Integration of Metabolism Flashcards
What stimulates insulin secretion?
- rise in blood glucose
- rise in amino acid concentration
- gut hormones (secretin)
- glucagon
What inhibits insulin secretion?
Adrenaline
How is insulin secretion controlled?
Glucose enters beta-cell via GLUT2 receptor. Enters TCA cycle and releases ATP.
ATP blocks K+ channel - changes membrane potential of beta-cell.
Causes Ca2+ channels to open - influx of Ca2+ into cell, stimulates release of insulin in vesicles.
What stimulates glucagon secretion?
- low blood glucose
- high concentration amino acids in blood
- adrenaline
What are the metabolic effects of insulin? (general)
- promotes fuel storage
- stimualtes glycogen synthesis and storage.
- stimulates fatty acid synthesis and storage from carbohydrates
- stimulates amino acid uptake and protein synthesis
What are the metabolic effects of insulin at a molecule level?
- Activation of Akt protein kinase.
1. Insulin binds - autophosphrylation of receptor
2. Phosphorylation of IRS 1/2
3. IRS 1/2 sctivates P13 kinase > kinase cascade
4. Activation of PDK 1 kinase by PIP3.
5. Triggers phosphorylation activation of phosphokinase B.
By what mechanism does insulin cause gycogen synthesis?
Activated Akt/PkB
- Phosphorylates glycogen synthase kinase (inactivated).
- Glycogen synthase remain active - catalyses glycogen synthesis.
Akt triggers GLUT4 receptors to fuse to membrane to increase glucose uptake into muscle cells.
By what mechanism is lipolysis inhibited by insulin?
Active Akt phosphorylates phosphodiesterase (ACTIVE)
cAMP converted to ATP - inactivation of protein kinaseA so hormone sensitive lipase is not activate by protein kinase A.
By what mechanism does insulin effect gene expression?
Through Ras and MAPK.
Autophosphorylation of insulin receptor - pathway occurs through Ras. Cascade of phosphorylation up to MAPKinase.
MAPK will activate/inhibit gene expression of different genes.
Which GLUT transporters are found in different tissues?
GLUT1 - Erythrocytes and brain (high affinity)
GLUT2 - Liver and beta-cells (non-dependent - low affinity)
GLUT3 - Neurons (high affinity)
GLUT4 - Adipose , Muscle (insulin dependent - low affinity)
What are the metabolic effects of glucagon?
- mobilise fuel
- activates glyconeogensis in the liver
- activates glycogenolysis in the liver
- promotes fatty acid release from adipose tissue
- promotes fatty acid oxidation and ketone body formation in the liver.
What are the metabolic effects of adrenaline?
- inhibits insulin secretion
- stimulates glucagon secretion
- Stimulates gluconeogenesis in muscle and liver
- stimulates fatty acid release from adipose tissue
What are the metabolic effects of cortisol?
- provides long term requirements
- stimulates amino acid metabolism from muscle (catabolism)
- stimulates gluconeogensis
- stimulates fatty acid release from adipose tissue.
Which tissue(s) have priority for glucose?
Erythrocyte and the brain.
Brain can only use glucose as fuel source.
Erythrocyte can only use glucose as there is no mitochondria
What happens to excess glucose in the liver?
Glucose > acetyl CoA > TAG
TAG is transported in VLDL to adipocytes.
What occurs during fasting?
Hormone sensitive lipase is activated by glucagon and adrenaline.
Fatty acids are transported to the liver bound to albumin.
Why is fatty acid not a gluconeogenic precursoe?
Pruvate > acetyl CoA is IRREVERSIBLE
Catalysed by pyruvate dehydrogenase.
PDH is activated by insulin and inhibited by insulin.
How do ketone bodies form?
Fatty acid oxidation in hepatocyte - leads to high concentration of acetyl CoA - exceeds TCA capacity.
Excess are channelled into into ketone body formation.
Name 2 ketone bodies.
Acetoacetate
B-hydroxybutarate
What is the general function of ketone bodies?
Most tissue use glucose and ketone bodies as energy sources.
Ketone bodies cannot be used by erythrocytes and are only used by the brain if necessary.
What metabolic pathways occur in prolonged starvation?
Body utilises more ketone bodies.
More KB are recovered from the kidney.
Inhibits breakdown of amino acids/muscle.
What are the specific functions of ketone bodies?
- act on the pancreas to stimualte insulin release
- limits muscle proteolysis
- limits adipose tissue lipolysis
What is diabetes mellitus?
Unable to regulate blood glucose concentration. Can be type 1 or type 2.
What is type 1 dibetes?
Autoimmune destruction of Beta-cells in the pancreas.
Body cannot produce insulin to regulate blood glucose.
What are symptoms of type 1 diabetes?
Polyuria, polydipsia Excess eating fatigue weight loss muscle wasting weakness
How is type 1 diabetes managed?
Chronic condition.
Monitoring of blood glucose levels and injecting with insulin when required.
What causes type 2 diabetes?
Associated with diet and lifestyle e.g. obesity.
Which type of diabetes has hyperglaecemia or ketoacidosis?
Type 1 = hyperglaecemia and ketoacidosis
Type 2 = hyperglaecemia but NO ketoacidosis
How is type 2 treated?
Often responds to diet and oral hypoglaecemic agents.
What is the difference between untreated diabetes mellitus and starvation?
In starvation, ketone body production stimulates insulin release which limits muscle breakdown.
In diabetes theres no insulin to be released so muscle breakdown continues hence muscle wasting occurs.
Name 4 chronic complications of diabetes mellitus.
Microangiopathy - changes in walls of small blood vessels.
Retinopathy - blindness is 25x more common in diabetics.
Nephropathy - renal failure 17x more common in diabetics
Neuropathy - postural hypertnesion, impotence, foot ulcers.
