Glucose Homeostasis Flashcards
What happens when an individual becomes hypoglycaemic?
Trembling, sweating, anxious, confused, hungry, blurred sight etc.
Why is glucose important?
Within which range is glucose regulated?
Below which glucose level is cerebral function impaired?
Below which glucose level can a person become unconscious?
An important energy substrate - particularly for the CNS (brain needs glucose to survive)
Kept between 4-7 mmol/l
Below 4 mmol/l (Below 3 = clinically significant)
Below 2 mmol/l (person may fall into a coma - untreated = death)
What is the feedback system to control blood glucose levels?
Which 4 hormones help increase BGL?
What hormone reduces BGL?
Glucagon, cortisol, GH, Catecholamines
Insulin
What are the functions of the pancreas?
Why is the pancreas important for glucose homeostasis?
What are the 3 subtypes of cells of the islets of langerhan found in the pancreas and what hormones do they secrete?
Majority of pancreas is responsible for exocrine secretions that assist with digestion - travels via duct to ileum; but there are:
2% of glands that produce endocrine secretions. They are the islets of langerhan, which are important for glucose homeostasis:
Alpha, beta and delta cells of the islets of langerhan release glucagon, insulin and somatostatin respectively
Not only do the islets of langerhan release their cells intravascularly, they also have paracrine communications with each other. What is meant by this?
What are the names of the junctions that allow the cells to work together?
The cells communicate with each other by releasing hormones to their local neighbours via:
Gap and tight junctions
What are the acrions / functions of insulin, glucagon and somatostatin?
Insulin - reduces BGL; also stimulates growth and development (esp. during the intrauterine period, early childhood and adolesence)
Glucagon - increases BGL
Somatostatin - acts as an all negative response, inhibits both, insulin and glucagon
What are the physiological changes that occur in response to an increase in plasma glucose values?
What other factors stimulate the beta cells of the islets of langerhan to release insulin?
What factors inhibit release of insulin?
High BGL detected by the beta cells of the islets of langerhan, and this timulates the release of insulin
e.g. after a meal - some amino acids, some GI hormones; PNS activity; and glucagon indirectly (glucagon causes the conversion of glycogen to glucose, which increases BGL so insulin is released to counteract that); and adrenaline binding onto the beta-adrenergic receptors on the beta-cells
Adrenaline binding onto alpha-adrenergic receptors on the beta cells, SNS activity and somatostatin
What are the actions of insulin?
Increase glycogenesis - build up of glycogen stores
Uptake of glucose via the GLUT-4 receptors found on skeletal muscles and adipose tissues (fat)
Increase glycolysis - breakdown of glucose
Acts on and increases amino acid uptake - stimulates protein synthesis
Reduces lipolysis (fat breakdown) and increases lipogenesis (fat build up)
What are the physiological changes when BGL falls?
What other factors stimulate the alpha cells of the islets of langerhan to release glucagon?
What factors inhibit release of glucagon?
Glucagon is released to breakdown glycogen stores to increase BGL
e.g. some amino acids; some GI hormones; and activation of the ANS, so both, the SNS and PNS stimulate glucagon release
Insulin and somatostatin
What are the actions / functions of glucagon?
How can glucagon be used medically for T1MD?
Mainly breaks down glycogen reserves (especially within the liver) - hepatic glycogenolysis
Stimulates lipolysis, breakdown of fats, and increases amino acid uptake in the liver - both for gluconeogenesis
If a person with type 1 diabetes mellitus has a major hypoglycaemic episode, they may be given a glucagon injection so their glycogen stores in the liver are broken down and glucse is released into the blood to elevate BGL
What are the physiological changes after intense exercise?
Increase hepatic glycogenolysis, increase in lipolysis, increase uptake of amino acids into the liver
How is insulin secreted from the beta cells?
Glucose enters the beta cells via the GLUT-2 transport, which is not insulin dependent
A rate-limiting enzyme, known as glucokinase (or hexokinase IV) metabolises glucose into glucose-6-P, this kicks in when BGL is high, and is not functioning when BGL is low
Therefore glucokinase is thought to be the main glucose sensor
Glucose-6-P is then converted into ATP
ATP in turn blocks channels on the cell membrane surface, this leads to the release of K+ inside the cell
K+ stimulates the opening of VG-Ca2+ channels - Ca2+ enters the cell and stimulates the release of stored insulin and also the synthesis of new insulin
How does glucose enter B cells?
What is the rate-limiting enzyme that controls the whole process of insulin release?
What are the 2 ions involved for the ultimate release of insulin
GLUT 2 receptors - not insulin sensitive
The glucokinase enzyme - kicks into place with high BGL to produce ATP
K+ and Ca2+ - K+ causes the opening of VG-Ca2+ channels, Ca2+ enters, insulin is released
How is insulin stored in cells?
How is it converted to insulin during the time of release?
How is someone’s ability to produce their own insulin tested clinically? Why is this compound measured?
Stored as a compound known as pro-insulin (polypeptide made up of 53 amino acids)
When proinsulin is released within the cell, it is cleaved to form C-peptide + 2 chains that are bound by disulphide bonds
Test for C-peptide levels - as it is released in equal volumes to insulin, and is more stable than insulin as insulin has a shorter half-life, so is degraded quickly
What is incretin?
What is the incretin effect on BGL?
Explain what the graph is showing:
Incretin - GI hormones released after eating
They stimulate a decrease in BGL by increasing the secretion of insulin released from pancreatic beta cells of the islets of Langerhans
Graph below shows that insulin release is much greater when the same mass of glucose is ingested orally (And therefore has to travel through the GI tract), than when administered intravenously
