Hogyan árthatsz magadnak covid hullámok esetén?
A válasz egyszerű: magas inzulinszinttel.
A magas inzulinszint növeli zsírsejtjeidben a GRP78 fehérje mennyiségét, amely elősegíti a covid-19 vírus fertőzőképességét, szaporodását, gyors terjedését a szervezetben, növeli a gyulladásszintedet, elősegíti a citokin vihart.
(1) A tüskefehérje bejutását is elősegíti a sejtekbe, a szív és más létfontosságú szervek körül, úgyhogy ezért is jók lehetnek az oltások magas inzulinszintnél. (ez irónia)
A kulcs tehát az inzulin szinted és gyulladásod csökkentése. A magas inzulinszintet az inzulin rezisztencia, diabetes, magasabb életkor és túlsúly okozza. Az inzulin termelést egyébként az “éhséghormon” , a ghrelin csökkentheti, de a ghrelin a GRP78 túlzott mennyiségét is csökkentheti.
(2) Mivel a ghrelin elősegítheti a covid tüneteid csökkenését, ezért javasolják is covid terápia céljából, hiszen gyulladásgátló és antioxidáns hatása is van.
(3) Ha sohasem laksz teljesen jól, hanem mindig érzed, hogy éhes vagy, akkor akár 3x os ghrelin-szinted is lehet a jóllakottsághoz képest és ezzel nagyon nagyon jót teszel magadnak, jelentősen növelheted túlélési esélyeid és hosszabb ideig fogsz élni, persze csak akkor, ha nem vagy csontsovány, mert akkor annyit ehetsz, amennyi jólesik. Túlsúlynál kevesebb ghrelint termel a szervezet (gyomor, hasnyálmirigy és valamennyit az agy is).
Ezért aztán nagy a veszélye annak, hogy a ghrelin peptid kiejtését is betiltja Magyarország új “gyógyászati szaktekintélye”, a GVH. Utána minek nevezzük? ”Ne lakj jól!” peptidnek?
Egyébként a tudjukmi is csökkenti az inzulin szükségletet, ezt több klinikai vizsgálatban is látták, de ezt kiegészítheted még azzal is, hogy nem eszed soha degeszre magad, mert abba könnyen belehalhatsz, vagy ha azt nem is, károsodhat tőle az agyad. (4)
1- Shin J, Toyoda S, Nishitani S, et al. Possible Involvement of Adipose Tissue in Patients With Older Age, Obesity, and Diabetes With SARS-CoV-2 Infection (COVID-19) via GRP78 (BIP/HSPA5): Significance of Hyperinsulinemia Management in COVID-19. Diabetes. 2021;70(12):2745-2755. doi:10.2337/db20-1094
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660985/ , In patients with older age, obesity, and diabetes, hyperinsulinemia causes adipose cellular stress and induces the XBP-1-mediated overexpression of GRP78, which may increase its localization to the cell surface and circulation (23,24,39,40). The high expression of GRP78 might aggravate viral infection, spread, replication, and inflammatory response as a binding partner of the SARS-CoV-2 spike protein and ACE2, which possibly contributes to the severe progression and outcome of COVID-19 in patients with older age, obesity, and diabetes (Fig. 5).
Insulin treatment significantly increased the protein expression of GRP78 in a dose-dependent manner in 3T3-L1 adipocytes (Fig. 3C). Increasing glucose concentrations in the culture media from 5.5 mmol/L (99 mg/dL) to 25 mmol/L (450 mg/dL) had no effect on the protein expression of GRP78
these results suggested that hyperinsulinemia induced the overexpression of GRP78 in adipocytes,
Binding of SARS-CoV-2 to cell surface GRP78 or the related stimuli could activate the NF-κB or JNK/STAT3 transcriptional pathway and induce cellular inflammatory responses. SARS-CoV-2 potentially exploits ER-located GRP78 as a molecular chaperone to produce and assemble viral particles, which enables successful viral replication (brown-colored virus indicates newly replicated SARS-CoV-2). The high expression of GRP78 in patients with older age, obesity, and diabetes may contribute to the severe progression and outcome of COVID-19.
