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Longitudinal observation of pancreatic β-cell mass (BCM) remains challenging because noninvasive techniques for determining BCM in vivo have not been established. Such observations would be useful for the monitoring of type 2 diabetes mellitus, a progressive disease involving loss of pancreatic BCM and function. An indium 111 (111In)–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 the BCM noninvasively. In the present study, we used the 111In-exendin-4 single-photon emission CT/CT (SPECT/CT) technique to investigate the efficacy of DS-8500a, a novel G protein–coupled receptor-119 agonist currently under investigation for type 2 diabetes mellitus treatment in prediabetic db/db mice under dietary restriction. During the 8-week study, the treatment of mice with DS-8500a delayed and attenuated the progression of glucose intolerance compared with mice under dietary restriction alone. 111In-exendin-4 SPECT/CT of db/db mice revealed continuously decreasing radioactive isotope (RI) intensity in the pancreas during 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. These results have shown that 111In-exendin-4 SPECT/CT will be useful for noninvasive longitudinal investigation of BCM in vivo.

Noninvasive Evaluation of GPR119 Agonist Effects on β-Cell Mass in Diabetic Male Mice Using 111In-Exendin-4 SPECT/CT