Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.
Levicure LTD, Tel Aviv, Israel.
Front Endocrinol (Lausanne). 2022 Oct 21;13:1028114. doi: 10.3389/fendo.2022.1028114. eCollection 2022.
Previous studies have reported that dual drug combinations consisting of γ-aminobutyric acid (GABA) together with a dipeptidyl-peptidase-4 inhibitor (DPP-4i), also a DPP-4i with a proton pump inhibitor (PPI), could improve pancreatic β-cell function and ameliorate diabetes in diabetic mice. In this study, we sought to determine if a triple drug combination of GABA, a DPP-4i and a PPI might have superior therapeutic effects compared with double drug therapies in the prevention and reversal of diabetes in the non-obese diabetic (NOD) mouse model of human type 1 diabetes (T1D). In a diabetes prevention arm of the study, the triple drug combination of GABA, a DPP-4i, and a PPI exhibited superior therapeutic effects in preventing the onset of diabetes compared with all the double drug combinations and placebo. Also, the triple drug combination significantly increased circulating C-peptide and serum insulin levels in the mice. In a diabetes reversal arm of the study, the triple drug combination was superior to all of the double drug combinations in reducing hyperglycemia in the mice. In addition, the triple drug combination was the most effective in increasing circulating levels of C-peptide and serum insulin, thereby significantly reducing exogenous insulin needs. The combination of GABA, a DPP-4i and a PPI appears to be a promising and easily scalable therapy for the treatment and prevention of T1D.
先前的研究报告表明，由 γ-氨基丁酸（GABA）与二肽基肽酶-4 抑制剂（DPP-4i）组成的双重药物组合，以及 DPP-4i 与质子泵抑制剂（PPI）组成的双重药物组合，可改善糖尿病小鼠的胰腺β细胞功能并改善糖尿病。在这项研究中，我们试图确定 GABA、DPP-4i 和 PPI 的三联药物组合是否比双药物疗法在预防和逆转非肥胖型糖尿病（NOD）小鼠的人类 1 型糖尿病（T1D）模型中的糖尿病方面具有更好的治疗效果。在研究的糖尿病预防部分，与所有双药物组合和安慰剂相比，GABA、DPP-4i 和 PPI 的三联药物组合在预防糖尿病发作方面表现出更好的治疗效果。此外，三联药物组合显著增加了小鼠循环 C 肽和血清胰岛素水平。在研究的糖尿病逆转部分，与所有双药物组合相比，三联药物组合在降低小鼠高血糖方面更为有效。此外，三联药物组合在增加循环 C 肽和血清胰岛素水平方面最为有效，从而显著减少对外源胰岛素的需求。GABA、DPP-4i 和 PPI 的组合似乎是治疗和预防 T1D 的一种有前途且易于扩展的疗法。
