Islet β-Cell Mass Preservation and Regeneration in Diabetes Mellitus : Four Factors with Potential Therapeutic Interest

Abstract EN

Islet β-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 β-cells from stem cells, current protocols have yet to produce functionally mature insulin-secreting cells.

Recently, the concept of islet regeneration in which new β-cells are formed from either residual β-cell proliferation or transdifferentiation of other endocrine islet cells has gained much interest as an attractive therapeutic alternative to restore β-cell mass.

Complementary approaches to cell replacement and regeneration could aim at enhancing β-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 β-cell replacement and regeneration therapies.

These factors convey β-cell protection and enhanced function as well as facilitating proliferation and transdifferentiation of other pancreatic cell types to β-cells, under stressful conditions.