glucose homeostasis Flashcards
What is hypoglycaemia and hyperglycaemia?
hyperglycaemia-high blood sugar levels
Hypoglycaemia -low blood sugar levels
What is the blood glucose concentration for hypoglycaemia?
below normal levels of 4-5mmol/L if below 2mmol/L =unconsciousness, coma and ultimately death if untreated
What kind of diabetes is a result of hyperglycaemia?
Diabetes mellitus
Which hormones increase blood glucose? Which hormones decrease blood glucose?
decrease-insulin Increase-Glucagon, cortisol, Growth hormone(GH), Catecholamines
What percentage of people in the UK are affected by diabetes mellitus?
7%
What is the % increase risk of a person with diabetes mellitus dying relative to an age matched control without diabetes mellitus?
34%
How much of the NHS budget is spent on diabetes mellitus?
10%
What are the different types of Diabetes mellitus list from most prevalent (1) to least(3)?
1-Type 2 diabetes mellitus 2-Type 1 diabetes mellitus 3-Maturity onset diabetes of the young
What 3 key components make up the pancreas?
-Head of the Pancreas -Body of the pancreas -Tail of the pancreas-Where insulin is made in the beta cells
What is the main function of the pancreas?
98% generates EXOCRINE SECRETIONS
EXOCRINE ACINAR CELLS in the pancrease release enzymes via duct into the small intestine to aid with digestion
Main function-exocrine
How much of the pancreas is involved in endocrine function?
2% of the gland made up of islets of Langerhans
What 3 cell types make up the islets of langerhan and what do they secrete?
alpha cells-Glucagon Beta cells-Insulin delta cells-Somatostatin
What are in between the cells in the Islets of Langerhan and what does this allow?
GAP JUNCTIONS-allow small molecules to pass directly between cells enabling them to communicate via PARACRINE COMMUNICATION (because if one hormone increases it tells neighbouring cell types to stop the release of other hormones) TIGHT JUNCTION-create small intercellular spaces (hormones also released into this part to enable communication too
What do the hormones releases from the pancreas do in basic terms?
Insulin-stimulates growth and development and REDUCES blood glucose by encouraging cells to take up glucose Glucagon-INCREASES blood glucose# Somatostatin-inhibits both insulin and glucagon
What stimulates beta cells to secrete Insulin?
- When you eat glucose
- some amino acid(from food we eat)-also stimulates beta cells to secrete insulin
- some GI hormones also stimulate beta cells to secrete insulin
- When your relaxed after a meal PNS activity stimulates insulin section from beta cells (however SNS activity e.g fight or flight inhibits beta cells to prevent insulin secretion)
- Glucagon increase=glycogen broken down into glucose which is released into the bloodstream = increase blood glucose = increase insulin secretion
What does insulin mainly do?
It is a hormone of anabolism meaning it helps build up our stores and reduce blood glucose -encourages liver to take up glucose(via GLUT 2) to store as glycogen(GLYCOGENESIS)
- increases the rate of glycolysis(breakdown of glucose into atp)
- increases glucose uptake into cells via GLUT-4 transporters(adipose and muscle cells)
What are additional acts of insulin?
-increases up amino acid transport=increase protein synthesis =reduces fat breakdown and increase fat build up (building stores)
A person with type 1 diabetes mellitus eats a big mac. What would you expect their c-peptide to be?
Low because they cant make their own insulin and as a result c peptide is not made
What happens when blood glucose decrease?
- stimulates alpha cells to secrete glucagon
- Some amino acids also stimulate alpha cells to release glucagon
- Some GI hormones increase glucagon secretion from alpha cells
- PNS and SNS activity causes alpha cells to secrete more glucagon
- Increase Insulin=decrease glucagon secretion
What are the 3 ways in which Glucagon increase blood glucose levels?
-Increase breakdown of fat-help form more glucose by increasing gluconeogenesis -Increase amino acid transport uptake into the liver =increase gluconeogenesis -Mainly helps break down glycogen stores in the liver to produce glucose (hepatic glycogenolysis)
What is : -Hepatic Glycogenolysis -Gluconeogenesis -Glycogenesis ?
Hepatic Glycogenolysis-Break down of Glycogen to glucose in the liver Gluconeogenesis-making glucose from non carbohydrate pre cursors e.g. Amino acids Glycogenesis- glucose joined to make glycogen
How is insulin secreted fro the beta cells?
1-glucose enters beta cells via GLUT
2 transporters (not insulin dependent) 2- Glucose-> Glucose 6 phosphate via enzyme GLUCOKINASE (Hexokinase 4- thought to be main glucose sensor)(this is a rate limiting step )
3-Glucose 6 phosphate converted into ATP
4-ATP blocks channels at cell membrane surface which leads to the release of potassium
5- Potassium in the cell stimulates the VGCC at the cell surface membrane
6-calcium enters the cell resulting in the release of stored insulin and the synthesis of new insulin if glucose is above a certain threshold
In what form is insulin stored in the cell and how is this converted back to insulin?
-Stored as PROINSULIN(polypeptide made up of 53 amino acids) -Proinsulin undergos PROTEOLYTIC CLEAVAGE resulting in the release of C-PEPTIDE chain and 2 chains of insulin which are bound together via dipeptide bonds
How can we measure insulin in the body?
Measure C-peptide concentration
What would happen to the C-peptide concentration in the body after eating
Inrease -because glucose in food stimulates insulin secretion -some amino acids in food stimulate insulin secretion -food in stomach means GI hormones release which also stimulates insulin release Insulin secretion is accompanied by c-peptide as both are a product of proinsulin cleavage
What is the gastrointestinal incretin effect?
Insulin production is much greater in response to oral glucose relative to the same quantity of glucose administered intravenously. This so-called ‘incretin effect’ is attributed to signals and hormones arising from the gut after the ingestion of glucose that potentiate insulin release from pancreatic beta cells
What is the key hormone involved in the incretin effect?
Glucagon like peptide (GLP-1)
What is GLP-1?
Gut hormone secreted in response to nutrients in the gut, mostly from L-CELLS -stimulates insulin secretion, supresses glucagon secretion -Promotes satiety as levels increase after a meal -Has a short half life due to rapid degradation from the enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor) -Used in treatments of diabetes mellitus (as this hormone is lower in people with type 2 ) -GLP is injected to people -has a secondary effect of weight loss
What kind of insulin do we have relate this to type 2 diabetes?
Stored insulin and insulin we make in response to glucose immediately People with type 2 diabetes have less stored insulin
What is the first phase insulin release?
When after we have glucose their is a rapid increase in plasma insulin this insulin decreases in a curve within time span of 2 hours (look up graph for this) there is no spike with people who have type 2 diabetes
Describe the insulin receptor?
Has a beta subunit within the membrane, and then an extracellular alpha subunit that sits on top of the beta subunit Insulin binds to the alpha subunit
What happens when insulin binds to its receptor?
conformational change in the TYROSINE KINASE domains of the beta subunits(the part of the subunit that is in the cell) This allows insulin to take effect
