Biochemistry - Insulin and Glucagon Flashcards
Blood glucose, insulin and glucagon levels after a high carbohydrate meal
- Glucose levels begin low and quickly increase and then will slowly drop back down
- Insulin level will begin low and spike again before dropping
- Glucagon levels will start high and drop rapidly before increases after around 180 mins
Glucagon
- Secreted in endocrine pancreatic Alpha cells
- Produced in response to low blood sugar levels
- 29aa polypeptide
- Stops glycogen synthesis
- Stimulates glycogen breakdown in liver to glucose which can go into the blood
Isuliun
- Secreted in endocrine pancreatic Beta cells
- Produced in response to high blood sugar levels
- 51 aa polypeptide
- Stimulates all body cells except brain cells to take up glucose and begin glycogen synthesis
- Insulin is a growth hormone, promotes fat deposition
Glucose transporters
- GLUT1 is highly conceived and has high affinity for glucose
- GLUT2 is found in beta-cells, liver and gut and has a low affinity for glucose
How does glucose trigger insulin release?
- Glucose binds to a glucose transporter and enters the cell beginning respiration
- ATP is produced
- ATP binds to a ATP sensitive K+ channel depolarising the cell (Ca2+ influx)
- This stimulates vesicles containing insulin to burst and move into the blood
- Arginine also triggers this pathway
Glycogenolysis
Glycogen breakdown is regulated by the hormone Glucagon
Glyconeogenesis
Formation of glycogen is regulated by the hormone insulin
Insulin mediated glucose uptake
- Insulin binds to the insulin receptor on the outside of the cell membrane
- PI-3K and IRS1 bind to the insulin receptor on the inside of the cell membrane
- This stimulates the movement of the Glucose Transporter to the cell membrane
- Glucose can now move through this transporter into the cell
Diabetes Mellitus
Typically hyperglycaemic- excess glucose in blood appears in urine.
- Fasting glucose is >11mM
- Capillaries and veins get damaged and most diabetic die from heart failure
- Nephropathy (kidney failure)
Diabetes Mellitus
Typically hyperglycaemic- excess glucose in blood appears in urine.
- Fasting glucose is >11mM
- Capillaries and veins get damaged and most diabetic die from heart failure
- Nephropathy (kidney failure)
- Retinopathy
- Bad peripheral circulation
- Elevated glucose results in uncontrolled uptake in epithelial cells and blood vessels
HbA1c
- Alpha chain of haemoglobin will bind glucose
- Can follow amount and see if people are monitoring glucose correctly
Type 1 Diabetes
- Insulin dependants
- Common in juveniles - autoimmune disorder
- Viral infection can trigger in adults
- Loss of beta cells so cannot produce insulin
- Treat with insulin injections
Type 2 Diabetes
- Non-insulin dependant, insulin insensitive i.e. cells do not respond to insulin
- Common in older people (90%) along with obesity and stress
- Variable insulin levels, start high and then drop
- After a while will stop producing insulin
What can prevent uptake of glucose into cells
- High fat content of the blood may alter signalling/glucose metabolism
- Need more and more insulin in insulin insensitive people - body cannot keep with demand
- If mitochondria are overactive they will produce free radicals which in turn will shut off the glucose transporter
- Thus blood glucose levels rise
- Mitochondrial DNA mutations can also impair glucose uptake
Fuel Choice During Starvation
- Glucose in the blood
- Glycogen stores
- Use proteins for gluconeogenesis (from 2 days)
- Creates large amounts of ketone bodies acidifying the blood
Ketone Bodies
- brain cannot use fats
- from 3 days of starvation, 30% of the brains energy is from ketone bodies
- After 40 days it is 70%
- Use results in ketoacidosis
Ketoacidosis
- Untreated type 1 diabetics
- Starving
- Binge drinking alcoholics
ATP use in muscles
- When ATP is used it is replaces almost immediately through creatine phosphate
- If ATP stores declined cells dies by necrosis
Fuel Use During Exercise
- Muscle glycogen
- Blood borne glucose
- Blood borne fatty acids
Fuel Sources for Muscle Contraction
- Creatine phosphate has the fastest rate of ATP production but produces little
- Fatty acids (adipose) have the slowest rate of ATP production but produce a lot of it