SAT044 Cornus officinalis Decreases Incidence Of Type 1 Diabetes Onset And Hyperglycemia In The Non-obese Diabetic Mouse

Abstract

Abstract Disclosure: J.D. Fletcher: None. G.E. Olsson: None. B.R. Burkhardt: None. Currently, there is only one FDA recently approved interventional agent (teplizumab) that can delay the onset of Type 1 Diabetes (T1D) by slowing the clinical progression of pancreatic β-cell autoimmunity and inhibiting the eventual loss of insulin production. Cornus officinalis (CO) is a highly popular ethnopharmacological treatment for diabetes and has been actively studied by our research group. Our earlier findings revealed in vitro that CO application to the pancreatic 1.1B4 β-cell line can promote pancreatic β-cell viability, metabolic activity, prevention of cytokine mediated cell death and expression of important cytoprotective pathways through promotion of autophagy and the KEAP1-Nrf2 mediated antioxidant response (PMID: 36100124 and 31255730). To further determine the clinical efficacy and biological effect of CO in-vivo, we investigated if oral delivery of CO was capable of inhibiting or delaying the onset of T1D in the non-obese diabetic (NOD) mouse (n = 7 to 10). Ten-week-old NOD male mice were given CO or water by oral gavage for 14 weeks once daily 5 days per week. Our experimental groups consisted of CO treated (CT), water treated (WT), and a no treatment or handling control group (NTH). CO was prepared by water extraction from a commercial source (Evergreen) at a concentration of 250 mg/ml and delivered by oral gavage in 200 µl. Glucose levels were measured every 3 days via glucometer (Contour Next) from tail vein collections. Diabetic onset was determined by two independent readings above 250 mg/dl. T1D incidence per group was as follows: CO (30%), WT (60%) and NTH (86%). Diabetic onset was significantly different between groups (Log rank test, p < 0.05). In addition, appearance of hyperglycemia (single glucose reading >130 mg/dl) was delayed in the CO treated NOD mice as compared to WT and NTH groups (p < 0.001). Further analysis is ongoing examining the concentration of c-peptide and determination of pancreatic insulitis by H&E staining. No harmful effects were observed in the CT group and body weights did not differ across experimental groups. In conclusion, our findings suggest that CO may have therapeutic potential as both a safe and effective interventional agent to delay the onset of T1D. Presentation: Saturday, June 17, 2023