Park S-Y, Bell G I
Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA.
Horm Metab Res. 2009 Jan;41(1):1-4. doi: 10.1055/s-0028-1087209. Epub 2008 Oct 23.
We have generated a transgenic mouse model (MIP- LUC) that allows real-time imaging of insulin-secreting pancreatic beta cells in living mice. The beta cells of MIP- LUC transgenic mice emit a light signal that can be visualized externally by bioluminescent imaging using specialized equipment. In order to determine whether the intensity of the bioluminescent signal accurately reflects changes in beta-cell mass rather than simply transcriptional modulation of the mouse insulin I promoter-luciferase transgene, we examined the correlation between the bioluminescent signal and the beta-cell mass in MIP- LUC mice fed a regular or high-fat Western diet. Male MIP- LUC mice were fed a standard rodent diet (5% of calories from fat) or a high-fat Western diet (42% from fat) beginning at 4 weeks of age. The bioluminescent signal and beta-cell mass were measured after 6 and 10 weeks on each diet. The body weight, beta-cell mass, and bioluminescent signal increased with age and increased further in mice fed a high-fat diet. There was a statistically significant correlation between beta-cell mass and bioluminescent signal (r (2)=0.660, p=0.00137). Thus, in vivo bioluminescent imaging can be used to noninvasively monitor changes in beta-cell mass in living MIP- LUC mice, and it complements other approaches for monitoring beta-cell mass in states of insulin resistance, obesity, and diabetes.
我们构建了一种转基因小鼠模型(MIP-LUC),可对活体内分泌胰岛素的胰腺β细胞进行实时成像。MIP-LUC转基因小鼠的β细胞发出的光信号,可通过使用专门设备的生物发光成像在体外进行可视化观察。为了确定生物发光信号的强度是否准确反映β细胞质量的变化,而非仅仅反映小鼠胰岛素I启动子-荧光素酶转基因的转录调控,我们检测了喂食常规或高脂西式饮食的MIP-LUC小鼠中生物发光信号与β细胞质量之间的相关性。雄性MIP-LUC小鼠从4周龄开始分别喂食标准啮齿动物饮食(脂肪提供5%的热量)或高脂西式饮食(脂肪提供42%的热量)。在每种饮食喂养6周和10周后,测量生物发光信号和β细胞质量。体重、β细胞质量和生物发光信号随年龄增加,在喂食高脂饮食的小鼠中进一步增加。β细胞质量与生物发光信号之间存在统计学显著相关性(r(2)=0.660,p=0.00137)。因此,体内生物发光成像可用于无创监测活的MIP-LUC小鼠β细胞质量的变化,并且它补充了在胰岛素抵抗、肥胖和糖尿病状态下监测β细胞质量的其他方法。