Combined use of GABA and sitagliptin promotes human ?-cell proliferation and reduces apoptosis

?-Aminobutyric acid (GABA) and glucagon-like peptide-1 receptor agonist (GLP-1RA) improve rodent ?-cell survival function. In human ?-cells, GABA exerts stimulatory effects on proliferation anti-apoptotic effects, whereas GLP-1RA drugs have only limited proliferation. We previously demonstrated that sitagliptin (Sita), a dipeptidyl peptidase-4 inhibitor which increases endogenous GLP-1 levels, mediated synergistic protective effect in mice islets. However, it remains unclear whether this combination has similar ?-cell. To address question, we transplanted suboptimal mass of islets into immunodeficient NOD-scid-gamma with streptozotocin-induced diabetes, then treated them GABA, Sita, or both. The oral administration either Sita ameliorated blood glucose increased counts plasma insulin levels. Importantly, the combined generated significantly superior results all these responses, as compared to monotherapy one them. and/or regeneration, improved by combination, were Ki67 + , PDX-1 Nkx6.1 numbers. Protection against apoptosis was also drug combination. expression level ?-Klotho, protein ? cells, augmented. Our study indicates use produced greater therapeutic benefits, are likely due an enhancement decrease apoptosis.