Stewie
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Really. Because where are those studies plastered all over the web lol.
Post valid concerns/studies that get met by pitry dish studies and over half the studies ignored with a You're wrong attitude with it. Well don't see anything proving my post are wrong.
Great follow up post. No value at all of course.
Wonder how much time both of you spend trying to refute people who post data that goes agasint your own agenda. Hey but look at this pitry dish study. And ignore 90 percent of the rest of your post and say you're wrong pal.
You do realize you posted a in-vitro murine model citation by Yaomin Chen et al. Proc Natl Acad Sci U S A. 2009."Metformin Facilitates Amyloid-β Generation by β- and γ-Secretases via Autophagy Activation."
Yet
From the full literature you cited:
Cell culture and drug treatment The human neuroblastoma cell lines SH-SY5Y andSY5Y
C99wereculturedaspreviouslydescribed [19].CellswerewashedtwiceinwarmDMEMbefore treatment with each drug at the indicated concentrations/for the indicated periods; only metformin was dissolved in DMEM supplemented with 10% fetal bovine serum (HyClone), 100 U/ml penicillin, and 100g/ml streptomycin. Doses and durations were: 2, 5, or 10mM metformin (Sigma-Aldrich, St. Louis, MO, USA) for 12 or 24h; 20M Compound C (6-[4-(2-Piperidin-1-ylethoxy)phenyl]-3-pyridin4-ylpyrazolo[1,5-a]pyrimidine) (Sigma-Aldrich, St. Louis, MO,USA)for1h(pre)treatment; 5mM3MA (3-methyladenine) (Sigma-Aldrich, St. Louis, MO, USA)for1h(pre)treatment. For cell starvation, cells were washed twice in warm DMEM and then incubated for 0.5, 1, 2, 4, or 6h.
MATERIALS AND METHODS Mice Transgenic mice (Tg6799) that overexpress both human APP 695 with the Swedish (K670N, M671L),Florida(I716V),andLondon(V717I)mutations; and mutated human (M146L and L286V), were generated. Heterozygous Tg6799 mice were intercrossed with B6/SJL mice (Taconic Farms Inc., NY, USA) to generate the desired genotypes. Mice were genotyped by PCR analysis of tail DNA; only females were used in the experiments. Age-matched female negative mice from similar crosses were used as wild-type controls. Animal care and procedures were performed in accordance with the Laboratory Animal Care Guidelines approved by Seoul National University. Drug injection/sample collection Metformin (final dose 200mg/kg)
I'll fill you in on couple of things here, Taeian.
First and foremost, in-vitro rarely if ever mimics in-vivo. in-vivo studies are useful for understanding static conditions, not so much for cellular movement(s) that occurs in breathing organisms. Yes, the citation you posted.
Secondly, we do not share the same hematological or immunological parameters as murine models. Yes, the citation you posted
Next, take a peek at the dosage(s) used 200mg/kg to induce cytotoxicity in these mice. The HED (human equivalent dose) to extrapolate murine->human the allometric scaling of 200mg/kg to that of a 90.718kg (200lb) individual, the dosage would be roughly 110,542.072mg of metformin. I'd say this would probably lead to a wee-bit more than amyloid generation.
For your pleasure and future use.
HED allometric scaling calculator:
If you're up for learning more, don't hesitate to ask.