scholarly journals Parental genomic imprinting in endocrinopathies

2002 ◽  
pp. 561-569 ◽  
Author(s):  
C Polychronakos ◽  
A Kukuvitis
Keyword(s):  
Type 1 Diabetes ◽  
Genomic Imprinting ◽  
Molecular Mechanisms ◽  
Neonatal Diabetes ◽  
Gene Copy ◽  
Imprinted Genes ◽  
Mrna Transcripts ◽  
Transient Neonatal Diabetes ◽  
Silver Russell Syndrome

Genomic imprinting is the phenomenon whereby some genes preferentially produce mRNA transcripts from the gene copy derived from the parent of a specific sex. It has been implicated in a number of human diseases (most of them of endocrine interest), such as Prader-Willi/Angelman syndromes, Silver-Russell syndrome, Beckwith-Wiedemann syndrome, transient neonatal diabetes, the focal form of nesidioblastosis, and pseudohypoparathyroidism. Involvement of imprinted genes affecting birth weight and causing susceptibility to type 1 diabetes is under investigation. Recent knowledge about the varied molecular mechanisms involved will be outlined.

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.

scholarly journals Glycosylation of CaV3.2 Channels Contributes to the Hyperalgesia in Peripheral Neuropathy of Type 1 Diabetes

2020 ◽  
Vol 14 ◽  
Author(s):  
Sonja Lj. Joksimovic ◽  
J. Grayson Evans ◽  
William E. McIntire ◽  
Peihan Orestes ◽  
Paula Q. Barrett ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Adult Female ◽  
Molecular Mechanisms ◽  
Sprague Dawley ◽  
Knock Out ◽  
Peripheral Diabetic Neuropathy ◽  
Novel Treatments

Our previous studies implicated glycosylation of the CaV3.2 isoform of T-type Ca2+ channels (T-channels) in the development of Type 2 painful peripheral diabetic neuropathy (PDN). Here we investigated biophysical mechanisms underlying the modulation of recombinant CaV3.2 channel by de-glycosylation enzymes such as neuraminidase (NEU) and PNGase-F (PNG), as well as their behavioral and biochemical effects in painful PDN Type 1. In our in vitro study we used whole-cell recordings of current-voltage relationships to confirm that CaV3.2 current densities were decreased ~2-fold after de-glycosylation. Furthermore, de-glycosylation induced a significant depolarizing shift in the steady-state relationships for activation and inactivation while producing little effects on the kinetics of current deactivation and recovery from inactivation. PDN was induced in vivo by injections of streptozotocin (STZ) in adult female C57Bl/6j wild type (WT) mice, adult female Sprague Dawley rats and CaV3.2 knock-out (KO mice). Either NEU or vehicle (saline) were locally injected into the right hind paws or intrathecally. We found that injections of NEU, but not vehicle, completely reversed thermal and mechanical hyperalgesia in diabetic WT rats and mice. In contrast, NEU did not alter baseline thermal and mechanical sensitivity in the CaV3.2 KO mice which also failed to develop painful PDN. Finally, we used biochemical methods with gel-shift analysis to directly demonstrate that N-terminal fragments of native CaV3.2 channels in the dorsal root ganglia (DRG) are glycosylated in both healthy and diabetic animals. Our results demonstrate that in sensory neurons glycosylation-induced alterations in CaV3.2 channels in vivo directly enhance diabetic hyperalgesia, and that glycosylation inhibitors can be used to ameliorate painful symptoms in Type 1 diabetes. We expect that our studies may lead to a better understanding of the molecular mechanisms underlying painful PDN in an effort to facilitate the discovery of novel treatments for this intractable disease.

scholarly journals ER stress and development of type 1 diabetes

2016 ◽  
Vol 64 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Feyza Engin
Keyword(s):  
Type 1 Diabetes ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Adaptive Responses ◽  
Β Cell ◽  
Cellular Homeostasis ◽  
Unfolded Protein

Type 1 diabetes (T1D) results from an autoimmune-mediated destruction of pancreatic β cells. The incidence of T1D is on the rise globally around 3% to 5% per year and rapidly increasing incidence in younger children is of the greatest concern. currently, there is no way to cure or prevent T1D; hence, a deeper understanding of the underlying molecular mechanisms of this disease is essential to the development of new effective therapies. The endoplasmic reticulum (ER) is an organelle with multiple functions that are essential for cellular homeostasis. Excessive demand on the ER, chronic inflammation, and environmental factors lead to ER stress and to re-establish cellular homeostasis, the adaptive unfolded protein response (UPR) is triggered. However, chronic ER stress leads to a switch from a prosurvival to a proapoptotic UPR, resulting in cell death. Accumulating data have implicated ER stress and defective UPR in the pathogenesis of inflammatory and autoimmune diseases, and ER stress has been implicated in β-cell failure in type 2 diabetes. However, the role of ER stress and the UPR in β-cell pathophysiology and in the initiation and propagation of the autoimmune responses in T1D remains undefined. This review will highlight the current understanding and recent in vivo data on the role of ER stress and adaptive responses in T1D pathogenesis and the potential therapeutic aspect of enhancing β-cell ER function and restoring UPR defects as novel clinical strategies against this disease.

