Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, HR‑10000 Zagreb, Croatia.
Molecular Biology Department, Rudjer Boskovic Institute, HR‑10000 Zagreb, Croatia.
Int J Mol Med. 2021 Apr;47(4). doi: 10.3892/ijmm.2021.4893. Epub 2021 Mar 2.
The relationship between hemochromatosis and diabetes has been well established, as excessive iron deposition has been reported to result in impaired function of the endocrine and exocrine pancreas. Therefore, the objective of the present study was to analyze the effects of iron accumulation on the pancreata and glucose homeostasis in a bone morphogenetic protein 6‑knockout () mouse model of hemochromatosis. The sera and pancreatic tissues of wild‑type (WT) and mice (age, 3 and 10 months) were subjected to biochemical and histological analyses. In addition, F‑fluorodeoxyglucose biodistribution was evaluated in the liver, muscle, heart, kidney and adipose tissue of both animal groups. The results demonstrated that 3‑month‑old mice exhibited iron accumulation preferentially in the exocrine pancreas, with no signs of pancreatic injury or fibrosis. No changes were observed in the glucose metabolism, as pancreatic islet diameter, insulin and glucagon secretion, blood glucose levels and glucose uptake in the liver, muscle and adipose tissue remained comparable with those in the WT mice. Aging mice presented with progressive iron deposits in the exocrine pancreas, leading to pancreatic degeneration and injury that was characterized by acinar atrophy, fibrosis and the infiltration of inflammatory cells. However, the aging mice exhibited unaltered blood glucose levels and islet structure, normal insulin secretion and moderately increased α‑cell mass compared with those in the age‑matched WT mice. Additionally, iron overload and pancreatic damage were not observed in the aging WT mice. These results supported a pathogenic role of iron overload in aging mice leading to iron‑induced exocrine pancreatic deficiency, whereas the endocrine pancreas retained normal function.
血色病与糖尿病之间的关系已得到充分证实，因为已有报道称过量的铁沉积会导致内分泌和外分泌胰腺功能受损。因此，本研究旨在分析铁积累对血色病 BMP6 敲除（）小鼠模型中胰腺和葡萄糖稳态的影响。对野生型（WT）和 小鼠（年龄 3 个月和 10 个月）的血清和胰腺组织进行生化和组织学分析。此外，还评估了 F-氟脱氧葡萄糖在两组动物的肝脏、肌肉、心脏、肾脏和脂肪组织中的分布。结果表明，3 个月大的 小鼠表现出铁在胰腺外分泌部的优先积累，没有胰腺损伤或纤维化的迹象。葡萄糖代谢没有变化，胰腺胰岛直径、胰岛素和胰高血糖素分泌、肝、肌肉和脂肪组织中的血糖水平和葡萄糖摄取与 WT 小鼠相当。衰老的 小鼠表现出胰腺外分泌部进行性铁沉积，导致胰腺退化和损伤，表现为腺泡萎缩、纤维化和炎症细胞浸润。然而，与年龄匹配的 WT 小鼠相比，衰老的 小鼠血糖水平和胰岛结构不变，胰岛素分泌正常，α细胞质量适度增加。此外，衰老的 WT 小鼠中未观察到铁过载和胰腺损伤。这些结果支持铁过载在衰老的 小鼠中起致病作用，导致铁诱导的外分泌胰腺功能不全，而内分泌胰腺保持正常功能。
