论文部分内容阅读
Insulin deficiency-absolute or relative-is the shared, cardinal feature of both type 1 and type 2 diabetes (T1 and T2DM).Restoration of islet function and secretion of not only insulin but other important peptides could cure and/or reverse both major forms of diabetes.Restoration of islet function is necessary but not sufficient to fully restore metabolic health in people with T1 or T2DM.Control of autoimmunity will also be required for overcoming T1DM and control of insulin resistance will also be required for fundamental disease modification of T2DM.Abundant animal model and human data support the prospects for islet regeneration therapy in people with diabetes.Low levels of islet regeneration have been demonstrated even in people with T1DM for over 50 years duration.Other evidence supports that islet progenitor cells are the source of this new islet regeneration, and furthermore, these progenitors can be induced to develop into islets.The major challenges for development of diabetes-reversing approaches, therefore, are to identify safe and effective pharmaceutical agents to induce islet regeneration and to prevent islet destruction.T1DM represents the higher unmet clinical need but the more technically difficult target.Islet NeoGenesis Associated Protein (INGAP) provides a prospect for islet regeneration therapy.INGAP is a member of the Reg family of proteins.INGAP has been shown to stimulate pancreatic endogenous progenitor cells to differentiate into insulin producing β-cells in multiple species.INGAP Peptide (ExsulinTM) is the patented synthetic 15 amino acid (108-114) portion of the patented full length INGAP native 175-amino acid protein.Published phase 2 trials of over 200 T1 and insulin dependent T2 diabetes showed evidence of neogenesis and improved glycemic control in response to 3 months therapy with INGAP Peptide.The evidence suggesting the promise of INGAP Peptide as a therapeutic agent will be summarized and the challenges of T1 DM therapeutic development discussed.