Sustained kidney biochemical derangement in treated experimental diabetes : a clue to metabolic memory.

• Main Author: Oliveira, Antônio Anax Falcão de
• Publication Date: 2017
• Other Authors: Oliveira, Tiago Franco de, Bobadilla, Larissa Letícia, Garcia, Camila Carrião Machado, Berra, Carolina Maria, Pinto, Nadja Cristhina de Souza, Medeiros, Marisa Helena Gennari de, Mascio, Paolo Di, Zatz, Roberto, Loureiro, Ana Paula de Melo
• Format: Article
• Language: eng
• Source: Repositório Institucional da UFOP
• Download full: http://www.repositorio.ufop.br/handle/123456789/9183; https://doi.org/10.1038/srep40544

The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-β expression, reduced PGC-1α expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA. The sustained decrease of uric acid clearance in treated diabetes may support the prolonged kidney biochemical alterations observed after tight glycemic control, and this regulation is likely mediated by the sustained decrease of AMPK activity and the induction of inflammation. This manuscript proposes the first consideration of the possible role of hyperuricemia and the underlying biochemical changes as part of metabolic memory in diabetic nephropathy development after glycemic control.