MicroRNAs and Diabetes Mellitus Type 1

2021 ◽  
Vol 17 ◽  
Author(s):  
Farbod Bahreini ◽  
Elham Rayzan ◽  
Nima Rezaei
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Early Detection ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Islet Cells ◽  
Diabetes Mellitus Type 1 ◽  
Complementary Sequence ◽  
Multiple Organs

: Type 1 diabetes mellitus is a multifactorial, progressive, autoimmune disease with a strong genetic feature that can affect multiple organs, including kidney, eyes, and nerves. Early detection of type 1 diabetes can help critically to avoid serious damages to these organs. MicroRNAs are small RNA molecules that act in post-transcriptional gene regulation by attaching to the complementary sequence in the 3'-untranslated region of their target genes. Alterations in the expression of microRNA coding genes are extensively reported in several diseases such as type 1 diabetes. Presenting non-invasive biomarkers for early detection of type 1 diabetes by quantifying microRNAs gene expression level can be an influential step in biotechnology and medicine. This review discusses the area of microRNAs dysregulation in type 1 diabetes and affected molecular mechanisms involved in pancreatic islet cells formation and dysregulation in the expression of inflammatory elements as well as pro-inflammatory cytokines.

scholarly journals Type 1 diabetes can present before the age of 6 months and is characterised by autoimmunity and rapid loss of beta cells

Diabetologia ◽  
2020 ◽  
Vol 63 (12) ◽  
pp. 2605-2615 ◽  
Author(s):  
Matthew B. Johnson ◽  
◽  
Kashyap A. Patel ◽  
Elisa De Franco ◽  
William Hagopian ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Secretion ◽  
Genetic Risk ◽  
Early Onset ◽  
Genetic Risk Score ◽  
Neonatal Diabetes ◽  
Pathogenic Variant ◽  
Rapid Loss ◽  
C Peptide

Abstract Aims/hypothesis Diabetes diagnosed at <6 months of age is usually monogenic. However, 10–15% of affected infants do not have a pathogenic variant in one of the 26 known neonatal diabetes genes. We characterised infants diagnosed at <6 months of age without a pathogenic variant to assess whether polygenic type 1 diabetes could arise at early ages. Methods We studied 166 infants diagnosed with type 1 diabetes at <6 months of age in whom pathogenic variants in all 26 known genes had been excluded and compared them with infants with monogenic neonatal diabetes (n = 164) or children with type 1 diabetes diagnosed at 6–24 months of age (n = 152). We assessed the type 1 diabetes genetic risk score (T1D-GRS), islet autoantibodies, C-peptide and clinical features. Results We found an excess of infants with high T1D-GRS: 38% (63/166) had a T1D-GRS >95th centile of healthy individuals, whereas 5% (8/166) would be expected if all were monogenic (p < 0.0001). Individuals with a high T1D-GRS had a similar rate of autoantibody positivity to that seen in individuals with type 1 diabetes diagnosed at 6–24 months of age (41% vs 58%, p = 0.2), and had markedly reduced C-peptide levels (median <3 pmol/l within 1 year of diagnosis), reflecting rapid loss of insulin secretion. These individuals also had reduced birthweights (median z score −0.89), which were lowest in those diagnosed with type 1 diabetes at <3 months of age (median z score −1.98). Conclusions/interpretation We provide strong evidence that type 1 diabetes can present before the age of 6 months based on individuals with this extremely early-onset diabetes subtype having the classic features of childhood type 1 diabetes: high genetic risk, autoimmunity and rapid beta cell loss. The early-onset association with reduced birthweight raises the possibility that for some individuals there was reduced insulin secretion in utero. Comprehensive genetic testing for all neonatal diabetes genes remains essential for all individuals diagnosed with diabetes at <6 months of age.

scholarly journals Organ-Based Response to Exercise in Type 1 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Lisa Stehno-Bittel
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Tissue Level ◽  
Significant Research ◽  
Response To Exercise ◽  
Increased Activity

