Abstract
In recent years, the concept of preserving and/or replenishing the functional β-cell mass vital to sustain insulin output and normalized blood glucose levels has gained much interest as a therapeutic approach in regenerative medicine for the treatment of Diabetes Mellitus. Herein, we surveyed the diabetes area patent literature published in recent years to identify novel uprising therapeutic targets specifically implicated in regeneration and survival. One hundred and sixty nine international patent applications filed under the Patent Cooperation Treaty (PCT) (hereinafter, patents or applications) were highlighted from which 8 particular targets stood out with more than 4 patents published within the last few years. Not surprisingly, GLP-1 analogues and DPP-4 inhibitors along with GPR119 agonists and SGLT2 inhibitors were among the top ranked candidates. However, new emerging targets into the field of regenerative medicine for the treatment of diabetes include: 1) BACE-2; a protease that was recently shown to cleave the plasma membrane glycoprotein TMEM27 (also called collectrin) resulting in the inhibition of pancreatic β cell proliferation and insulin secretion, 2) GIP; a 42 amino acid incretin hormone that potentiates glucose induce insulin secretion and protect β-cells against cytokinemediated apoptosis, 3) neurturin; a neurotrophic factor capable of improving blood glucose levels in high fat diet treated animals, and 4) LRH-1, an orphan nuclear receptor that improves islet viability. These novel targets along with GPR119 are further discussed in this review.
Keywords: Apoptosis, BACE-2, β-cells, diabetes, GIP, islet, LRH-1, neurturin, proliferation, GPR119.
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