期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 49, 期 -, 页码 30-41出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2017.07.015
关键词
Cocoa; beta-Cell; Catechin; Insulin secretion; Mitochondrial respiration; Nrf2
资金
- Diabetes, Action, Research and Education Foundation
- American Diabetes Association
- Virginia Agricultural Experiment Station
- Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture
A hallmark of type 2 diabetes (T2D) is beta-cell dysfunction and the eventual loss of functional beta-cell mass. Therefore, mechanisms that improve or preserve beta-cell function could be used to improve the quality of life of individuals with T2D. Studies have shown that monomeric, oligomeric and polymeric cocoa flavanols have different effects on obesity, insulin resistance and glucose tolerance. We hypothesized that these cocoa flavanols may have beneficial effects on beta-cell function. INS-1 832/13-derived beta-cells and primary rat islets cultured with a monomeric catechin-rich cocoa flavanol fraction demonstrated enhanced glucose stimulated insulin secretion, while cells cultured with total cocoa extract and with oligomeric or polymeric procyanidin-rich fraction demonstrated no improvement. The increased glucose-stimulated insulin secretion in the presence of the monomeric catechin-rich fraction corresponded with enhanced mitochondrial respiration, suggesting improvements in beta-cell fuel utilization. Mitochondrial complex III, IV and V components are up-regulated after culture with the monomer-rich fraction, corresponding with increased cellular ATP production. The monomer-rich fraction improved cellular redox state and increased glutathione concentration, which corresponds with nuclear factor, erythroid 2 like 2 (Nrf2) nuclear localization and expression of Nrf2 target genes including nuclear respiratory factor 1 (Nrf1) and GA binding protein transcription factor alpha subunit (GABPA), essential genes for increasing mitochondria' function. We propose a model by which monomeric cocoa catechins improve the cellular redox state, resulting in Nrf2 nuclear migration and up-regulation of genes critical for mitochondrial respiration, glucose-stimulated insulin secretion and ultimately improved beta-cell function. These results suggest a mechanism by which monomeric cocoa catechins exert their effects as an effective complementary strategy to benefit T2D patients. (C) 2017 Elsevier Inc. All rights reserved.
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