HGH/IGF-1 [PITUITARY LIVER AXIS] (carbohydrate\caloric restriction or fasting; sulfur is released to form a type of insulin IGF-1 from the liver not the pancreas thus suppressing/disabling pancreatic insulin)===>
[OFF switch?]===>{mTOR}<===[ON switch?]
Or is it the opposite[3]? (+ - variable dependent on certain factors)
[ON switch?]===>{mTOR}<===[OFF switch?]
<===GLUCAGON [PANCREAS & GLUCAGON A CELLS IN STOMACH LINING] (i.e. eating protein)
Sugar or excessive glucose blocks the ability of HGH (pituitary) and IGF-1 (hepatic) to function even if it is abundant in the body. Thus lowering DHEA levels from the hypothalamus?
Eating protein and fasting is the mTORC1 ON/OFF switch?
Glucose, ketones and free fatty acids all inhibit glucagon release[5]? (catabolism?)
Amino acids stimulate glucagon release and uptake into the liver, covalent phosphorylation initiated by glucagon activates the former and inhibits the latter[6]?
References:
[1] “…Cumulative evidence supports the hypothesis that mTOR acts as a master switch of cellular catabolism and anabolism. …”…More
[2] “…Mechanistically, mTORC1 facilitates the switch towards anabolic metabolism that is required for T-cell activation and expansion …” …More
[3] “…The important control functions of the mTor kinase influence cell metabolism, division and growth. For example, the molecular control unit ensures the production of new proteins or the storage of fat and carbohydrates in metabolically active tissue. These processes are stimulated by the influx of sugar and amino acids and by signals initiated by growth factors including the insulin-like growth factor. If this influx does not occur in a starvation period, mTor switches the cell from anabolic to catabolic mode. Instead of synthesizing new proteins from amino acids, the cell now activates clean-up processes to remove damaged proteins, which could become hazardous for the cell or organ. The cleansing effect of interval fasting is attributed to the consequences of deactivating the mTor kinase. In certain disease states, it would be sensible to shut down the mTor kinase complex. In cases of diabetes and obesity for example, pathological mutations exist in the cellular control center. This also applies to many cancers. This raises the question how and where to switch off such a complex mechanism. A Surprising Discovery: To find this switch-off mechanism, researchers in the Leibniz–Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin kept a keen eye on nature’s ways to accomplish this down regulation. According to known facts, the lysosomal mTor kinase complex becomes less active or inactive in extended hunger periods. The lysosome is the regular cell compartment for the mTor kinase complex activity. However, the complex also turns inactive several times during the day without leaving its membrane-bound place. This happens for example when the stimulating insulin signals do not arrive. Therefore, there has to be a natural mTor brake somewhere in this location. The discovery of this brake is now published in the top journal ‘Science’. It came as a surprise even for FMP Director Professor Volker Haucke: "We found a local lipid kinase on the lysosome. This kinase deactivates mTor. Paradoxically, if the lipid product of this kinase is synthesized on the cell surface membrane, it is rather known as growth stimulating lipid, i.e. it has the exact opposite effect." …” …More
[4] “…However, recently, we have identified another mechanism by which AKT is activated; in the presence of rapamycin we found hyperphosphorylation of IGF-1R due to increased secretion of IGF’s (Kurmasheva and Houghton, unpublished data). IGF’s are potent survival factors, inhibiting the activity of pro-apoptotic proteins such as Bad through phosphorylation and sequestration with 14-3-3 proteins (10). Anti-apoptotic IGF-1R signaling may be either AKT-dependent or independent. Thus, there is reason to consider blocking IGF-1R signaling in the context of mTORC1 inhibition. We have previously shown that in the absence of exogenous IGF’s rapamycin induced apoptosis in cancer cells that are deficient or mutant for TP53, whereas cells with functional TP53 remained viable (11, 12). IGF’s rescued from rapamycin through a PI3K-dependent, AKT-independent pathway (13). …” …More
[5] “…With longer stimulation, glucagon action at the liver results in a glucose-sparing activation of free fatty…” …More
[6] “…Glucagon activation of phosphorylase is in some way antagonized by insulin … Activation of glycogen phosphorylase is an example of covalent …” …More
Brian started just making a food documentary. Over the 30 some episodes how he changes and what he believes mirrors must of us.