Glucose Flashcards
What is the fuel that your brain uses?
Acutely glucose only. But it takes it up without insulin.
Cerebral function is critically dependent on maintaining glucose levels above 3.5 mmol/L
Your brain use most of the glucose, your blood cells an kidneys use the rest.
After 2 days of starvation when you have little glucose store left your brain switches to ketone metabolism.
What consumes the glucose?
Mostly brain then red blood cells and kidneys.
What is glycogenolysis?
Break down of glycogen to glucose-6-phosphate and glycogen.
Takes place in the muscle and liver tissues. Regulates blood glucose levels.
In muscles, glucose-6-phosphate is used for glycolysis to provide energy for muscle contraction.
In the liver, glucose-6-phosphate has the phosphate removed and the free glucose exits the cells via GLUT2 into the blood.
What is gluconeogenesis?
Production of new glucose from non-carbohydrate carbon substances. Amino acids from the breakdown of proteins, FFA from lipid breakdown. Mostly done in the liver, and from pyruvate and lactate.
What is the immediate store of glucose?
Glycogen - in liver and muscles.
Where does most of the glucose we use come from?
Ingestion, from production in the liver. From stores in fat and proteins.
Glucose is ingested and manufactured by gluconeogenesis (new glucose in liver) and glycogenenolysis (convert glycogen to glucose in muscle and liver)
What is the function of insulin?
It is the key hormone in preventing uncontrolled hyperglycaemia after eating so it decrease blood glucose
It is anabolic, it increases the storage of glucose, fatty acids and amino acids (transport into insulin sensitive cells).
Insulin is turned on while eating and Conversely, glucagon is turned off.
It inhibits lipolysis and therefore the production of ketones.
What is the function of glucagon?
It is a key hormone keeping blood glucose from falling into hypoglycaemic range (increases blood glucose)
it is catabolic, increases the mobilization of glucose, fatty acids and amino acids from stores.
In fasting situation, glucagon will be turned n and insulin turned off.
What is an islet of langerhan?
Endocrine tissue in the pancreas. It is highly vascularized to allow fast transmission of hormones to the blood.
Consists of - beta cells (core) - insulin to decrease glucose
alpha cells - outer edge of islet - glucagon to increase glucose
Delta cells - (scattered) - somatostatin (growth hormone inhibiting hormone) decreases insulin and decreases GH.
F cells (pancreatic polypeptide for bicarbonate regulation.
There is a paracrine interaction between beta and alpha cells.
Neurovasclar bundle enters each islet through the beta cell core (endocrine function more concentrated in the tail than the body)
Where is the blood from the pancreas drained to?
The portal vein and liver
What is pancreatitis?
Digetive enzymes from the pancrease are released into the pancreatic tissue which degrades the pancreas. This can damage the islets of langerhans and they can subsequently develop diabetes.
What is a treatment for pituitary tumours that produce too much GH?
Somatostatin analogues. Can also be used for type 2 diabetes because somatostatin will decrease insulin release.
How is glucose taken into cells?
There is insulin mediated and non-insulin mediated glucose transporters.
GLUT1-7 - transporters that transport proteins at different cells in the body
GLUT1 - found in the erythrocytes and brain (non-insulin)
GLUT2 (non-insulin mediated glucose transporters) - found in the pancrease beta cells and liver
GLUT3 - neurons and placenta
GLUT4 - fat and muscle (insulin mediated) - also exercise induced to reduce glucose
GLUT107 has no homology with SGLT1-2.
SGLT1 found in the small intestine
SGLT2 found in the kidneys to reabsorb glucose into the blood in he proximal nephron.
What happens to patients with SGLT2 mutations?
Glucose in teir uine but their blood glucose is normal.
Glucose of >10 mmol/l will cause urine to be lost in the urine.
drugs to block causea decrease in the glucose level required to cause it to be excreted.
What induces insulin release?
Glucose enters the beta ell of the pancreas via non-insulin mediated uptake (GLUT2)
The glucose then undergoes glycolysis to form ATP. Glucose is converted to glucose-6-phospate by glucokinase phosphorylate. The ATP closes the ATP-sensitive potassium channels resulting in cell depolarisation.
Calcium then enters the cells via voltage gated calcium channels which triggers insulin translocation and exocytosis.
Glucagon-like peptide (GLP-1) can mimic glucose and cause insulin resistance and reduced blood glucose.
How is insulin produced?
Preproinsulin is a long chain which consists of an A, B and C peptides and a signal sequence. Proinsulin is made from preproinsulin when the signal sequence is cleaved away.
Insulin has an A and B chain bound by disulphide bondes. C peptide is cleaved away.
For every molecule of insulin releases a C peptide.
Chain B has positive charge and it can be modified for short acting and long acting insulin drugs.
C peptide can be used as a marker. Death by insulin can be identified because there is no C peptide produced (factitious hypolglycaemia).
How is Insulin regulated and what regulates it?
Basal secretion is pulsatile (9-14 minutes).
Major regulator is glucose with fast active phase release (insulin burst, lost in type II diabetes) and a slower second phase.
Other regulators are amino acids such as arginine, glucagon, incretins, somatostatin.
Insulin release in response to increased glucose, increased glucagon, vagus stimulation arginine.
Insulin inhibited by falling glucose, sympathetic nerve stimulation, release of somatostatin.
What do adrenaline, GH and cortisol do to glucose levels?
Adrenaline, growth hormone and cortisol reduce insulin receptor number and affinity, which result in a degree of insulin resistance. Their main action however is on gluconeogenesis and glycogenolysis and protection from hypoglycaemia.
What do incretins do?
Ingestion of food leads to increting gut hormones being released (GLP-1), which results in reduced glucagon release from alpha cells, increased insulin release from beta cells.
Increased glucose -> more GLP-1 to decrease production of gluocose and increase insulin secretion.
What does insulin signalling do?
It causes a phosphorylation cascade and translocation of GLUT4 proteins to the plasma membrane. This allows glucose to enter muscle and fat cells thus reducing blood glucose.
What does insulin do to proteins, fat and carbohydrates?
Protein: increases the transport of amino acids into the liver and muscles
Fat: increases triglyceride storage, inhibits lipolysis (reduced lipase function), which inhibits FFA production and therefore inhibits ketone production
Carbohydrates:
Liver - insulin inhibits glycogenolysis and gluconeogenesis (stops glucose production)
Muscle and adipose tissue: insulin increases glucose transport into muscles and then is used for glycolysis.
What happens to glucose?
50% used for energy (ATP production), 5% becomes glycogen and 45% is stored as fat. Glycogen is available for immediate glucose need and fat is for slower needs.
How big is the fat store and what is it used for?
20-30% of body weight but 70-80% of the stored energy.
Adipocytes are hormonally active to produce hormones, such as adipnectin, resistin, leptin, and TNF-alpha.
Lipolysis produces free fatty acids, which are oxidised to ketone bodies, which can be utilized as energy.
And glycerol - transported to the liver for krebs cycle.
How is excess carbohydrates stored?
Excess carbohydrate is stored as glycogen (75% in muscle and 25% in the liver).
