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Int. J. Mol. Sci. 2018, 19(6), 1713; https://doi.org/10.3390/ijms19061713

Responsiveness of Carnosine Homeostasis Genes in the Pancreas and Brain of Streptozotocin-Treated Mice Exposed to Dietary Carnosine

1
General Physiology Laboratory, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy
2
K.G. Jebsen Inflammation Research Centre, University of Oslo, 0318 Oslo, Norway
3
IRCCS—Istituto di Ricerche Farmacologiche Mario Negri, Department of Neuroscience, 20156 Milan, Italy
*
Authors to whom correspondence should be addressed.
Received: 19 May 2018 / Revised: 6 June 2018 / Accepted: 7 June 2018 / Published: 9 June 2018
(This article belongs to the Special Issue Amino Acids Transport and Metabolism)
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Abstract

In excitable tissues, the endogenous dipeptide carnosine (CAR, β-Ala-l-His) sustains homeostatic responses to various challenges. By eliciting hypoglycemic effects via actions on the autonomic nervous system and protection of pancreatic beta-cells, CAR is also relevant in diabetes. We investigated the expression of genes involved in CAR biosynthesis, degradation, and membrane transport pathways, in the pancreas and brains of mice treated with streptozotocin (STZ) and then exposed to dietary CAR. We induced hyperglycemia by STZ intraperitoneal injections; then, STZ-treated mice received drinking water with or without CAR for two weeks. We report that CAR administration elicits beneficial effects on blood glucose levels and weight loss in STZ-treated mice and, remarkably, on the insulin gene products in the pancreas, preserving gene expression from STZ challenge. Also, we describe mRNA downregulation of the Slc15a2/Pept2 (dipeptide transporter) and Cndp2 (intracellular dipeptidase) genes in the pancreas of hyperglycemic mice, and dysregulation of Carns1 (CAR synthase), Pept2 and Cndp2 in brains; interestingly, dietary CAR elicits counteracting effects. These expression patterns associate with variations of CAR content in tissues of mice. Overall, our report suggests a direct role of CAR in the diabetes-affected pancreas and in the diabetes-targeted CNS, proposing (dys)regulation of CAR’s homeostasis as a marker condition. View Full-Text
Keywords: dietary carnosine; di-tripeptides; Pept2/Slc15a2 oligopeptide transporter; Cndp2 dipeptidase; hyperglycemia; diabetes; pancreas; insulin; diabetes mouse models; homeostasis of small peptides dietary carnosine; di-tripeptides; Pept2/Slc15a2 oligopeptide transporter; Cndp2 dipeptidase; hyperglycemia; diabetes; pancreas; insulin; diabetes mouse models; homeostasis of small peptides
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Barca, A.; Gatti, F.; Spagnolo, D.; Ippati, S.; Vetrugno, C.; Verri, T. Responsiveness of Carnosine Homeostasis Genes in the Pancreas and Brain of Streptozotocin-Treated Mice Exposed to Dietary Carnosine. Int. J. Mol. Sci. 2018, 19, 1713.

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