Non-invasive evaluation of GPR119 agonist effects on β-cell mass in diabetic male mice using 111In-exendin-4 SPECT/CT.
Non-invasive evaluation of GPR119 agonist effects on β-cell mass in diabetic male mice using 111In-exendin-4 SPECT/CT.
复制标题
使用 111In-exendin-4 SPECT/CT 无创评估 GPR119 激动剂对糖尿病雄性小鼠 β 细胞质量的影响。
作者：
T. Murakami;Hiroyuki Fujimoto;N. Fujita;K. Hamamatsu;Koji Matsumoto;N. Inagaki
胰腺β-细胞团（β-cell mass，β-cell mass）的纵向观察仍然具有挑战性，因为用于确定体内β-cell mass的非侵入性技术尚未建立。这些观察结果将有助于监测2型糖尿病（T2DM），这是一种涉及胰腺功能和功能丧失的进行性疾病。最近开发了一种靶向胰高血糖素样肽-1受体的111铟（In）标记exendin-4衍生物（[Lys12（111In-BnDTPA-Ahx）] exendin-4），作为一种有前途的非侵入性定量胰高血糖素的探针。在本研究中，我们使用111In-exendin-4单光子发射计算机断层扫描/计算机断层扫描（SPECT/CT）技术，在饮食限制的糖尿病前期db/db小鼠中研究DS-8500a（一种目前正在研究的新型G蛋白偶联受体119激动剂）治疗T2DM的疗效。在为期8周的研究中，与仅限饮食的小鼠相比，DS-8500a给药小鼠延迟并减弱了葡萄糖耐受不良的进展。db/db小鼠的111In-exendin-4 SPECT/CT显示在8周的干预期间胰腺中RI强度持续降低。在观察期结束时，与仅限饮食相比，DS-8500a减弱了这一降低，并保持了胰腺RI蓄积。该结果不仅通过使用[Lys12（111In-BnDTPA-Ahx）] exendin-4探针的离体胰腺分析得到证实，而且通过常规组织学分析得到证实。这些结果表明，DS-8500a在糖尿病前期db/db小鼠中可减缓体重减轻的进展，超过仅限饮食限制的进展。111In-exendin-4 SPECT/CT可用于活体内无创性纵向研究。
Longitudinal observation of pancreatic β-cell mass (BCM) remains challenging because non-invasive techniques for determining BCM in vivo have not been established. Such observations would be useful for the monitoring of type 2 diabetes mellitus (T2DM), a progressive disease involving loss of pancreatic BCM and function. An 111Indium (In)-labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4) targeting the glucagon-like peptide-1 receptor has been developed recently as a promising probe for quantifying BCM non-invasively. In this study, we used the 111In-exendin-4 single-photon emission computed tomography/computed tomography (SPECT/CT) technique to investigate the efficacy of DS-8500a, a novel G protein-coupled receptor 119 agonist currently under investigation for T2DM treatment, in prediabetic db/db mice under dietary restriction. During the 8-week study, treatment of mice with DS-8500a delayed and attenuated the progression of glucose intolerance compared to mice under dietary restriction alone. 111In-exendin-4 SPECT/CT of db/db mice revealed continuously decreasing RI intensity in the pancreas over the 8-week intervention. DS-8500a attenuated this decrease and preserved pancreatic RI accumulation compared with dietary restriction alone at the end of the observation period. This result was corroborated not only by ex vivo pancreatic analysis using the [Lys12(111In-BnDTPA-Ahx)]exendin-4 probe but also by conventional histological BCM analysis. These results indicate that DS-8500a attenuates the progression of BCM loss beyond that of dietary restriction alone in prediabetic db/db mice. 111In-exendin-4 SPECT/CT will be useful for non-invasive longitudinal investigation of BCM in vivo.
影响因子：
7.7
作者：
Xu, G;Stoffers, DA;Bonner-Weir, S
通讯作者：
Bonner-Weir, S