Exercise and Glycaemic Control W10 Flashcards
What 3 key steps does exercise increase the uptake of glucose?
1) Delivery
2) Transport across the muscle membrane
3) Intracellular flux through metabolic processes
- Glycolysis
- Glucose Oxidation
What is deoxy glucose?
Glucose molecule that cannot be metabolised (cannot enter glycolysis)
The molecule just accumulates in the cell for a marker of glucose uptake
Can glucose uptake occur if there is no insulin signalling?
Yes
When does GLUT4 return back to its inactive position after exercise?
2 hours (CHO golden window)
What does an enzyme end in “kinase” do?
Phosphorylates
What is AMP activated kinase activated by?
AMP
What activates enzymes in an exercising muscle?
ATP is converted to ADP and AMP
What activates AMP?
Transient fluxes in Ca
What is AICAR converted into?
ZMP
What is ZMP?
Tricks cell into thinking AMP is leaving the body= causes AMP to be activated
When does an insulin receptor become phosphorylated?
When it is exposed to insulin on the outside
What does phosphorylation of insulin receptor cause?
Leads to phosphorylation cascades that ultimately lead to GLUT4 being translocated up onto membrane
What does the Rab-GTP protein do?
Allows translocation to the membrane
Prevents the conversion of Rab-GTP to Rab-GDP
What is the state of “Rab” protein influenced by?
Protein TBC1D4
Where is GLUT4 active position?
Membrane
How does GLUT4 translocate?
It attaches onto a little cytoskeleton which moves the protein up the membrane
What does Protein TBC1D4 drive in Rab in its unphosphorylated form?
Drives it into its GDP form
What does Protein TBC1D4 drive in Rab in its phosphorylated form?
Drives it into its GTP form
What is Protein TBC1D4 phosphorylated by?
Insulin
AKT
What are the effects of a single exercise bout on glycaemic control?
Increased perfusion of active muscle exposure to target tissue
Translocation of GLUT4 to cell membrane
Sensitisation of insulin response
Increased expression of GLUT4 gene
Increased glycogen synthase activity
What is sensitisation of insulin response?
Phosphorylation of TBC1D4
What is translocation of GLUT4 to cell membrane regulated by?
Intracellular calcium
AMPK
Nitric Oxide
How can exercise training alter glycaemic control?
1) Delivery of glucose and insulin to the muscle
2) Insulin
3) Amount of GLUT4
4) Glycogen Synthase activity
Why do type 2 diabetic individuals have an inability to accept fat?
In type 2 diabetes, there is more of the fat transporter CD36 up on the membrane and less of it in the inside of the cell
Results in muscle increasingly likely to accept fat
(This causes more TAG stores inside the muscle)
What is mitochondrial biogenesis?
Production of new and potentially bigger mitochondria
When a peak is activated, what can it stimulate?
AMP
Ca
What does the stimulation of Ca cause?
Activates AMP
What happens when PGC-1alpha is switched on?
Stimulates production of new mitochondria (mitochondrial biogenesis)
What is AMPK influence on fatty acid oxidation in muscle?
Increases fatty acid oxidation
What inhibits the transport of fat into the mitochondria?
Malonyl-CoA
What do type 2 diabetic individuals see in the metabolic paradox?
See large stores of intramuscular triglycerides due to inactivity (turnover of these stores are minimal)
See lipid derivates to be produced (interferes with the insulin seeking cascade)
What is AMPK primary factor?
Improves insulin sensitivity
What does activated PGC1alpha do?
Produce more mitochondria
What does AMPK does?
Increase the amount of GLUT4 produced in the muscle
It translocate GLUT4 to the active position to stimulate it
What does the ACC enzyme do?
Reduces amount of malonyl-CoA
What are the effects of training on glycaemic control?
Muscle hypertrophy
Less inhibition of insulin-induced capillary perfusion
Muscle capillary density
Increased insulin signalling
Reduced intramuscular concentration of fat moieties (DAG) and inhibition of tyrosine phosphorylation
Increased TBC1D4 (and phosphorylation) with regular activity
Increased mRNA and protein of GLUT4 transporter
Increased enzymes of glucose storage and oxidation
Why may increased insulin signalling occur?
May be due to reduced adiposity and changes in circulating adipocytokines
