Sawash M Mohammed, Robert N Bone, Jacqueline Del Carmen Aquino, Raghavendra G Mirmira, Carmella Evans-Molina, Heba M Ismail
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引用次数: 0
Abstract
Background: Knockout (KO) ferrets with the cystic fibrosis transmembrane conductance regulator (CFTR) exhibit distinct phases of dysglycemia and pancreatic remodeling prior to cystic fibrosis-related diabetes (CFRD) development. Following normoglycemia during the first month of life (Phase l), hyperglycemia occurs during the subsequent 2 months (Phase Il) with decreased islet mass, followed by a period of near normoglycemia (Phase Ill) in which the islets regenerate. We aimed to characterize islet hormone expression patterns across these Phases.
Methods: Immunofluorescence staining per islet area was performed to characterize islet hormone expression patterns in age matched CFTR KO and wild type (WT) ferrets, focusing on the first three phases.
Results: In Phase I, insulin staining intensity was higher in CF (p < 0.01) than WT but decreased in Phase III (p < 0.0001). Glucagon was lower in CF during Phases I and increased in Phase III, while proinsulin decreased (p < 0.0001) Phases II and III. CF sections showed lower proinsulin-to-insulin ratio in Phase I (p < 0.01) and in Phase III (p < 0.05) compared to WT. Conversely, glucagon-to-insulin ratio was lower in CF in Phase I (p < 0.0001) but increased in Phase III (p < 0.0001). Mender's coefficient overlap showed higher overlap of insulin over proinsulin in CF sections in Phase II (p < 0.001) and Phase III (p < 0.0001) compared to WT. Mender's coefficient rate was higher in CF sections during Phase II (p < 0.001).
Conclusion: CF ferret islets revealed significant immunofluorescent staining changes compared to WT during various phases of disease, providing insights into CRFD pathophysiology.
背景：携带囊性纤维化跨膜传导调节剂（CFTR）的基因敲除（KO）雪貂在囊性纤维化相关糖尿病（CFRD）发展之前表现出不同的血糖异常和胰腺重塑阶段。在出生后的第一个月血糖正常（第一阶段），随后的2个月出现高血糖（第二阶段），胰岛质量减少，随后是一段接近正常血糖的时期（第二阶段），胰岛再生。我们的目的是表征胰岛激素在这些阶段的表达模式。方法：对年龄匹配的CFTR KO和野生型（WT）雪貂进行每个胰岛区域的免疫荧光染色，以前三个阶段为重点，表征其胰岛激素表达模式。结果：在I期中，CF的胰岛素染色强度更高（p p p p p p p p p p p p p p p p p p p）结论：CF雪貂胰岛在疾病的各个阶段与WT相比显示出显著的免疫荧光染色变化，为CRFD的病理生理提供了新的见解。
期刊介绍：
Islets is the first international, peer-reviewed research journal dedicated to islet biology. Islets publishes high-quality clinical and experimental research into the physiology and pathology of the islets of Langerhans. In addition to original research manuscripts, Islets is the leading source for cutting-edge Perspectives, Reviews and Commentaries.
Our goal is to foster communication and a rapid exchange of information through timely publication of important results using print as well as electronic formats.
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