Abstract
Islet transplantation is being considered as an alternative treatment for type 1 diabetes. Despite recent progress, transplant recipients continue to experience progressive loss of insulin independence. Cyanidin-3-O-Glucoside (C3G) has shown to be protective against damage that may lead to post-transplant islet loss. In this study, human islets cultured with or without C3G were treated with human amylin, Aβ1-42, H2O2, or rapamycin to mimic stresses encountered in the post-transplant environment. Samples of these islets were collected and assayed to determine C3G’s effect on cell viability and function, reactive oxygen species (ROS), oxidative stress, amyloid formation, and the presence of inflammatory as well as autophagic markers. C3G treatment of human islets exposed to either amylin or Aβ1-42 increased cell viability (p<0.01) and inhibited amyloid formation (p<0.01). A reduction in ROS and an increase in HO-1 gene expression as well as in vitro islet function were also observed in C3G-treated islets exposed to amylin or Aβ1-42, although not significantly. Additionally, treatment with C3G resulted in a significant reduction in the protein expression of inflammatory markers IL-1β and NLRP3 (p<0.01) as well as an increase in LC3 autophagic marker (p<0.05) in human islets treated with amylin, Aβ1-42, rapamycin, or H2O2. Thus, C3G appears to have a multi-faceted protective effect on human islets in vitro, possibly through its anti-oxidant property and alteration of inflammatory as well as autophagic pathways.
Highlights
Islet transplantation is being considered as a possible treatment for patients with type 1 diabetes
Understanding the mechanism of islet transplant failure remains a major focus of diabetes research in hopes of achieving lifelong insulin independence in transplant recipients
Studies have shown that oxidative stress, inflammatory damage, and amyloid plaque formation likely all play a role in the failure of islet allografts
Summary
Islet transplantation is being considered as a possible treatment for patients with type 1 diabetes. Existing evidences suggest that amylin aggregation induces processes that lead to the impairment of β-cell function and death contributing to the loss of islet β-cell mass [22,23,24]. One such process could be the disruption of mitochondrial membrane by the amyloid aggregates, thereby causing metabolic dysfunction with induction of oxidative stress and ROS production, and damage to islet cells [25, 26]. It is conceivable that C3G may be beneficial to human islets by protecting them against oxidative stress-induced damage, as well as preventing the formation and deposition of amyloid thereby enhancing their function
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