Selected Hormonal Issues Relating to Exercise and Substrate Use

ATP used up by muscle contraction can be regenerated through 4 processes: 1-MK2-CPK 3-Glycolysis4-Oxidative Phosphorylation... With processes #3 & #4 being dependent on availability of glucose, fatty acids, and amino acids... Remember This Stuff???

Tissue Stores ~g ~ Days ~ Days ~ Minutes StarvationWalkingMarathon Running Adipose TG - all 9, ,018 muscles ~ kg muscles = 140g – 420 g 0.25 – Liver Glycogen Muscle Glycogen Blood Glucose We now need to look at estimates of body “stores” of energy substrates

Regulation of glucose levels in the blood is very important Normal Fasting (Serum) ~ 70 – 100 mg/dl Elevated = Diabetes Low = Hypoglycemia Insulin from pancreas stimulates uptake of glucose into muscle cells by activating the GLUT4 transporter. When serum levels of glucose decrease too much, then the pancreas releases glucagon to stimulate the liver and kidney to break down glycogen to glucose and release glucose into the blood (glycogenolysis). Adrenals will release cortisol if levels stay too low to enhance breakdown of protein in muscles to release amino acids so the liver can pick up the amino acids and make them into glucose (gluconeogenesis).

Insulin binds to the insulin receptor which then activates a series of phosphorylase & protein- protein enzyme reactions ending up with the translocation of the GLUT4 protein to the cell membrane.

Because the energy needs of the cells have not changed all that much after a meal, most of the additional uptake of glucose is handled in the storage pathways while some is metabolized at the expense of FFA Notice that at rest FFA provide the majority of the cells energy requirements... and insulin can greatly increase uptake of glucose into the cell...

At rest, epinephrine can activate glycogen and TG breakdown in muscles... it is important to note that P’ase b also can be activated by calcium and by ADP... AND... that Triglyceride Lipase, aka hormone sensitive lipase, can be activated by PKC and ERK. In the liver and kidney, glucagon will bind to the glucagon receptors & activate PKA to enhance glycogen breakdown in these tissues for export to the blood and FFA metabolism to inhibit glycolysis... (or glucagon binding to the glucagon receptor)

Growth hormone is released in large quantities during prolonged periods of fast growth, such as during early childhood and adolescence. Stressful exercise also stimulates a transient increase in release of GH. Note that GH “directly” activates STAT, PLC, IRS1&2 and SOS/Grb-2. In addition, both typical PKC (via IP3 and DAG) and atypical PKC (via PDK-1) are activated. These effects result in the activation of an array of promoter molecules as well as glucose uptake and TG breakdown.

Muscle contraction can activate glucose transport independent of insulin and activate TG breakdown independent of epinephrine, greatly increasing glucose uptake and FFA availability... As a result of muscle contraction, all metabolic pathways of ATP generation increase while those of storage and synthesis decrease... Because the glycolysis pathway increases so much faster than the others, glycogen stores in the muscle will decrease very quickly compared to TG stores...

Moderately stressful exercise: As a result of continuous muscle contraction, all metabolic pathways of ATP generation increase while those of storage and synthesis decrease... Because the glycolysis pathway increases so much faster than the others, glycogen stores in the muscle will decrease more quickly than TG stores... increasing the dependence of muscles on plasma supplies of substrates... a hormonal issue...

- Time to exhaustion: ~ hours

Subjective feelings of fatigue appear to coincide with an increase in glucagon and cortisol levels. These increased glucogenic hormones are often associated with a decline in serum glucose - resulting predominantly from glycogen depletion in the liver (and muscles) or associated with stress; resulting from anything that induces a state of anxiety or tension (such as being sore?... tired?... annoyed?) Declining glycogen stores means a greater reliance on the less efficient fuel: FFA (you have to slow down). Consuming carbohydrate during exercise should blunt the endocrine response as well as delay fatigue...

-Time to exhaustion: ~ 2.3 – 3.3 hours

One more endocrine issue is the effect of repeated exercise on the endocrine response to acute exercise.