Hyperglycemic memory in metabolism and cancer

2016 ◽  
Vol 26 (2) ◽  
Author(s):  
Changhu Lee ◽  
Dohyeon An ◽  
Jiyoung Park
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Expression Profiles ◽  
Strong Association ◽  
Gene Expression Profiles ◽  
Metabolic Memory ◽  
Target Cells ◽  
Diabetic Patients

AbstractHyperglycemia is a hallmark of both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Recent evidence strongly suggests that prolonged exposure to hyperglycemia can epigenetically modify gene expression profiles in human cells and that this effect is sustained even after hyperglycemic control is therapeutically achieved; this phenomenon is called hyperglycemic memory. This metabolic memory effect contributes substantially to the pathology of various diabetic complications, such as diabetic retinopathy, hypertension, and diabetic nephropathy. Due to the metabolic memory in cells, diabetic patients suffer from various complications, even after hyperglycemia is controlled. With regard to this strong association between diabetes and cancer risk, cancer cells have emerged as key target cells of hyperglycemic memory in diabetic cancer patients. In this review, we will discuss the recent understandings of the molecular mechanisms underlying hyperglycemic memory in metabolism and cancer.

scholarly journals Autoantibodies to thyroid peroxidase in patients with type 1 diabetes in Taiwan

1998 ◽  
pp. 44-48 ◽  
Author(s):  
CC Chang ◽  
CN Huang ◽  
LM Chuang
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Thyroid Autoimmunity ◽  
Strong Association ◽  
Thyroid Peroxidase ◽  
Diabetic Patients ◽  
Significant Difference ◽  
Type 1 Diabetic Patients

OBJECTIVE: Type 1 diabetes mellitus is frequently associated with autoimmune thyroid disease (ATD). Genetic susceptibility to autoantibody formation in association with ATD and type 1 diabetes mellitus has been described with varying frequencies, but there is still debate about the situation in the Chinese population. We have, therefore, investigated the prevalence of anti-thyroid peroxidase (anti-TPO) in type 1 diabetic patients, and compared the effect of anti-glutamate decarboxylase (anti-GAD) on the thyroid autoimmunity in patients with type 1 diabetes mellitus in Taiwan. SUBJECTS AND METHODS: Two hundred and forty-three subjects with type 1 diabetes mellitus and seventy unrelated normal controls were recruited for the detection of anti-TPO. Two hundred and seventeen sera from two hundred and forty-three type 1 diabetic patients were tested for anti-GAD. RIA and immunoprecipitation were used for anti-TPO and anti-GAD detection respectively. RESULTS: The intra-assay and interassay coefficients of variation of anti-TPO detected by the RIA method ranged from 5.5% to 11.1%. Among 243 type 1 diabetic patients, 53 (21.8%) were positive for anti-TPO. Compared with those without thyroid autoimmunity, there was a female preponderance for the type 1 diabetic patients with thyroid autoimmunity (female:male, 99:91 vs 37:16 respectively). Among the type 1 diabetic patients with thyroid autoimmunity, anti-TPO tended to occur in those of older age or with long-standing disease. The frequency of anti-GAD was 45.6%, (99 of 217), without gender preponderance (males:females, 18.0% vs 27.61%). Compared with those with negative anti-GAD, no significant difference of anti-TPO positivity for the type 1 diabetic patients with positive anti-GAD was found. CONCLUSION: Our data indicated that the RIA method for anti-TPO detection is sensitive and precise for routine clinical use. The presence of anti-TPO in 21.8% of our type 1 diabetic patients confirmed the strong association of ATD and type 1 diabetes mellitus without ethnic differences. The absence of correlation between anti-TPO and anti-GAD in our type 1 diabetic patients suggested genetic heterogeneity in the role of autoimmunity of type 1 diabetes mellitus and ATD among races.

scholarly journals Association of the polymorphous marker G6230A of the CTLA4 gene with type 1 diabetes mellitus in the patients of Russian descent

2012 ◽  
Vol 58 (4) ◽  
pp. 14-17
Author(s):  
O I Kopylova ◽  
T L Kuraeva ◽  
E Iu Lavrikova ◽  
E V Titovich ◽  
A G Nikitin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Healthy Subjects ◽  
Molecular Mechanisms ◽  
Control Group ◽  
Diabetic Patients ◽  
Potential Candidate ◽  
Ctla4 Gene

