1. 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).

2. 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.

3. 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.

4. Growth hormone is released in large quantities during prolonged periods of fast growth, such as during 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.

5. ERK-MAPK - p38 MAPK - JNK-MAPK - PI3K/Akt The major signal transduction pathways (STPs) involved in regulating the growth and development of cells are the ERK-MAPK, p38-MAPK, JNK-Mapk, PI3K/Akt, and the “Nfκβ” pathways. These STPs regulate synthesis of the many proteins that are necessary for maintaining and enhancing cell function.

6. Regulation of Signal Transduction (S-T) Pathways Activities of S-T pathways are regulated by a variety of growth factors, hormones, calcium, and ROS. Note that both Calcium and ROS affect enzymes that activate S- T pathways. Thus control of Calcium and of ROS are very important for controlling S-T. Exercise stress will activate several signal transduction pathways through calcium, oxygen-radical, and NO mediated activation of PKC, PKCζ/λ, and PKG, resulting in the transient activation of a variety of promoters.

7. Activation of the growth hormone pathway by exercise will result in proliferation of satellite cells and fusion of the satellite cells with existing muscle cells.

8. Activation of IGF1 synthesis by muscle contraction leads to autocrine activation of IGF receptors and activation of PI3K and ultimately Akt, ERK-MAPK, and phospholipase D. The coordinated removal of mTOR inhibition by TSC1/2, FOXO and activation by phosphatidic Acid Along with activation of MAPKs enhances protein synthesis

9. Activation of the calcineurin pathway by neural stimulation will result in expression of contractile and oxidative function related proteins.

10. Activation of a variety of metabolic stress-related pathways will lead to the coordinated activation of transcription of both nuclear and mitochondrial genes.

12. Activation of a variety of metabolic stress-related pathways also leads to the activation of antioxidant enzyme genes.