Regulatory Connections between Iron and Glucose Metabolism

Fillebeen, Carine; Lam, Nhat Hung; Chow, Samantha; Botta, Amy; Sweeney, Gary; Pantopoulos, Kostas

doi:10.3390/ijms21207773

Cited by 33 publications

(34 citation statements)

References 129 publications

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“…Iron homeostasis is closely related to glucose metabolism [ 24 , 25 ]. Clinical studies suggested that deregulation of iron metabolism in iron overload disorders is associated with other metabolic dysfunction [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

A new mechanism of POCD caused by sevoflurane in mice: cognitive impairment induced by cross-dysfunction of iron and glucose metabolism

Zuo

Jinhong

et al. 2021

Aging

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Sevoflurane (Sev) is a commonly used anesthetic in hospitals that can cause neurotoxicity. Postoperative cognitive dysfunction (POCD) is a common clinical problem induced by some anesthetics. However, the exact mechanism of neurotoxicity induced by Sev is unclear. Here we studied a new mechanism of POCD induced by Sev. We treated 15-month-old mice with 2% Sev for 6 hours, and we had found that Sev causes POCD. Using isobaric tags for relative and absolute quantitation (iTRAQ), we found that the transporter and the metabolism of carbohydrates and inorganic ions were involved in the cognitive impairment induced by Sev. Using synchrotron radiation micro-X-ray fluorescence (μ-XRF), we showed that Sev caused the iron overload in the brain of 15-month-old mice. Subsequently, excessive iron led to oxidative stress and impaired mitochondrial function that further led to glucose metabolism disorder and reduced ATP production by regulating the expression of key enzyme genes or proteins including G6Pase, Pck1, and Cs. Meanwhile, Sev also inhibited the oxygen consumption rate and glucose absorption by downregulating the expression of glucose transporter 1 in cerebral vascular endothelial cells. The cross-dysfunction of iron and glucose metabolism caused the apoptosis in the cortex and hippocampus through Bcl2/Bax pathway. In conclusion, the data here showed a new mechanism that Sev caused apoptosis by cross-dysregulation of iron and glucose metabolism and induced energy stress in mice. Maintaining iron and glucose metabolism homeostasis may play an important role in cognitive impairment induced by Sev.

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Section: Discussionmentioning

confidence: 99%

A new mechanism of POCD caused by sevoflurane in mice: cognitive impairment induced by cross-dysfunction of iron and glucose metabolism

Zuo

Jinhong

et al. 2021

Aging

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“…In line with a causative role for iron in diabetic disease, dietary iron restriction has been reported to improve beta-cell function and glucose tolerance in ob/ob mice (84,144), and phlebotomy has been shown to improve insulin sensitivity, insulin secretion and glucose regulation in type 2 diabetes mellitus (T2DM) [152,153] even if clinical data, collected so far on iron depletion strategy, still appear inconclusive [154,155].…”

Section: Iron Dyshomeostasis Is Implicated In Diabetesmentioning

confidence: 99%

Iron Metabolism in Pancreatic Beta-Cell Function and Dysfunction

Marku

Galli

Marciani

et al. 2021

Cells

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Iron is an essential element involved in a variety of physiological functions. In the pancreatic beta-cells, being part of Fe-S cluster proteins, it is necessary for the correct insulin synthesis and processing. In the mitochondria, as a component of the respiratory chain, it allows the production of ATP and reactive oxygen species (ROS) that trigger beta-cell depolarization and potentiate the calcium-dependent insulin release. Iron cellular content must be finely tuned to ensure the normal supply but also to prevent overloading. Indeed, due to the high reactivity with oxygen and the formation of free radicals, iron excess may cause oxidative damage of cells that are extremely vulnerable to this condition because the normal elevated ROS production and the paucity in antioxidant enzyme activities. The aim of the present review is to provide insights into the mechanisms responsible for iron homeostasis in beta-cells, describing how alteration of these processes has been related to beta-cell damage and failure. Defects in iron-storing or -chaperoning proteins have been detected in diabetic conditions; therefore, the control of iron metabolism in these cells deserves further investigation as a promising target for the development of new disease treatments.

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“…A good example of a metabolically oriented MDS therapy is iron chelation, the primary effect of which was originally attributed to reduction in iron overload with consequent reduction in ROS and the pathological effects thereof on hematopoiesis. However, it has been shown that iron depletion exerts direct metabolic effects through improvement in insulin resistance in patients with hyperferritinemia [ 107 ]. According to retrospective analyses, iron chelation also delayed cardiac events in transfusion-dependent patients with MDS [ 108 ], whereas the randomized prospective TELESTO trial demonstrated that adverse events, including cardiac dysfunction, occurred approximately one year later in patients treated with iron chelation compared with placebo [ 91 ].…”

Section: Summary and Outlook: Clinical And Therapeutic Aspects Of Metabolic Changes In Mds Patientsmentioning

confidence: 99%

Myelodysplastic Syndromes and Metabolism

Balaian

Wobus

Bornhäuser

et al. 2021

IJMS

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Myelodysplastic syndromes (MDS) are acquired clonal stem cell disorders exhibiting ineffective hematopoiesis, dysplastic cell morphology in the bone marrow, and peripheral cytopenia at early stages; while advanced stages carry a high risk for transformation into acute myeloid leukemia (AML). Genetic alterations are integral to the pathogenesis of MDS. However, it remains unclear how these genetic changes in hematopoietic stem and progenitor cells (HSPCs) occur, and how they confer an expansion advantage to the clones carrying them. Recently, inflammatory processes and changes in cellular metabolism of HSPCs and the surrounding bone marrow microenvironment have been associated with an age-related dysfunction of HSPCs and the emergence of genetic aberrations related to clonal hematopoiesis of indeterminate potential (CHIP). The present review highlights the involvement of metabolic and inflammatory pathways in the regulation of HSPC and niche cell function in MDS in comparison to healthy state and discusses how such pathways may be amenable to therapeutic interventions.

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Regulatory Connections between Iron and Glucose Metabolism

Cited by 33 publications

References 129 publications

A new mechanism of POCD caused by sevoflurane in mice: cognitive impairment induced by cross-dysfunction of iron and glucose metabolism

A new mechanism of POCD caused by sevoflurane in mice: cognitive impairment induced by cross-dysfunction of iron and glucose metabolism

Iron Metabolism in Pancreatic Beta-Cell Function and Dysfunction

Myelodysplastic Syndromes and Metabolism

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