Gubra ApS, Agern Alle 1, 2970 Hørsholm, Denmark.
J Endocrinol. 2012 Sep;214(3):381-7. doi: 10.1530/JOE-11-0479. Epub 2012 Jul 3.
Recent data indicate that dipeptidyl peptidase 4 (DPP4) inhibitors have anti-inflammatory and β-cell-sparing effects in animal models of type 1 diabetes. To evaluate the effects of the DPP4 inhibitor linagliptin on β-cell mass and insulinitis, we examined the progression of diabetes (blood glucose >11 mmol/l) in non-obese diabetic (NOD) mice with terminal stereological assessment of cellular pancreatic changes. Female NOD mice were fed a normal chow diet or a diet containing linagliptin 0.083 g/kg chow for 60 days. At study end, the incidence of diabetes in linagliptin-treated mice was reduced by almost 50% compared with vehicle (10 of 31 mice vs 18 of 30 mice, P=0.021). The total islet mass and total β-cell mass, identified by insulin immunoreactivity, were greater in non-diabetic linagliptin-treated mice compared with non-diabetic vehicle-treated mice (P<0.01 for both) but were greatly reduced in diabetic mice irrespective of treatment. No changes were seen in the α, δ and γ endocrine cell pool. Moreover, the total mass of lymphocyte insulinitis was significantly reduced in linagliptin-treated mice compared with vehicle. The data indicate that linagliptin treatment delays the onset of diabetes in NOD mice by protecting β-cell mass.
最近的数据表明，二肽基肽酶 4（DPP4）抑制剂在 1 型糖尿病的动物模型中具有抗炎和β细胞保护作用。为了评估 DPP4 抑制剂利拉利汀对β细胞质量和胰岛炎的影响，我们通过对胰岛细胞的终末立体学评估，研究了非肥胖型糖尿病（NOD）小鼠糖尿病（血糖>11mmol/L）的进展。雌性 NOD 小鼠喂食标准食物或含有利拉利汀 0.083g/kg 食物的饮食 60 天。在研究结束时，与载体相比，利拉利汀治疗的小鼠糖尿病的发病率降低了近 50%（10/31 只小鼠 vs 18/30 只小鼠，P=0.021）。非糖尿病利拉利汀治疗的小鼠的总胰岛质量和总β细胞质量（通过胰岛素免疫反应鉴定）明显大于非糖尿病载体治疗的小鼠（两者均 P<0.01），但无论治疗与否，糖尿病小鼠的胰岛质量都大大降低。α、δ 和 γ 内分泌细胞库没有变化。此外，与载体相比，利拉利汀治疗的小鼠的淋巴细胞胰岛炎总质量明显降低。数据表明，利拉利汀治疗通过保护β细胞质量延迟了 NOD 小鼠糖尿病的发病。
