Hyperinsulinemic hypoglycemia syndrome (HIHG) is a rare complication of roux-en-Y gastric bypass surgery. The pathology is associated with an excessive function of pancreatic beta-cells, and requires pancreas resection in patients that are recalcitrant to nutritional and pharmacological interventions. The exact prevalence is not clearly understood and the underlying mechanisms not yet fully characterized. We herein sought to perform histological and molecular examination of pancreatic sections obtained from a patient who developed HIHG as a complication of gastric bypass compared to 3 weight-matched controls. We studied markers of cellular replication and beta-cell differentiation by immunohistochemistry and immunofluorescence. HIHG after gastric bypass was characterized by a profound increase in beta-cell mass. Cellular proliferation was increased in islets and ducts compared to controls, suggesting unrestrained proliferation in HIHG. We also detected beta-cell differentiation markers in duct cells and occasional duct cells displaying both insulin and glucagon immunoreactivity. These histological observations suggest that beta-cell differentiation from ductal progenitor cells could also underly beta-cell mass expansion in HIHG. Altogether, our results can be construed to demonstrate that HIHG after gastric bypass is characterized by abnormal beta-cell mass expansion, resulting from both unrestrained beta-cell replication and neogenesis.

高胰岛素低血糖综合征（HIHG）是roux-en-Y胃搭桥手术的罕见并发症。病理与胰腺β细胞功能过度有关，需要对营养和药物干预不服的患者进行胰腺切除。尚不清楚确切的患病率，并且尚未充分表征潜在的机制。与3个体重匹配的对照相比，我们在本文中寻求对从患有HIHG并发胃旁路手术的患者获得的胰腺切片进行组织学和分子检查。我们通过免疫组织化学和免疫荧光研究了细胞复制和β细胞分化的标志物。胃绕道手术后的HIHG的特征在于β细胞质量的大幅增加。与对照相比，胰岛和导管中的细胞增殖增加，表明HIHG不受限制地增殖。我们还在导管细胞和偶有导管细胞中检测到显示胰岛素和胰高血糖素免疫反应性的β细胞分化标记。这些组织学观察表明，从导管祖细胞中分化出的β细胞也可能在HIHG中潜在地扩展了β细胞的质量。总而言之，我们的结果可以解释为表明，胃旁路手术后的HIHG的特征在于异常的β细胞质量膨胀，这是由于不受约束的β细胞复制和新生所致。我们还在导管细胞和偶有导管细胞中检测到显示胰岛素和胰高血糖素免疫反应性的β细胞分化标记。这些组织学观察表明，从导管祖细胞中分化出的β细胞也可能在HIHG中潜在地扩展了β细胞的质量。总而言之，我们的结果可以解释为表明，胃旁路手术后的HIHG的特征在于异常的β细胞质量膨胀，这是由于不受约束的β细胞复制和新生所致。我们还在导管细胞和偶有导管细胞中检测到显示胰岛素和胰高血糖素免疫反应性的β细胞分化标记。这些组织学观察表明，从导管祖细胞中分化出的β细胞也可能在HIHG中潜在地扩展了β细胞的质量。总而言之，我们的结果可以解释为表明，胃旁路手术后的HIHG的特征在于异常的β细胞质量膨胀，这是由于不受约束的β细胞复制和新生所致。