Iron overload in aging Bmp6 ‑/‑ mice induces exocrine pancreatic injury and fibrosis due to acinar cell loss

Znanstveni rad - Izvorni znanstveni rad

• Autor: Martina Pauk
• Autor: Vera Kufner
• Autor: Viktorija Rumenović
• Autor: Ivo Dumić‑Čule
• Autor: Vladimir Farkaš
• Autor: Milan Milošević
• Autor: Tatjana Bordukalo‑Nikšić
• Autor: Slobodan Vukičević
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (KATEDRA ZA ANATOMIJU)
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (KATEDRA ZA ZDRAVSTVENU EKOLOGIJU, MEDICINU RADA I SPORTA)
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti; Anatomija
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Javno zdravstvo i zdravstvena zaštita; Medicina rada i športa

Sažetak (engleski)

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 (Bmp6‑/‑) mouse model of hemochromatosis. The sera and pancreatic tissues of wild‑type (WT) and Bmp6‑/‑ mice (age, 3 and 10 months) were subjected to biochemical and histological analyses. In addition, 18F‑fluorodeoxyglucose biodistribution was evaluated in the liver, muscle, heart, kidney and adipose tissue of both animal groups. The results demonstrated that 3‑month‑old Bmp6‑/‑ 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 Bmp6‑/‑ 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 Bmp6‑/‑ mice leading to iron‑induced exocrine pancreatic deficiency, whereas the endocrine pancreas retained normal function.

• Ključne riječi (engleski): Acinar Cells / pathology; Bone Morphogenetic Protein 6 / genetics; Diabetes Mellitus / pathology; Hemochromatosis / pathology; Iron Overload / pathology
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: International Journal of Molecular Medicine
• Brojčani podaci: vol. 47, br. 4, 60
• p-ISSN: 1107-3756
• e-ISSN: 1791-244X
• DOI: https://doi.org/10.3892/ijmm.2021.4893
• URN:NBN: urn:nbn:hr:105:037867
• Datum objave publikacije: 2021-04
• URL dokumenta: http://www.spandidos-publications.com/10.3892/ijmm.2021.4893
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2021-06-25 09:24:22