[Incretin-based therapy in patients with type 1 diabetes mellitus]

GLP-1 has multiple physiological functions including glucose-dependent insulin secretion and glucagon suppression, delay of gastic emptying, suppression of hepatic glucose production, stimulation of beta cell replication and neogenesis, inhibition of beta cell apoptosis. All of these actions are beneficial for the treatment of diabetes. Therefore, incretin-based therapy may be still worthwhile as evidenced by studies demonstrating that beta cell mass may be preserved or expand in animals and that residual insulin secretion may be elevated to reduce the risk of hypoglycemia in patients treated with intensive insulin therapy, although the effect of GLP-1R agonists and DPP-4 inhibitors(DPP-4is) on beta cells may be small because destruction of beta cells leads to absolute insulin deficiency by cell-mediated autoimmune attack. Recent report also showed that DPP-4i might ameliorate an autoimmune attack against beta cells by restoring or increasing the number of regulatory T lymphocytes. Furthermore, GLP-1R-mediated signals might suppress the expression of chemokine ligand CXCL10 which binds to newly identified receptor TLR4 (Toll-like receptor 4), and impairs beta cell function and viability in diabetes. Taken together, incretin-based therapy may be worth testing in patients with type 1 diabetes.