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Effect of caloric restriction in the regulation Sirt 1, Sirt 4 and AMPK on the secretory function of beta pancreatic cells in vivo and in vitro

Abstract

In recent decades, the scientific community has shown great interest in studies on the signaling pathways involving protein regulators of the disease's development such as obesity and diabetes. For 2025, it is estimated that the prevalence of diabetes mellitus is around 9% of the adult population. Obesity and diabetes mellitus are multifactor syndromes and recent studies indicate that the development of them is closely related to imbalance on food intake. Beyond the imbalance on food intake, modulate environmental and genetic factors induce the onset of these diseases. In this context, the emphasis given to the control of food intake, specifically for caloric restriction, emerges as the modulator of metabolic pathways preventing such diseases. Caloric restriction active cellular mechanisms responsible delayed of the onset of such syndromes, promoting survival of these individuals. These benefits, especially in subject longevity are assigned to regulatory proteins that on the one hand reduce the secretion of insulin and, secondly increase peripheral sensitivity to this hormone. Among the proteins that are activated or not, depending on caloric restriction and coordinate the secretion and signaling pathway of insulin, the protein deserves emphasis of the family Sirtuins and AMPK. Sirt 1 and Sirt 4 are highly expressed in the pancreatic islets and have a fine control on the secretion of insulin. The Sirt 1 behaves as the control positive and Sirt 4 as repressor of the insulin secretion. In addition, the AMPK is part of the signaling pathway of metformin and participates in many metabolic pathways. The AMPK inhibits gluconeogenesis, the fatty acids and cholesterol synthesis. So when AMPK is active it control weight and increased peripheral sensitivity to insulin. Thus, the goal of this study is to evaluate the effect of caloric restriction of 60% with respect to control over gene expression and protein of Sirt 1 and Sirt 4 in secretion of insulin both in vivo and from isolated pancreatic islets. Also, determine the expression of AMPK, depending on caloric restriction on insulin secretion from both in vivo and in vitro. This project can provide new strategies to prevent diseases such as diabetes and obesity promoting longevity. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
AMARAL, MARIA ESMERIA C.; RIBEIRO, ROSANE A.; VANZELA, EMERIELLE C.; BARBOSA-SAMPAIO, HELENA C. Reduced AMPK2 protein expression restores glucose-induced insulin secretion in islets from calorie-restricted rats. International Journal of Experimental Pathology, v. 97, n. 1, p. 50-55, FEB 2016. Web of Science Citations: 3.

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