The risk of devolvement of type 1 diabetes mellitus (DM1) remains a challenging problem because neither etiology of the disease nor its prognosis and genetic predisposition to this condition are clearly understood. The development of any autoimmune process starts from the disturbance of subtle molecular mechanisms involved in the regulation of the immune system. Therefore, the genes controlling the function of its major components are at the same time the potential candidate genes encoding for the predisposition to DM1. Their association with the disease was studied by means of comparative analysis of the frequency distribution of alleles and genotypes of the polymorphous rs3087243 (G6230A) marker of the CTLA4 gene encoding for antigen-4 of cytotoxic T-lymphocytes. The present study included 257 patients presenting with type 1 diabetes mellitus and 526 healthy subjects. Genotypes were identified by the "real time" amplification technique. The AA genotype was found to occur less frequently in the diabetic patients than in the control group (11.3% and 22.1% respectively). In contrast, the frequency of the GG genotype was higher in the patients with DM1 than in the healthy subjects (44.7% and 37.5% respectively). It is concluded that the polymorphous rs3087243 marker of the CTLA4 gene is significantly associated with the predisposition to the development of type 1 diabetes mellitus in the patients of Russian descent.

scholarly journals Pancreatic Beta Cell Death: Novel Potential Mechanisms in Diabetes Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-19 ◽  
Author(s):  
Joselyn Rojas ◽  
Valmore Bermudez ◽  
Jim Palmar ◽  
María Sofía Martínez ◽  
Luis Carlos Olivar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Death ◽  
Beta Cell ◽  
Molecular Mechanisms ◽  
Pancreatic Beta Cell ◽  
Diabetic Patients ◽  
Pathophysiological Mechanism ◽  
Islet Amyloid ◽  
Beta Cell Death

Purpose of Review. Describing the diverse molecular mechanisms (particularly immunological) involved in the death of the pancreatic beta cell in type 1 and type 2 diabetes mellitus. Recent Findings. Beta cell death is the final event in a series of mechanisms that, up to date, have not been entirely clarified; it represents the pathophysiological mechanism in the natural history of diabetes mellitus. These mechanisms are not limited to an apoptotic process only, which is characteristic of the immune-mediated insulitis in type 1 diabetes mellitus. They also include the action of proinflammatory cytokines, the production of reactive oxygen species, DNA fragmentation (typical of necroptosis in type 1 diabetic patients), excessive production of islet amyloid polypeptide with the consequent endoplasmic reticulum stress, disruption in autophagy mechanisms, and protein complex formation, such as the inflammasome, capable of increasing oxidative stress produced by mitochondrial damage. Summary. Necroptosis, autophagy, and pyroptosis are molecular mechanisms that modulate the survival of the pancreatic beta cell, demonstrating the importance of the immune system in glucolipotoxicity processes and the potential role for immunometabolism as another component of what once known as the “ominous octet.”

Gene Expression Profiles Stratified according to Type 1 Diabetes Mellitus Susceptibility Regions

2008 ◽  
Vol 1150 (1) ◽  
pp. 282-289 ◽  
Author(s):  
Diane Meyre Rassi ◽  
Cristina Moraes Junta ◽  
Ana Lúcia Fachin ◽  
Paula Sandrin-Garcia ◽  
Stephano Mello ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Iron Chelator ◽  
Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

scholarly journals The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

2021 ◽  
Vol 22 (2) ◽  
pp. 803
Author(s):  
Giuseppina Emanuela Grieco ◽  
Noemi Brusco ◽  
Giada Licata ◽  
Daniela Fignani ◽  
Caterina Formichi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Β Cell ◽  
Physiological Mechanisms ◽  
Effective Strategies ◽  
Chronic Hyperglycaemia ◽  
Shed Light

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.

scholarly journals Coaggregation of Asthma and Type 1 Diabetes in Children: A Narrative Review

2021 ◽  
Vol 22 (11) ◽  
pp. 5757
Author(s):  
Laura Sgrazzutti ◽  
Francesco Sansone ◽  
Marina Attanasi ◽  
Sabrina Di Pillo ◽  
Francesco Chiarelli
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Narrative Review ◽  
T Helper ◽  
Children With Asthma ◽  
Potential Link ◽  
Th 1 ◽  
Th1 And Th2

