Inhibition of the sodium-glucose co-transporter type 2 (SGLT2) has received growing acceptance as a novel, safe and effective means to improve glycemic control in patients with type 2 diabetes. Inhibition of SGLT2 lowers the renal glucose threshold and reduces plasma glucose by promoting glucose excretion in urine. Both animal studies and clinical trials in man suggest that SGLT2 inhibition has the potential to improve pancreatic β-cell function by reducing glucose toxicity. However, there is limited data exploring how reducing glucotoxicity via SGLT2 inhibition affects rates of β-cell proliferation and death throughout life in the context of insulin resistance and type 2 diabetes. SGLT2^−/− mice were backcrossed to the db/db strain to produce littermate control db/db-SGLT2^+/+ and experimental db/db-SGLT2^−/− mice. Mice were euthanized at 5, 12 and 20 weeks of age to collect plasma for glucose, insulin, lipid and cytokine measures, and pancreata for histological analysis including determination of β-cell mass and rates of proliferation and death. SGLT2 deletion in db/db mice reduced plasma glucose as early as 5 weeks of age and continued throughout life without changes in plasma lipids or cytokines. Reduced plasma glucose levels occurred in parallel with an increase in the relative β-cell volume and reduced frequency of β-cell death, and no apparent change in rates of β-cell proliferation. These data add to a growing body of evidence demonstrating that improved glycemic control achieved through SGLT2 inhibition can preserve β-cell function and endogenous insulin secretion by reducing glucose toxicity and rates of β-cell death.

抑制钠2型葡萄糖共转运蛋白（SGLT2）作为改善2型糖尿病患者血糖控制的一种新颖，安全，有效的手段已得到越来越多的接受。SGLT2的抑制通过促进尿液中葡萄糖的排泄降低了肾葡萄糖阈值并降低了血浆葡萄糖。动物研究和人体临床试验均表明，抑制SGLT2具有通过降低葡萄糖毒性来改善胰腺β细胞功能的潜力。然而，在胰岛素抵抗和2型糖尿病的情况下，探索通过SGLT2抑制降低糖毒性如何影响整个生命中β细胞增殖和死亡的速率的数据有限。SGLT2 ^-/-小鼠回交至db / db品系以产生同窝对照db / db-SGLT2 ^{+ / +}和实验性db / db -SGLT2 ^-/-小鼠。在5、12和20周龄对小鼠实施安乐死以收集血浆中的葡萄糖，胰岛素，脂质和细胞因子，并采集胰腺进行组织学分析，包括确定β细胞的质量以及增殖和死亡的速率。db / db中的SGLT2删除小鼠早在5周龄就降低了血浆葡萄糖，并且在整个生命中持续存在，而血浆脂质或细胞因子却没有变化。血浆葡萄糖水平降低与相对β细胞体积增加和β细胞死亡频率降低同时发生，并且β细胞增殖速率没有明显变化。这些数据增加了越来越多的证据，表明通过SGLT2抑制获得的改善的血糖控制可通过降低葡萄糖毒性和降低β细胞死亡的速率来保持β细胞功能和内源性胰岛素分泌。