Metabolic system Flashcards
How do pancreatic beta cells sense too much glucose.
Sulfonylurea drugs utilize this
Glucose will bind to GLUT2 channels. Then it is phosphorylated by glucokinase. Once phosphorylated it can’t leave the cell. It undergoes glycolysis and TCA to make ATP.
The ATP inhibits ATP dependent potassium channel and prevents potassium from leaving the cell. THis depolarizes the cell.
The depolarization activates voltage dependent calcium channel leading to calcium influx.
Calcium triggers the exocytosis of insulin.
Sulfonylurea drugs block potassium channels like ATP to promote insulin secretion.
Describe the utilization of glucose during digestion involving the
- liver
- skeletal muscle
- adipose tissue
- brain
Liver (GLUT2)
Brain (GLUT3)
Skeletal muscle (GLUT4)
Adipose tissue (GLUT4)
—–digestion———————–
Liver (GLUT2) takes up glucose, breaks it down into ATP. Whatever isn’t used is stored as glycogen. Very little is stored as tags (nonalcoholic fatty liver disease)
Skeletal muscle (GLUT4) glucose not captured by liver goes here, only movement will enhance muscle ability to use up glucose. It will make ATP but skeletal muscle is also a large storehouse for glycogen. Little TAGs
Brain (GLUT3): makes almost no fat, takes the glucose and makes energy
Adipose (GLUT4): Glucose (insulin enhances this) is taken into adipose tissue and now most of it is converted into TAGs. Insulin also increases LPL activity releasing more fatty acyl coA from chylomicrons which is converted into tags.
Describe the utilization of glucose during fasting involving the
- liver
- skeletal muscle
- adipose tissue
- brain
Liver (GLUT2) Brain (GLUT3) Skeletal muscle (GLUT4) Adipose tissue (GLUT4) -insulin activity goes down, glucagon activity increases
- glycogen synthesis is inhibited, glycogenolysis increases,
- gluconeogenic enzymes are increased (primary pathway of hepatic glucose production)
- lipogenesis is inhibited (breakdown of fat!), FFA is transported to liver to make ketone bodies used by brain.
—–digestion———————–
Liver ; (from skeletal muscle): lactate, amino acids, and (from adipose tissue): glycerol and FFAs are used to make glucose, ATP and ketone bodies. Glucose will leave via GLUT2.
Skeletal muscle: glucose cannot leave the skeletal muscle because it lacks phosphatase. Instead glucose is used to produce lactate which can be transported and once it gets to liver is made into glucose. Epinephrine and norepinephrine signal proteolysis which allows amino acids to be used for glucose/ketone bodies.
Brain (GLUT3): still keeps taking glucose and ketone bodies to make ATP and survive
Adipose: breaks down TAGs into glycerol and fatty acids. Glycerol is used to make glucose and fatty acids can be used to make ATP and ketone bodies.
Describe the way insulin deficiency/resistance causes artherosclerosis and ketosis?
It all boils down to that the lack of insulin promotes lipase, increasing fatty acids and glycerol in the blood.
Excess FA in plasma promotes liver conversion into lipoproteins. This will increase risk of atherosclerosis.
Fatty acid will also be converted into ketone bodies.
Growth hormone in context of blood glucose
How about thyroid hormone?
Growth hormone tries to increase blood glucose levels by inhibiting glucose uptake. Unlike cortisol it is an anabolic hormone.
Increases skeletal muscle production and breaks down fat.
Thyroid hormone:
increases glucose output by liver, breaks down protein, breaks down fat, increases insulin clearance by liver .
Describe these two counter regulatory nutrient sensing pathways
AMPK
mTOR
AMPK - senses low ATP levels and its primary goal is to increase ATP levels.
-it will stimulate catabolic pathways that generate ATP and inhibit anabolic pathways that consume ATP
mTOR/Akt: senses amino acid availability, regulates cell growth and cell proliferation, so when there is enough nutrients it promotes anabolic pathways. (lipid, nucleotide, nutrient uptake), is promoted by insulin. (this pathway is actually why insulin increases glucose uptake, glycogen synthesis and protein synthesis)