Importantly, we found that soluble GRP78, a mimetic of the circulating form, can facilitate the accumulation of SARS-CoV-2 spike protein in lung epithelial cells in vitro (Fig. 1E). These results suggest that soluble GRP78 in circulation, possibly from adipose tissue, can bind to SARS-CoV-2 and potentially induce the systemic viral spreading, entry, and infection of ACE2-expressing cells (Fig. 5).
Adipose tissue is widely distributed throughout the body not only in visceral (mesenteric/omental fat) and subcutaneous (subcutaneous fat) regions but also in parts of the lung (intrathoracic fat), pancreas (pancreatic fat), heart (epicardial fat), and kidney (perirenal fat). Because the virus can infect multiple organs beyond the respiratory tract, including the kidneys, heart, liver, brain, pancreas, and blood (42,43), SARS-CoV-2 also possibly invades, infects, and resides in the adipose tissue found in these organs.
GRP78 plays an important role in the viral protein production, folding, and/or assembly of many viruses, including dengue virus, Japanese encephalitis virus, human cytomegalovirus, Ebola virus, and hepatitis B virus (37,46–50). The inhibition of GRP78 can disrupt the entry and/or production of these viruses (19). A recent study has shown that AR12 (OSU-03012), a potent inhibitor of PDK1/AKT signaling, reduces GRP78 expression and inhibits SARS-CoV-2 replication (22). During the course of evolution, viruses have somehow acquired the ability to utilize GRP78 functions not only for entry into host cells but also for the production and assembly of viral proteins facilitating viral replication (Fig. 5).
Cell surface GRP78 has been shown to be associated with the activation of proinflammatory transcription factors (23). Cell surface GRP78 promotes NF-κB activation in endothelial cells and increases the expression levels of ICAM-1 and VCAM-1, accelerating the development of atherosclerotic lesions (52). JNK/STAT3 activation mediated by cell surface GRP78 increases the cell growth and migration of breast cancer (53). The binding of SARS-CoV-2 to GRP78 might induce the activation of proinflammatory transcription factors and possibly contribute to deleterious inflammatory responses, such as immune activation and cytokine amplification, in COVID-19 patients (Fig. 5).
A recent study showed that GRP78 is also involved in the egress of β-coronaviruses, including SARS-CoV-2, and is released together with viruses via the lysosomal exocytic pathway (21). These pathophysiological features of GRP78 might also contribute to the severe progression and outcome of COVID-19.
2- Zhang L, Cheng J, Shen J, Wang S, Guo C, Fan X. Ghrelin Inhibits Intestinal Epithelial Cell Apoptosis Through the Unfolded Protein Response Pathway in Ulcerative Colitis. Front Pharmacol. 2021;12:661853. Published 2021 Mar 10. doi:10.3389/fphar.2021.661853 ,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988211/ , When the cells were treated with ghrelin, the expression of GRP78 and CHOP, the phosphorylation of ERK, JNK, and eIF2, and the levels of proapoptosis proteins caspase-3 and BAX were all decreased and the expression of Bcl-2 was increased
3- Jafari, A., Sadeghpour, S., Ghasemnejad-Berenji, H. et al. Potential Antioxidative, Anti‐inflammatory and Immunomodulatory Effects of Ghrelin, an Endogenous Peptide from the Stomach in SARS-CoV2 Infection. Int J Pept Res Ther 27, 1875–1883 (2021). , https://link.springer.com/article/10.1007/s10989-021-10217-9 , 4- Almeida MH, Dantas JR, Barone B, et al. Residual C-peptide in patients with Type 1 diabetes and multiethnic backgrounds. Clinics (Sao Paulo). 2013;68(1):123-126. doi:10.6061/clinics/2013(01)rc02 , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552451/