283-OR: Adipose Stromal Cells Increase Insulin Sensitivity and Decrease Liver Gluconeogenesis in a Type 1 DM Mouse Model

Diabetic ketoacidosis (DKA) is a serious complication of hyperglycemic emergency due to insulin deficiency through accelerated liver gluconeogenesis and glycogenolysis. DKA is most common in T1D. Islet cells or parncreas transplantation are alternatives to insulin injection in treating T1D but only suitble for a small number of patients. This study aimed to explore the effects and mechanism of adipose stromal cells on liver gluconeogenesis and insulin sensitivity in an insulin-depended type 1 diabetic mouse model. We obtained stromal vascular fractions from wild-type inguinal adipose tissue and transplanted into the peritoneal cavity of type I diabetic Akita (Ins2^Akita) mice. We found that injection of 5x10⁶ SVF cells from wild type adipose tissue significantly decreased the pro-inflammatory genes of TNF-α, IL-1β, IL-33, iNOS and DPP4 expression in liver and increase anti-inflammatory factor of IL-10 and Foxp3 expression in blood serum and liver tissue seven days after injection. Moreover, mRNA expression of g6pc and pck1 was significantly decreased in liver of Akita mice. Furthermore, administration of 5x10⁶ or 1x10⁷ SVF cells from wild type adipose tissue significantly increased insulin sensitivity, reduced fasting blood glucose, and restored glucose-responsive c-peptide expression when compared to the untreated Akita group. Together, these findings suggest that adipose-derived SVF cells suppress liver inflammation, regulate liver gluconeogenesis, and improve insulin sensitivity in a type 1 diabetes mellitus animal model. Therefore, adipose SVF cells might be a novel cellular therapeutic strategy to maintain liver gluconeogenesis steady in T1D.