Language：English   Publisher：Journal of Clinical Endocrinology and Metabolism  

Context Diabetic retinopathy (DR) is a common microvascular complication of diabetes, and identifying the risk factors for severe DR is important. Objective We aimed to investigate the relationship between severe DR and the extracellular water to total body water ratio (ET ratio). Methods Retrospective cross-sectional study at the Department of Endocrinology, Metabolism, and Diabetes, Kyushu University Hospital. A total of 205 adults with type 2 diabetes (T2D) were included. The patients were divided into 2 groups: nonproliferative DR (non-PDR; n = 161, 126 with no DR and 35 with simple DR) and proliferative DR (PDR; n = 44, 18 with preproliferative DR and 26 with PDR). The ET ratio was measured using bioelectrical impedance analysis. Results The ET ratio was significantly higher in the PDR group than in the non-PDR group (0.390 vs 0.398; P <. 0001). Multivariate logistic regression analysis showed that the ET ratio was significantly associated with PDR, independent of known risk factors for DR progression. In the subgroup analysis by age, multivariate logistic regression analysis revealed a significant association between the ET ratio and PDR, independent of known risk factors for DR progression in patients younger than 60 years. However, in patients 60 years and older, only the urinary albumin to creatinine ratio (UACR) showed a significant association with PDR in a model using the UACR and the ET ratio. Conclusion In patients with T2D younger than 60 years, the ET ratio may be a useful indicator for identifying severe DR.

DOI： 10.1210/clinem/dgae768

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PubMed

Language：English   Publisher：Plos One  

The Cre-loxP strategy for tissue-specific gene inactivation has become a widely employed tool in several research studies. Conversely, inadequate breeding and genotyping without considering the potential for non-specific Cre-recombinase expression may lead to misinterpretations of results. Nestin-Cre transgenic mice, widely used for the selective deletion of genes in neurons, have been observed to have an incidence of Cre-line germline recombination. In this study, we attempted to generate neuron-specific Glucagon-like peptide 1 receptor (Glp1r) knock-out mice by crossing mice harboring the Nestin-Cre transgene with mice harboring the Glp1r gene modified with loxP insertion, in order to elucidate the role of Glp1r signaling in the nervous system. Surprisingly, during this breeding process, we discovered that the null allele emerged in the offspring irrespective of the presence or absence of the Nestin-Cre transgene, with a high probability of occurrence (93.6%). To elucidate the cause of this null allele, we conducted breeding experiments between mice carrying the heterozygous Glp1r null allele but lacking the Nestin-Cre transgene. We confirmed that the null allele was inherited by the offspring independently of the Nestin-Cre transgene. Furthermore, we assessed the gene expression, protein expression, and phenotype of mice carrying the homozygous Glp1r null allele generated from the aforementioned breeding, thereby confirming that the null allele indeed caused a global knock-out of Glp1r. These findings suggest that the null allele in the NestinCre-Glp1r floxed breeding arose due to germline recombination. Moreover, we demonstrated the possibility that germline recombination may occur not only during the spermatogenesis at testis but also during epididymal sperm maturation. The striking frequency of germline recombination in the Nestin-Cre driver underscores the necessity for caution when implementing precise breeding strategies and employing suitable genotyping methods.

DOI： 10.1371/journal.pone.0296006

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PubMed

Language：Japanese  

Language：Japanese