Carbohydrate metabolism and blood glucose control Flashcards
Explain Carbohydrate Metabolism
1- Dietary sugar and starch ingested are transformed to fructose, galactose and glucose
2- metabolized in liver
3- then used via glycolysis & TCA cycle to generate energy
what happens in the case of no glucose in body from food
Glucose can be synthesized through fat or amino acids , if there is no glucose available to use
How does the liver convert fructose and galactose to glucose ?
Why must it be converted ?
- the enzyme glucose 6-phosphatase , which hepatocytes contain in large amounts converts them to glucose
- glucose is the final pathway for carbs to be transported into tissue cells
How does glucose transport through the cell membrane
- Glucose is transported by facilitated diffusion across the cell membrane
- this involves protein transporters binding with glucose to move it across the membrane
What are GLUT proteins, what is the difference between the types and what is their function
- glucose transporters that mediate the concentration of glucose uptake in tissues
- some are more efficient than others, those are often found in tissue that requires a lot of energy ( ex: brain , RBC, cornea, CNS ) GLUT 1&3 > GLUT 2&4
How is glucose absorption in GI different
requires active sodium-glucose co-transport
What is the main regulator of glucose concentration
Insulin
Describe Insulin, why it is secreted and it’s degradation
- large polypeptide hormone of 2 amino acid chains
- produced by pancreatic B-cells in islets of langerhans
- secretion is stimulated by increase of blood glucose levels
- degraded in liver after 6 min
How is insulin secreted
- high levels of ATP close potassium channels in Beta cell
- membrane depolarization opens Calcium channels
- calcium is insulin secretion signal
- preformed insulin is produced by ER , gets processed through Golgi and then insulin is released into blood stream
What are Sulfonylureas
drugs used to treat type 2 diabetes , close potassium channels to increase insulin secretion
what is Glucagon-like peptide
drug that increases insulin secretion by opening calcium channels
What is the effect of Somatostatin and Norepinephrine on Insulin
reduce insulin secretion
When are insulin levels highest , how long does it last
after a meal , 2-3 hours
Graph relationship with insulin secretion and glucose
linear relation
Minor factors regulating insulin secretion
- levels of circulating amino acids in blood: can stimulate insulin which increases protein tissue uptake
- GI hormones : while eating
- Autonomic nervous system: stress decreases secretion , eating / relaxing increases secretion
Effect of insulin on adipose tissue
increase glucose uptake = lipogenesis ( store fat) decrease lipolysis ( breakdown of fat )
Effect of High insulin on liver
Increase glucokinase and thus glucose uptake
increase glycogen synthesis , storing glycogen
decrease gluconeogenesis ( break down of glucose)
Effect of insulin on striated muscle
increase glucose uptake, glycogen synthesis, protein synthesis
Effect of Insulin on glucose facilitated diffusion
- in fasting conditions : muscle GLUT4 does not take up glucose at low levels, will use fat instead
- GLUT4 in insulin presence will increase glucose uptake , increasing facilitated diffusion
Exercise effect on Glucose facilitated diffusion
muscles active = glucose diffused to be used for energy
muscles inactive = glucose turned to glycogen
Effect of low insulin on liver
- increase glycogen phosphorylase which increases glycogen breakdown
- increase glucose 6 phosphatase which increase glucose release from liver
Effect of insulin on Brain
- Insulin has minimal effect on brain glucose uptake
- GLUT 1 is always readily taking up glucose
What happens due to hypoglycaemia ( symptoms )
nervous irritability, fainting, convulsions , coma
What is the major site of glucose uptake
muscle
If Boy suffering from hyperglycaemia is given insulin and potassium chloride , what will the rapid effect of insulin stimulate
Glucose transport in muscle
What raises glucose levels ( 4 hormones )
1- glucagon
2- adrenaline/noradrenaline
3- Growth hormone
4- cortisol
What is Glucagon , what stimulates its secretion, what does it counteract
- large polypeptide produces by pancreatic alpha cells in islets of langerhans
- stimulated by low blood glucose
- counteract actions of insulin
Effect of low blood glucose in liver
- increase glycogenolysis to produce more glucose
- increase gluconeogenesis
- decrease glycogen storage
Explain how glycogen breaks down into glucose
- glucagon receptor signalling increases cyclic AMP and Protein kinase
- stimulating glycogen phosphorylase
promoting glycogen breakdown and glucose release
How is glucagon secretion regulated ( stimulation / inhibition )
- increased by low blood glucose and increased amino acids ( lead to gluconeogenesis )
- exercise increases glucagon secretion
- inhibited by somatostatin produced by pancreatic delta cells
Describe somatostatin mode of action
general suppressive action on metabolism thus extending time nutrients are used
Effect of adrenaline/noradrenaline on glucose metabolism ( in liver and adipose tissue )
increases glycogenolysis & lipolysis
Effect of Cortisol and Growth hormone on glucose metabolism ( in liver, muscle and adipose tissue )
stimulates gluconeogenesis, decreases tissue glucose uptake and increases lipolysis
Relationship of hypoglycaemia and stress
stress hormones will increase blood glucose levels to prevent hypoglycaemia
Explain Type 1 diabetes, cause, onset and its frequency
- caused by B-cell dysfunction in pancreas
- due to viral infection, hereditary or autoimmune disease
- insulin-dependent
- 10% of cases
- juvenile onset ( 14 y)
Explain Type 2 diabetes, cause, onset and its frequency
- tissues become resistant to insulin
- non insulin dependent
- obesity related
- adult onset ( 30y)
Hyperglycaemia symptoms ( 8)
- always hungry
- tiredness
- frequent urination.
- sudden weight loss
- wounds not healing
- blurry vision
- numb feet or hands
- thirsty
Glucose filteration in kidneys
glucose is filtered out & reabsorbed in proximal tubule using GLUT2
Effect of hyperglycaemia on urine
if blood glucose is at a higher concentration than 10 mmol/L the proximal tubule is overwhelmed and glucose will be excreted in urine
What are Gliflozins
drugs that decrease renal glucose reabsorption and thus decrease blood glucose levels
How does hyperglycaemia cause dehydration ( Explain effect in cells, kidney & brain )
- high blood glucose increases osmolarity of ECF and thus cells loose water
- high blood glucose increases osmolarity in renal tubular fluid decreasing water absorption and thus water is excessively lost in urine
- increased blood osmolarity activates osmoreceptors to secrete ADH and activate the hypothalamus
What is glucotoxicity and its effect
high concentration of glucose will cause glucose to react with proteins and signalling pathways which can result in tissue damage
Diabetes effect on fat metabolism ( 2 possible conditions)
- increased lipase increases lipolysis ( since insulin is what usually inhibits lipase )
- fatty acids will be metabolized to keto acids which decrease blood PH = diabetic keto acidosis ( can be smelled on breath )
- can also cause hyperkaelemia
Effect of diabetes on body protein
- decrease insulin increases protein and fat use and thus rapid weight loss
- especially type 1 diabetes
How is Diabetes diagnosed
1- Urinary glucose level ( over 10 mmol/L)
2- Fasting blood glucose
3- Fasting plasma insulin ( different for T1 &T2 diabetes)
4- Glucose tolerance test ( if blood glucose is not decreased after glucose is given )
5- keto acidosis ( nail varnish smell on breath )
If someone is severely hypoglycaemic what additional condition might occur
keto acidosis since the hypoglycaemia will decrease insulin levels and increase glucagon
