Combination of clinical drugs for islet neogenesis and autoimmune suppression to develop a novel therapeutic strategy to reverse the disease progression of type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease caused by the response of T cells against pancreatic islets. The only treatment for T1D, nowadays, is insulin supplement, with still more than 50% patients suffered from diabetic complications, owing to the loss of dynamic control by islet β-cell. Therapeutic strategy for T1D should preserve islets function by regeneration of islet β-cell and autoimmune suppression to prevent newly-formed β-cell destruction. In this study, we develop a novel T1D therapeutic strategy by combining proton pump inhibitors (PPIs), which induce islet beta cell neogenesis, and anti-CD3 antibody, which deplete T cells to inhibit immune destruction of β-cell. The combination therapy reversed diabetes hyperglycemia in NOD mice. Islet recovery was proved through noninvasive image observation consequently. The infiltration of lymphocytes in pancreatic islet was reduced, and insulin-secretion function preserved. Moreover, combination therapy reduced CD8+ and CD4+ T cells, and elevated regulatory T cells (Treg) with TGF-β upregulated. Thus, we believe the success in the strategy of clinical drug combination therapy for islet neogenesis and immune suppression can speed up to use in clinical treatment to reverse disease progression in type 1 diabetes patients.