Cornus Officinalis Increases Proliferation, Inhibits Cytokine-Induced Apoptosis, and Promotes the Oxidative Capacity of the Human 1.1B4 Pancreatic Cell Line

Type 1 diabetes (T1D) affects 1.25 million Americans with about 40,000 individuals newly diagnosed each year. T1D is caused by an autoimmune-induced loss of pancreatic β cells and subsequent deterioration of insulin production. Although exogenous insulin is an efficient treatment, there is a strong need to develop therapies that can inhibit the loss of β cells and promote their function. For this purpose, we have been analyzing the antidiabetic capability of Cornus officinalis (CF), which has been utilized in traditional Chinese medicine for over 2,000 years primarily for treatment of T2D. We hypothesize that CF may inhibit β cell destruction and promote β cell function. Using the human 1.1B4 pancreatic β cell line, we have examined the proliferative effect of CF treatment on 1.1B4 cells in a time- and dose-dependent manner via cell viability assays. Within two hours, CF rapidly and significantly induced 1.1B4 proliferation by over 300% as compared to controls. Activation of Th1 cytokines plays a detrimental role in the pathogenesis of T1D. Therefore, we determined whether CF can inhibit cytokine induced β cell death and promote β cell proliferation following treatment with Th1 cytokines of IL-1β, TNF-α, and IFN-γ. CF induced a 200% increase in 1.1B4 proliferation following Th1 cytokine treatment compared to controls. In addition, a metabolic analysis of CF induced 1.1B4 cells was examined using the Agilent Seahorse XF analyzer. At a two-hour time point, there was a remarkable increase in maximal respiratory and glycolytic capacity following CF treatment. Therefore, CF is a strong inducer of metabolism. Ongoing experiments will provide greater detail into the mechanism and metabolic role in which CF is promoting proliferation and metabolism and inhibiting cytokine-induced β-cell death.