Monomeric cocoa procyanidins enhances β‐cell function by increasing mitochondrial respiration

Abstract

A hallmark of type 2 diabetes (T2D) is β‐cell dysfunction and the eventual loss of functional β‐cell mass. Therefore, mechanisms that can improve β‐cell function could be used as a treatment for the millions of individuals with T2D. Recent studies have shown that monomeric, oligomeric and polymeric cocoa derived procyanidins have vastly different effects on obesity, insulin resistance and glucose tolerance during high fat feeding. Based on these previously published data, we hypothesized that cocoa derived procyanidins may have beneficial effects on improving β‐cell function. 832/13 INS‐1 derived β‐cells and primary rat islets cultured with monomeric cocoa procyanidins demonstrated enhanced glucose stimulated insulin secretion (GSIS), while cells cultured with total cocoa extract, oligomeric procyanidins or polymeric procyanidins demonstrated no improvement. The increased GSIS observed with culture in the presence of monomeric procyanidin fractions corresponded with enhanced mitochondrial respiration, suggesting improvements in β‐cell fuel utilization. We demonstrated upregulation of electron transport chain components Complex III, IV and V after culture with monomeric procyanidins. Monomeric procyanidins also resulted in an increased cellular redox state and increased glutathione concentration, which corresponds with Nrf2 nuclear localization. We propose a model by which cocoa derived monomeric procyanidins enhance the cellular redox state, allowing Nrf2 to migrate to the nucleus and enhance expression of key mitochondrial genes that results in enhanced GSIS and improved β‐cell function. These results suggest that cocoa derived monomeric procyanidins could be leveraged as a treatment modality for patients with T2D.Support or Funding InformationBYU MEG Grant to JST, Diabetes Action Research and Education Grant to JST, BYU ORCA Grant to JDR and BFB