Excessive iron inhibits insulin secretion via perturbing transcriptional regulation of SYT7 by OGG1

Zhao, Xingqi; Ma, Ying; Shi, Munan; Huang, Miaoling; Xin, Jingyu; Ci, Shusheng; Chen, Meimei; Jiang, Tao; Hu, Zhigang; He, Lingfeng; Feiyan, Pan; Guo, Zhigang

doi:10.1007/s00018-023-04802-y

Cited by 6 publications

(3 citation statements)

References 48 publications

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“…Although we did not find any differences, the SNP is associated with glucose metabolism, particularly as it triggers decreased insulin sensitivity in subjects with normal glucose tolerance [43]. Recent studies confirm that high glucose intake decreased expression of hOGG1, while hOGG1-null mice had reduced insulin secretion [44][45][46][47]. Furthermore, the SNP increases the risk of bladder and gallbladder cancer [48,49].…”

Section: Discussionmentioning

confidence: 56%

Single-Nucleotide Polymorphisms in Base-Excision Repair-Related Genes Involved in the Risk of an Occurrence of Non-Alcoholic Fatty Liver Disease

Ziółkowska

Kosmalski

Kołodziej

et al. 2023

IJMS

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Oxidative stress is one of the pillars crucial in the development of a non-alcoholic fatty liver disease (NAFLD) and may cause DNA damage. Since the main pathway responsible for the repair of oxidative DNA damage is the base-excision repair (BER) pathway, we examined the relationship between the presence of different genetic variants of BER-associated genes and the risk of NAFLD. The study evaluates seven single nucleotide polymorphisms (SNPs) within five genes, hOGG1, APEX1, NEIL1, LIG3, LIG1, in 150 NAFLD patients and 340 healthy controls. The genotyping was performed using TaqMan probes and the results were presented as odds ratio with its corresponding 95% confidence interval. The following SNPs were assessed in the study: hOGG1 (rs1052133), APEX1 (rs176094 and rs1130409), NEIL1 (rs4462560), LIG3 (rs1052536), LIG3 (rs4796030), and LIG1 (rs20579). Four of the investigated SNPs, i.e., rs176094, rs1130409, rs4462560 and rs4796030, were found to be associated with NAFLD risk. Furthermore, the occurrence of insulin resistance in patients with steatosis depended on various LIG3 genetic variants. The findings imply the impact of genes involved in BER on NAFLD and fatty liver-related insulin sensitivity.

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Section: Discussionmentioning

confidence: 56%

Single-Nucleotide Polymorphisms in Base-Excision Repair-Related Genes Involved in the Risk of an Occurrence of Non-Alcoholic Fatty Liver Disease

Ziółkowska

Kosmalski

Kołodziej

et al. 2023

IJMS

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“…Research has revealed that iron overload inhibits insulin secretion and compromises islet β cell function through the downregulation of synaptotagmin 7 (SYT7), both in vivo and in vitro models [ 815 ]. This suggests SYT7might present a potential therapeutic target for T2DM.…”

Section: Ferroptosis In Pathologiesmentioning

confidence: 99%

The mechanism of ferroptosis and its related diseases

Feng,

Tang,

Wang

et al. 2023

Mol Biomed

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Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation of lipid peroxides, provides a novel avenue for delving into the intersection of cellular metabolism, oxidative stress, and disease pathology. We have witnessed a mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological and pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, and traumatic tissue injuries. By unraveling the intricate underpinnings of the molecular machinery, pivotal contributors, intricate signaling conduits, and regulatory networks governing ferroptosis, researchers aim to bridge the gap between the intricacies of this unique mode of cellular death and its multifaceted implications for health and disease. In light of the rapidly advancing landscape of ferroptosis research, we present a comprehensive review aiming at the extensive implications of ferroptosis in the origins and progress of human diseases. This review concludes with a careful analysis of potential treatment approaches carefully designed to either inhibit or promote ferroptosis. Additionally, we have succinctly summarized the potential therapeutic targets and compounds that hold promise in targeting ferroptosis within various diseases. This pivotal facet underscores the burgeoning possibilities for manipulating ferroptosis as a therapeutic strategy. In summary, this review enriched the insights of both investigators and practitioners, while fostering an elevated comprehension of ferroptosis and its latent translational utilities. By revealing the basic processes and investigating treatment possibilities, this review provides a crucial resource for scientists and medical practitioners, aiding in a deep understanding of ferroptosis and its effects in various disease situations.

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“…Excessive iron leads to a decrease in insulin secretion in MIN6-β cells, which is attributed to iron-induced oxidative stress and the down-regulation of synaptosomal associated protein 25 (SNAP25). Additionally, iron also disturbs the transcription of synaptotagmin 7 (SYT7), which is regulated by OGG1 [144]. Therefore, iron can disrupt the secretory pathway and attenuate insulin secretion [145].…”

Section: Iron and Glucose Metabolismmentioning

confidence: 99%

The Link between Trace Metal Elements and Glucose Metabolism: Evidence from Zinc, Copper, Iron, and Manganese-Mediated Metabolic Regulation

Sun,

Shao,

Yan

et al. 2023

Metabolites

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Trace metal elements are of vital importance for fundamental biological processes. They function in various metabolic pathways after the long evolution of living organisms. Glucose is considered to be one of the main sources of biological energy that supports biological activities, and its metabolism is tightly regulated by trace metal elements such as iron, zinc, copper, and manganese. However, there is still a lack of understanding of the regulation of glucose metabolism by trace metal elements. In particular, the underlying mechanism of action remains to be elucidated. In this review, we summarize the current concepts and progress linking trace metal elements and glucose metabolism, particularly for the trace metal elements zinc, copper, manganese, and iron.

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Excessive iron inhibits insulin secretion via perturbing transcriptional regulation of SYT7 by OGG1

Cited by 6 publications

References 48 publications

Single-Nucleotide Polymorphisms in Base-Excision Repair-Related Genes Involved in the Risk of an Occurrence of Non-Alcoholic Fatty Liver Disease

Single-Nucleotide Polymorphisms in Base-Excision Repair-Related Genes Involved in the Risk of an Occurrence of Non-Alcoholic Fatty Liver Disease

The mechanism of ferroptosis and its related diseases

The Link between Trace Metal Elements and Glucose Metabolism: Evidence from Zinc, Copper, Iron, and Manganese-Mediated Metabolic Regulation

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