While significant research has clearly identified sedentary behavior as a risk factor for type 2 diabetes and its subsequent complications, the concept that inactivity could be linked to the complications associated with type 1 diabetes (T1D) remains underappreciated. This paper summarizes the known effects of exercise on T1D at the tissue level and focuses on the pancreas, bone, the cardiovascular system, the kidneys, skeletal muscle, and nerves. When possible, the molecular mechanisms underlying the benefits of exercise for T1D are elucidated. The general benefits of increased activity on health and the barriers to increased exercise specific to people with T1D are discussed.

scholarly journals Metallothionein expression in slow- vs. fast-twitch muscle fibers following 4 weeks of streptozotocin-induced type 1 diabetes

FACETS ◽  
2018 ◽  
Vol 3 (1) ◽  
pp. 315-325 ◽  
Author(s):  
Pamela Mondragon ◽  
Andreas Bergdahl
Keyword(s):  
Oxidative Stress ◽  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Protein Carbonyl ◽  
Glucose Levels ◽  
Significant Difference ◽  
Streptozotocin Induced Diabetes ◽  
Carbonyl Formation ◽  
Fast Twitch

Type 1 diabetes (T1DM) is known to cause an increase in reactive oxygen species (ROS) and elevated intracellular glucose levels. We investigated the metallothionein I and II (MT I+II) antioxidants expression in soleus (mainly slow-twitch) and plantaris (predominantly fast-twitch) skeletal muscle using a rodent model of streptozotocin-induced diabetes. The presence of oxidative stress was confirmed by the detection of increased levels of protein carbonyl formation in the diabetic tissues. DAB (3,3′-diaminobenzidine) immunostaining and Western blotting analyses demonstrated that MT I+II expression was significantly upregulated in the diabetic soleus and plantaris muscle tissues compared with their respective controls. Moreover, no significant difference was detected between the plantaris and soleus controls or between the plantaris and soleus diabetic tissues. These findings suggest that there is an increase in MT protein expression in the soleus and plantaris muscles associated with the induction of T1DM. A better understanding of the molecular mechanisms that allow MT to prevent the oxidative stress associated with diabetes could lead to a novel therapeutic strategy for this chronic disease and its associated complications.

scholarly journals Integrative Analyses of Genes Associated with Fulminant Type 1 Diabetes

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiaofeng Ye ◽  
Tianshu Zeng ◽  
Wen Kong ◽  
Lu-lu Chen
Keyword(s):  
Type 1 Diabetes ◽  
Gene Network ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Healthy Controls ◽  
Ppi Network ◽  
Hub Genes ◽  
Fulminant Type 1 Diabetes ◽  
Fulminant Type

Objective. Fulminant type 1 diabetes (FT1D) is a type of type 1 diabetes, which is characterized by rapid onset of disease and severe metabolic disorders. We intend to screen for crucial genes and potential molecular mechanisms in FT1D in this study. Method. We downloaded GSE44314, which includes six healthy controls and five patients with FT1D, from the GEO database. Identification of differentially expressed genes (DEGs) was performed by NetworkAnalyst. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were screened by an online tool—Database for Annotation, Visualization, and Integration Discovery (DAVID). Protein-protein interaction (PPI) network and hub genes among DEGs were analyzed by NetworkAnalyst. And we also use NetworkAnalyst to find out the microRNAs (miRNAs) and transcription factors (TFs) which regulate the expression of DEGs. Result. We identified 130 DEGs (60 upregulated and 70 downregulated DEGs) between healthy controls and FT1D patients. GO analysis results revealed that DEGs were mostly enriched in generation of precursor metabolites and energy, neurohypophyseal hormone activity, and mitochondrial inner membrane. KEGG pathway analysis demonstrated that DEGs were mostly involved in nonalcoholic fatty liver disease. Results indicated that NCOA1, SRF, ERBB3, EST1, TOP1, UBE2S, INO80, COX7C, ITGAV, and COX6C were the top hub genes in the PPI network. Furthermore, we recognized that LDLR, POTEM, IFNAR2, BAZ2A, and SRF were the top hub genes in the miRNA-target gene network, and SRF, TSPAN4, CD59, ETS1, and SLC25A25 were the top hub genes in the TF-target gene network. Conclusion. Our study pinpoints key genes and pathways associated with FT1D by a sequence of bioinformatics analysis on DEGs. These identified genes and pathways provide more detailed molecular mechanisms of FT1D and may provide novel therapeutic targets.

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