Department of General and Visceral Surgery, Medical Center, Faculty of Medicine, University of Freiburg, University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.
Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.
Obes Surg. 2022 Jun;32(6):1980-1989. doi: 10.1007/s11695-022-06040-w. Epub 2022 Apr 6.
Response to metabolic surgery is heterogeneous and the metabolic states that underpin weight loss and metabolic improvement are still unclear. In this study, we investigate parameters of post-bariatric fasting glucoregulation and leverage artificial intelligence-assisted whole-slide image analyses to characterize associated immunohistologic features of the pancreas.
We performed either loop duodeno-jejunostomy (DJOS) with exclusion of 1/3 of total intestinal length, loop duodeno-ileostomy with exclusion of 2/3 of total intestinal length (DiOS), or a sham operation on 8-week-old male obese ZDF rats. Six months post-operative, we measured blood metabolites and hormones. Subsequently, pancreatic and intestinal tissue was removed, formalin fixed, and paraffin embedded. Immunohistologic (IHC) analyses included proliferating cell nuclear antigen (PCNA) to visualize the proliferation fraction and pancreatic and duodenal homeobox 1 (PDX 1) as a measure of pancreatic cell differentiation. For IHC quantification, all slides were digitalized and analyzed using QuPath. All analyzed slides were reviewed by two independent pathologists for correctness.
DJOS and DiOS were associated with preserved fasting insulin production compared to sham. Histopathologic evaluation showed significantly higher numbers of beta cells and specifically of clustered cell organization in DJOS and DiOS compared to sham. Cell proliferation (PCNA) was significantly elevated in DJOS and DiOS compared to sham.
In this interventional model of bariatric surgery in severe genetic diabetes, we demonstrate post-operative histologic and immunohistologic features of the pancreas associated with improved fasting glucose homeostasis.
代谢手术的反应具有异质性，而支持体重减轻和代谢改善的代谢状态仍不清楚。在这项研究中，我们研究了减重后空腹糖调节的参数，并利用人工智能辅助全切片图像分析来描述胰腺的相关免疫组织学特征。
我们对 8 周龄雄性肥胖 ZDF 大鼠进行了 loop 十二指肠空肠转流术（DJOS），排除了总肠长度的 1/3；loop 十二指肠回肠转流术（DiOS），排除了总肠长度的 2/3；或假手术。术后 6 个月，我们测量了血液代谢物和激素。随后，切除胰腺和肠道组织，福尔马林固定，石蜡包埋。免疫组织化学（IHC）分析包括增殖细胞核抗原（PCNA）以观察增殖分数，以及胰腺十二指肠同源盒 1（PDX 1）作为胰腺细胞分化的测量。对于 IHC 定量分析，所有切片均进行数字化，并使用 QuPath 进行分析。所有分析的切片均由两名独立的病理学家进行正确性审查。
DJOS 和 DiOS 与 sham 相比，空腹胰岛素产生得到了保留。组织病理学评估显示，与 sham 相比，DJOS 和 DiOS 中的 beta 细胞数量明显增加，特别是细胞簇组织化程度更高。DJOS 和 DiOS 中的细胞增殖（PCNA）明显高于 sham。
在严重遗传糖尿病的这种减肥手术干预模型中，我们证明了术后胰腺的组织学和免疫组织学特征与改善空腹血糖稳态有关。
