In pyruvate tolerance test, by treating the FOZ mice (Fat Aussie mice) with Pyruvate (Pyruvate/Body Weight: 2g/kg), there is unpublished evidence that mice may/will be dead within the next one or two days. It was also noted that blood glucose level of mice was dramatically reduced over time. I was just wondering, what is happening in Alms1 mutant mice when they are with pyruvate treatment? Any suggestions or speculations is highly appreciated. Thanks.
This may relate to very old findings about pyruvate potentiation of insulin secretion. There is a dose-dependent increase in insulin secretion when islets are exposed to exogenous pyruvate (which shifts the citrate/pyruvate balance between mitochondria and cytosol). This will cause hyperinsulinemia and consequently hypoglycemia.
Try searching the literature on PubMed, I'm sure you shouldn't have any problem finding the pertinent information.
On second thoughts, here you go:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1186223/pdf/biochemj00474-0219.pdf
Dear Dr . Alam, many thanks for your nice suggestions and information. The article has a good direction as well. Thanks. Sincerely, Eunus
Assuming the pyruvate penetrate cells and enter mitochondria's, the response might be a negative regulatory response to overloading of the mitochondria with Krebs cycle substrates. The negative feed-back in turn might activate severe hypophagia, which might lead to the reduction in blood glucose, which might be even associated with ketosis. Does this speculation makes sense, or supported by your data?
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