Expression of sirtuins and its role on the control of insulin secretion in mouse pancreatic islets cultured in amino acid deficient medium

Abstract

Malnutrition is a public health problem and is associated with the development of chronic diseases in adulthood such as diabetes mellitus type 2 (DM2). In different organisms, the maintenance of homeostasis and survival depends on the ability to detect changes in nutrient levels in the external environment and adjust the intracellular processes of biosynthesis and degradation. Nutrient sensing is mediated by protein kinase activity in regulating metabolic activity through phosphorylation of several substrates. Another class of sensors can alter the cellular physiology by deacetylation of specific substrates. Sirtuins (Sirts) belong to the class of deacetylases that use nicotinamide adenine dinucleotide (NAD +) as cosubstrate in the deacetylation reaction. In pancreatic islets, Sirts 1 and 4 have been identified as regulators of insulin secretion. Activation of Sirt 1 reduces the degree of acetylation of transcription factor FoxO1 and expression of uncoupling protein (UCP) 2. Sirt 4 plays a role in insulin secretion by ribosylation and inhibition of the enzyme glutamate dehydrogenase (GDH). The expression of UCP 2 and GDH are altered in pancreatic islets of malnourished mice and rats, but the involvement of sirtuins in this context has not yet been determined. This project will employ a new approach based on in vitro depletion of amino acids and seek to determine the expression of sirtuins in isolated pancreatic islets and their involvement in the process of insulin secretion.