%0 Journal Article
%T Islet -Cell Mass Preservation and Regeneration in Diabetes Mellitus: Four Factors with Potential Therapeutic Interest
%A Jose Manuel Mellado-Gil
%A Nadia Cobo-Vuilleumier
%A Benoit R. Gauthier
%J Journal of Transplantation
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/230870
%X Islet ¦Â-cell replacement and regeneration are two promising approaches for the treatment of Type 1 Diabetes Mellitus. Indeed, the success of islet transplantation in normalizing blood glucose in diabetic patients has provided the proof of principle that cell replacement can be employed as a safe and efficacious treatment. Nonetheless, shortage of organ donors has hampered expansion of this approach. Alternative sources of insulin-producing cells are mandatory to fill this gap. Although great advances have been achieved in generating surrogate ¦Â-cells from stem cells, current protocols have yet to produce functionally mature insulin-secreting cells. Recently, the concept of islet regeneration in which new ¦Â-cells are formed from either residual ¦Â-cell proliferation or transdifferentiation of other endocrine islet cells has gained much interest as an attractive therapeutic alternative to restore ¦Â-cell mass. Complementary approaches to cell replacement and regeneration could aim at enhancing ¦Â-cell survival and function. Herein, we discuss the value of Hepatocyte Growth Factor (HGF), Glucose-Dependent Insulinotropic Peptide (GIP), Paired box gene 4 (Pax4) and Liver Receptor Homolog-1 (LRH-1) as key players for ¦Â-cell replacement and regeneration therapies. These factors convey ¦Â-cell protection and enhanced function as well as facilitating proliferation and transdifferentiation of other pancreatic cell types to ¦Â-cells, under stressful conditions. 1. Diabetes Mellitus and ¦Â-Cell Regeneration The global incidence of Diabetes Mellitus (DM) has increased alarmingly in the past ten years, becoming one of the most common chronic diseases. It is estimated that this disorder will affect 552 million people by 2030 (http://www.idf.org/media-events/press-releases/2011/diabetes-atlas-5th-edition). Changing lifestyle leading to reduced physical activity and increased obesity has been pointed as the major culprit for this increase. DM is a group of metabolic diseases characterized by hyperglycemia due to defects in insulin secretion by pancreatic ¦Â-cells, insulin action on target tissues, or both [1]. Based on its etiology, DM has been classified into four main groups [1]; (1) Type 1 DM (T1DM) that results from lack of insulin production due to selective autoimmune destruction of pancreatic ¦Â-cells; (2) Type 2 DM (T2DM) caused by a combination of insulin resistance in the main target tissues (liver, muscle, and fat) and inadequate compensatory insulin secretion response by ¦Â-cells; (3) other specific type of diabetes which includes the genetic defects of the ¦Â-cell;
%U http://www.hindawi.com/journals/jtrans/2012/230870/