy fasting value
Normoglycemia - 7-8mmol/L healthy post-prandial (after a meal – slightly higher for digesting food)
what is hyperglycaemia/
> 10mmol/L
what is the homeostasis of hyperglycaemia?
insulin is the principle hormone which is detected when blood sugar levels rise. Insulin release is detected by pancreatic B cells.
They come about if you take food in, but also convert glucose to glycogen and you may also convert fatty acids into glucose precursors in the liver.
Overnight fasting you will use your glycogen up.
If you don’t eat for numerous days you will start to use your fatty acids sources. This all takes places within the liver.
Insulin has action on many tissues, the effect is to bring blood sugar levels back down -0 negative feedback process that doesn’t directly link to CNS. Drugs which are used usually have affect on insulin released, action or via another pathway.
what is the homeostasis of hypoglycaemia?
If following period of long fast your blood sugar begins to drop, the trigger is a fall in blood levels which leads to a release of glucagon from the pancreatic a cells, in islet of Langerhans.
Glucagon stimulated processes associated with endogenous glucose production, mainly in liver but also works in muscle.
This increases blood sugar levels and this is again negative feedback from the decrease in blood sugar. Principle drug target is the pancreatic alpha cells by using a synthetic molecule.
what is insulin?
- protein hormone
- derived from proinsulin
-23 amino acids removed from proinsulin C - ## this is then acitve and stored and released as insulin
where is insulin synthesised and stored/
- Synthesised in β-cells (islets of Langerhans) and store. Only place in body you make insulin.
- Located in β-cell secretory granules
where is insulin metabolised?
liver
what are the islets of langerhans?
located in the pancreas. Only compose around 1% of the total mass of the pancreas, so most of what the pancreas does is associated with digestion.
Discrete micro organs structures, they have got 5 different endocrine sites within them.
they have blood flowing to them and venus draining away from them, very rich blood supply. Around 25% of blood supply is bathing them at any one time.
what are the 5 endocrine sites within the islets of langerhans?
b cells release insulin a cells release glucag g cells - release somatostain e cells release ghrelin pp cells release pancreatic polypeptide
how does digestion increase blood sugar levels?
Digestion increase blood sugar levels, glucose is then taken up by beta cells in the islets, glucose is then metabolised, and the cells depolarises because of potassium channels undergoing closure. This depolarisation of membranes then causes an efflux of calcium and insulin is then released as a consequence of exocytosis. This supports first and second insulin release. The insulin released is directly linked to the amount of glucose digested.
When you digest food, the presence of food stuff in the GI tract and first appearance of sugars stimulates release of hormones from cells in GI tract. One of these hormones is GLP 1, this is realised from endocrine cells in GI tract when food is being digested. GLP1 then gets into the blood and activates specific receptors on the islet Beta cells. This activation causes cell signalling mechanisms to be turned on and insulin is then released. This pathway will not take place if glucose levels do not go up.
how does insulin lower blood sugar?
endogenous kinase activity associated with it, this binding causes activation of the receptor. This kinase activity causes a cascade of down stream signalling pathways. this switches on transporters in the membrane and causes appearance of membrane GLUT4 transporters. Once this transporter is activated you get glucose entering the cell through facilitated diffusion, lowering blood sugar levels. Relatively quick and efficient process.
activation of receptor causes a lowering in blood sugar.
why are actions of insulin anabolic?
- Increase the transport of glucose into cells
- Converts glucose to glycogen
- Decreases glycogen breakdown
- Increase fat stores
- Increase protein production
- Very effective and stopping process that makes glucose. Inhibits convert to glucose
what is diabetes mellitus?
Diabetes is a chronic disease, which occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. This leads to an increased concentration of glucose in the blood (hyperglycaemia). Cannot be cured but can be managed
