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

Pauk, Martina; Kufner, Vera; Dumić-Čule, Ivo; Farkaš, Vladimir; Milošević, Milan; Bordukalo Nikšić, Tatjana; Vukičević, Slobodan (2021) Iron overload in aging Bmp6−/− mice induces exocrine pancreatic injury and fibrosis due to acinar cell loss. International journal of molecular medicine, 47 (4). ISSN 1107-3756

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	bone morphogenetic protein 6 ; glucose homeostasis ; pancreas ; iron metabolism ; diabetes
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Znanstveni centar izvrsnosti za reproduktivnu i regenerativnu medicinu – istraživanja novih platormi i potencijala Volarević, Siniša; Vukičević, Slobodan; Ježek, Davor KK.01.1.1.01.0008 EK
Depositing User:	Vladimir Farkaš
Date Deposited:	19 May 2022 13:30
URI:	http://fulir.irb.hr/id/eprint/7380
DOI:	10.3892/ijmm.2021.4893

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