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Anonymous ID: 3437f3 Aug. 1, 2020, 1:19 p.m. No.10151746   🗄️.is 🔗kun   >>2386

>>10151732

Possible Molecular Mechanisms of Hydroxychloroquine in Diabetes Mellitus

 

HCQ has multiple therapeutic properties, many of them not being fully understood at a molecular level. But its therapeutic effect has been found to possess anti-inflammatory, immunomodulating, anti-infective, and antithrombotic actions [43].

 

HCQ inhibits the degradation of insulin enhancing the metabolic effects of the hormone to improve insulin sensitivity [44]. The metabolic effect of HCQ is reducing dissociation of insulin from its receptor (tyrosine kinase) and increase the biologic half-life of insulin receptor complex which prolongs the action of insulin [16].

 

The possible explanation for the glucose-lowering effect of HCQ maybe that HCQ stabilizes intracellular lysosomes and slows the breakdown of the internalized insulin receptor complex [21] HCQ is an acidotrophic agent when intracellular concentration of HCQ reaches high, intracellular pH is raised causing inactivation of proteolytic enzyme (insulinase) that is responsible for degradation of insulin-resulting recirculation of substantial proportion of insulin in the active form [14].

 

It has been shown that during inflammation, cytokines such as tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) increased adiposity and insulin resistance by triggering key steps in the insulin signaling, hence influencing insulin and glucose metabolism [45]. TNFα decreases tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1) kinase and induces serine phosphorylation of IRS-1, which becomes an insulin receptor inhibitor in adipocytes and skeletal muscle cells. Thus, instead of acting only as a substrate for the insulin receptor, IRS-1 induces a negative feedback loop that declines the enzymatic activity of the receptor, thereby inhibiting its signaling pathway [46].

 

A retrospective cohort study done on patients’ diagnosis with either of RA or psoriasis treated with TNFα inhibitors, methotrexate, HCQ, and other nonbiologic DMARDs reported the reduced relative risk of DM for TNFα inhibitor and HCQ compared with other nonbiologic DMARDs [44]. Another retrospective cohort study conducted by Ozen and his coworkers on a total of 13,669 RA patients with and without incident DM were grouped into (i) methotrexate monotherapy, (ii) abatacept with or without synthetic DMARDs, (iii) any other DMARDs with methotrexate, and (iv) all other DMARDs without methotrexate, along with separate statin, glucocorticoid, and HCQ. RA patients who were on HCQ treatment showed a significant risk reduction of developing DM compared to groups who were not on HCQ treatment [47].

 

HCQ increases insulin sensitivity and reduces insulin resistance through its indirect effect by reducing inflammation [48]. HCQ has been reported to improve insulin sensitivity through the activation of protein kinase β (Akt) resulting in increased glucose uptake and glycogen synthesis [49].

 

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Anonymous ID: 3437f3 Aug. 1, 2020, 1:22 p.m. No.10151758   🗄️.is 🔗kun

In India since September 2013, for diabetic dyslipidaemia and hypertriglyceridaemia not controlled by statins in patients with type 2 diabetes.

Anonymous ID: 3437f3 Aug. 1, 2020, 1:26 p.m. No.10151784   🗄️.is 🔗kun   >>1958

In regards to HCQ and HIV this is what I have come across so far…..

 

Results: There was no significant difference in CD8 cell activation between the 2 groups (-4.8% and -4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, -0.6%; 95% CI, -4.8% to 3.6%; P = .80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (-85 cells/μL vs -23 cells/μL at week 48; difference, -62 cells/μL; 95% CI, -115 to -8; P = .03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P = .003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P = .03).

 

Conclusion: Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication.

 

https://pubmed.ncbi.nlm.nih.gov/22820788/

 

Then again everything is a lie