1473-P: Combination Therapy with Dual-Function Peptide S1K and Insulin Reduces Blood Glucose Levels in Mouse Models of Type 1 Diabetes through Beta-Cell Regeneration and Immunosuppression

Abstract

β cell regeneration is necessary to cure patients with type 1 diabetes (T1D) whose β cells are destroyed by immune cells. Although insulin therapy can control blood glucose levels, it must be administered throughout life and occurs several side effects such as hypoglycemia. New β cell can be generated through neogenesis, β cell replication or transdifferentiation from other cells in diabetic animals. In addition to β cell regeneration, immunosuppression is another important mechanism to prevent β cell destruction, but currently any drugs haven’t been approved as immunosuppressants for T1D treatments yet. A novel 9-mer peptide, Shiloah 1000 (S1K) , has dual functions of β cell regeneration and immunosuppression. In streptozotocin-induced hyperglycemic mouse model, the number of mice recovered to normoglycemia was increased by the combined treatment of S1K and insulin compared to S1K or insulin alone. In addition, the combined treatment more increased the number of β cells than S1K or insulin alone. Interestingly, insulin/glucagon double-positive cells were increased by both combined and S1K alone treatments. The increase in the number of mice recovered to normoglycemia is considered to be due to β cell regeneration through α- to β-cell transdifferentiation by S1K. In the NOD mouse model, the combined treatment of S1K and insulin suppressed hyperglycemia more than insulin alone. In addition, the serum C-peptide levels were increased by both combined and S1K treatments, but not by insulin treatment. The increase in the serum C-peptide level suggest that β cells remain undestroyed by immunosuppression. Taken together, our data show that S1K, as a drug candidate for T1D treatment in combination with insulin reduces blood glucose levels in the T1D mouse models through β cell regeneration and immunosuppression, suggesting a potential role in preventing and curing T1D. Disclosure Y. Lee: Employee; Ensolbiosciences. H. Kim: Employee; Ensolbiosciences. J. Kim: Employee; Ensol Bioscience. Y. Jang: Employee; Ensolbiosciences.