Asthma and type 1 diabetes mellitus (T1DM) are two of the most frequent chronic diseases in children, representing a model of the atopic and autoimmune diseases respectively. These two groups of disorders are mediated by different immunological pathways, T helper (Th)1 for diabetes and Th2 for asthma. For many years, these two groups were thought to be mutually exclusive according to the Th1/Th2 paradigm. In children, the incidence of both diseases is steadily increasing worldwide. In this narrative review, we report the evidence of the potential link between asthma and T1DM in childhood. We discuss which molecular mechanisms could be involved in the link between asthma and T1DM, such as genetic predisposition, cytokine patterns, and environmental influences. Cytokine profile of children with asthma and T1DM shows an activation of both Th1 and Th2 pathways, suggesting a complex genetic-epigenetic interaction. In conclusion, in children, the potential link between asthma and T1DM needs further investigation to improve the diagnostic and therapeutic approach to these patients. The aim of this review is to invite the pediatricians to consider the potential copresence of these two disorders in clinical practice.

Corneal Sensitivity in Bacterial Keratitis Patients with or without Diabetes Mellitus

2021 ◽  
pp. 67-72
Author(s):  
O. V. Zavoloka
Keyword(s):  
Diabetes Mellitus ◽  
Anterior Segment ◽  
Control Group ◽  
Sensitivity Threshold ◽  
Diabetic Patients ◽  
Bacterial Keratitis ◽  
Corneal Sensitivity ◽  
Fellow Eye ◽  
Nondiabetic Control

The aim. To identify the features of corneal sensitivity of the sick and the fellow eye in bacterial keratitis patients with or without diabetes mellitus. Materials and methods. The analysis was performed on the basis of survey data of 62 type 1 diabetes patients with bacterial keratitis and 43 nondiabetic control patients with bacterial keratitis. The examination was performed at the first visit. In addition to standard ophthalmic examination, the patients underwent fluorescein test, OCT of the anterior segment of the eye, non-contact corneal aesthesiometry. Results and discussion. The average corneal sensitivity threshold in diabetic patients with bacterial keratitis at the first visit at all air flow temperatures exceeded the corresponding indicators in nondiabetic patients of the control group: by 33.5% at an air temperature of 5 °C, by 30.6% at 15 °C, by 28.8% at 20 °C, by 27% at 30 °C, and by 26.1% at 40 °C (p<0.05). The average corneal sensitivity threshold at a temperature of 20 °C in the fellow eye in diabetic patients with bacterial keratitis exceeded that in nondiabetic patients with bacterial keratitis of the control group by 32.9 % (p<0.05). Conclusions. Corneal sensitivity of the sick and fellow eye in patients with bacterial keratitis depends on the presence of diabetes mellitus. The average threshold of corneal sensitivity of the sick and fellow eye in diabetic patients with bacterial keratitis at the first visit exceeds the corresponding values in nondiabetic patients with bacterial keratitis. Keywords: diabetes mellitus, bacterial keratitis, corneal sensitivity.

Dorsal Root Ganglion Neuron Types and Their Functional Specialization

2018 ◽  
pp. 127-155 ◽  
Author(s):  
Edward C. Emery ◽  
Patrik Ernfors
Keyword(s):  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Drg Neurons ◽  
Low Threshold

Primary sensory neurons of the dorsal root ganglion (DRG) respond and relay sensations that are felt, such as those for touch, pain, temperature, itch, and more. The ability to discriminate between the various types of stimuli is reflected by the existence of specialized DRG neurons tuned to respond to specific stimuli. Because of this, a comprehensive classification of DRG neurons is critical for determining exactly how somatosensation works and for providing insights into cell types involved during chronic pain. This article reviews the recent advances in unbiased classification of molecular types of DRG neurons in the perspective of known functions as well as predicted functions based on gene expression profiles. The data show that sensory neurons are organized in a basal structure of three cold-sensitive neuron types, five mechano-heat sensitive nociceptor types, four A-Low threshold mechanoreceptor types, five itch-mechano-heat–sensitive nociceptor types and a single C–low-threshold mechanoreceptor type with a strong relation between molecular neuron types and functional types. As a general feature, each neuron type displays a unique and predicable response profile; at the same time, most neuron types convey multiple modalities and intensities. Therefore, sensation is likely determined by the summation of ensembles of active primary afferent types. The new classification scheme will be instructive in determining the exact cellular and molecular mechanisms underlying somatosensation, facilitating the development of rational strategies to identify causes for chronic pain.

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