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bioRxiv · 10.1101/2020.11.20.391060

Could TDX-1 explain the changes observed in endocrine pancreas due to chronic cola drink consumption in rats? A global point of view

Cao, G.·Gonzalez, J.·Ortiz Fragola, J. P.·Muller, A.·Tumarkin, M.·Moriondo, M.·Azzato, F.·Blanco, M. V.·Milei, J.
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Abstract

In previous studies, we reported evidence showing that chronic cola consumption in rats impairs pancreatic metabolism of insulin and glucagon and produces some alterations typically observed in the metabolic syndrome (i.e, hyperglycemia, and hypertriglyceridemia) with an increase in oxidative stress. Of note, no apoptosis nor proliferation of islet cells could be demonstrated. In the present study, 36 male Wistar rats were divided in three groups to freely drink regular cola, light cola, or water (controls). We assessed the impact of the three different beverages in glucose tolerance, lipid levels, creatinine levels and immunohistochemical changes addressed for the expression of insulin, glucagon, PDX-1 and NGN3 in islet cells, to evaluate the possible participation of PDX-1 in the changes observed in and {beta} cells after 6 months of treatment. On the other hand, we assessed by stereological methods, the mean volume of islets (Vi) and three important variables, the fractional {beta}-cell area, the cross-sectional area of alpha (A -cell) and beta cells (A {beta}-cell), and the number of {beta} and cell per body weight. Cola drinking caused impaired glucose tolerance as well as fasting hyperglycemia and increase of insulin immunolabeling. Immunohistochemical expression for PDX-1 was significantly high in regular cola consumption group compared to control. In this case, we observed cytoplasmatic and nuclear localization. Likewise, a mild but significant decrease of Vi was detected after 6 months of cola drink consumption compared with control group. Also, we observed a significant decrease of fractional {beta} cell area compared with control rats. Accordingly, a reduced mean value of islet and {beta} cell number per body weight compared to control was detected. Interestingly, consumption of light cola increased the Vi compared to control. In line with this, a decreased cross-sectional area of {beta}-cells was observed after chronic consumption of both, regular and light cola, compared to controls. On the other hand, NGN3 was negative in all three groups. Our results support for the first time, the idea that TDX-1 plays a key role in the dynamics of the pancreatic islets after chronic consumption of sweetened beverages. The loss of islets cells might be attributed to autophagy, favored by the local metabolic conditions.

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Cao, G., Gonzalez, J., Ortiz Fragola, J. P., Muller, A., Tumarkin, M., Moriondo, M., Azzato, F., Blanco, M. V., Milei, J.. 2020-11-20. Could TDX-1 explain the changes observed in endocrine pancreas due to chronic cola drink consumption in rats? A global point of view. https://doi.org/10.1101/2020.11.20.391060

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