Insights into the Role of DNA Methylation and Protein Misfolding in Diabetes Mellitus

2019 ◽  
Vol 19 (6) ◽  
pp. 744-753 ◽  
Author(s):  
Sara M. Ahmed ◽  
Dina Johar ◽  
Mohamed Medhat Ali ◽  
Nagwa El-Badri
Keyword(s):  
Diabetes Mellitus ◽  
Dna Methylation ◽  
Protein Function ◽  
Protein Misfolding ◽  
Gene Sequence ◽  
Metabolic Memory ◽  
Treatment Of Diabetes

Background: Diabetes mellitus is a metabolic disorder that is characterized by impaired glucose tolerance resulting from defects in insulin secretion, insulin action, or both. Epigenetic modifications, which are defined as inherited changes in gene expression that occur without changes in gene sequence, are involved in the etiology of diabetes. Methods: In this review, we focused on the role of DNA methylation and protein misfolding and their contribution to the development of both type 1 and type 2 diabetes mellitus. Results: Changes in DNA methylation in particular are highly associated with the development of diabetes. Protein function is dependent on their proper folding in the endoplasmic reticulum. Defective protein folding and consequently their functions have also been reported to play a role. Early treatment of diabetes has proven to be of great benefit, as even transient hyperglycemia may lead to pathological effects and complications later on. This has been explained by the theory of the development of a metabolic memory in diabetes. The basis for this metabolic memory was attributed to oxidative stress, chronic inflammation, non-enzymatic glycation of proteins and importantly, epigenetic changes. This highlights the importance of linking new therapeutics targeting epigenetic mechanisms with traditional antidiabetic drugs. Conclusion: Although new data is evolving on the relation between DNA methylation, protein misfolding, and the etiology of diabetes, more studies are required for developing new relevant diagnostics and therapeutics.

scholarly journals Gut microbiota imbalances in Tunisian participants with type 1 and type 2 diabetes mellitus

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Meriem Fassatoui ◽  
Mireia Lopez-Siles ◽  
Diana A. Díaz-Rizzolo ◽  
Haifa Jmel ◽  
Chokri Naouali ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Multivariate Analysis ◽  
Gut Microbiota ◽  
Glycated Hemoglobin ◽  
Statistical Tests ◽  
Treatment Of Diabetes

Abstract Gut microbiota plays an important role in the regulation of the immune system and host’s metabolism. We aimed to characterize the gut microbiota of Tunisian participants with and without diabetes. We enrolled ten participants with type 1 diabetes mellitus (T1DM), ten patients with type 2 diabetes mellitus (T2DM), and 11 subjects without diabetes. Bacteria was quantified in fecal samples by quantitative PCR (qPCR). Statistical tests and multivariate analysis were performed using RStudio program. Results showed that the proportions of Firmicutes, Akkermansia muciniphila, and Faecalibacterium prausnitzii (P≤0.041), as well as, the ratio Firmicutes/Bacteroidetes decreased in participants with T1DM compared with those without diabetes (p = 0.036). Participants with T2DM presented a reduction in the amounts of A. muciniphila and F. prausnitzii compared with those without diabetes (P≤0.036). Furthermore, A muciniphila is negatively correlated with glucose level (P=0.022) and glycated hemoglobin (HbA1c) (P=0.035). Multivariate analysis revealed that participants with diabetes formed a cluster apart compared with those without diabetes. In conclusion the gut bacteria of Tunisian participants with diabetes was altered. The gut bacterial profile, especially the distribution of A muciniphila in participants with diabetes was affected by glycemic dysregulation. The investigation of the gut microbiota may help clinicians to improve diagnosis and treatment of diabetes and its complications.

scholarly journals The role of epigenetics in the pathology of diabetic complications

2010 ◽  
Vol 299 (1) ◽  
pp. F14-F25 ◽  
Author(s):  
Louisa M. Villeneuve ◽  
Rama Natarajan
Keyword(s):  
Diabetic Complications ◽  
Animal Studies ◽  
Microvascular Complications ◽  
Treatment Options ◽  
Metabolic Memory ◽  
Epigenetic Changes ◽  
Methylation Patterns

Diabetes is associated with significantly accelerated rates of several debilitating microvascular complications such as nephropathy, retinopathy, and neuropathy, and macrovascular complications such as atherosclerosis and stroke. While several studies have been devoted to the evaluation of genetic factors related to type 1 and type 2 diabetes and associated complications, much less is known about epigenetic changes that occur without alterations in the DNA sequence. Environmental factors and nutrition have been implicated in diabetes and can also affect epigenetic states. Exciting research has shown that epigenetic changes in chromatin can affect gene transcription in response to environmental stimuli, and changes in key chromatin histone methylation patterns have been noted under diabetic conditions. Reports also suggest that epigenetics may be involved in the phenomenon of metabolic memory observed in clinic trials and animal studies. Further exploration into epigenetic mechanisms can yield new insights into the pathogenesis of diabetes and its complications and uncover potential therapeutic targets and treatment options to prevent the continued development of diabetic complications even after glucose control has been achieved.

scholarly journals NPH insulin. Effective mixing - effective dose regimen

2011 ◽  
Vol 57 (4) ◽  
pp. 56-60
Author(s):  
T V Nikonova
Keyword(s):  
Diabetes Mellitus ◽  
High Performance ◽  
Insulin Dose ◽  
Nph Insulin ◽  
Marked Variability ◽  
Wide Availability ◽  
Treatment Of Diabetes ◽  
Attending Physician

Insulin therapy, a corner stone of the treatment of diabetes mellitus, both type 1 and type 2, has undergone substantial modification since the manufacture of the first insulin preparations 90 years ago up to the present time. Human insulins, such as neutral protamin Hagedorn (NPH) insulins, remain a major instrument of therapy of diabetes mellitus despite rapid developments in this field of knowledge and the wide availability of insulin analogs. When prescribing these preparations, the attending physician should be absolutely confident that the patient has a minimum background of knowledge and skills indispensable for efficacious and safe treatment. Such skills include the habit of mixing NPH insulin suspensions by 20-fold turning the vial or the cartridge upside-down or rolling them between the palms in order to ensure the uniform distribution of insulin in the suspension and its accurate dosing. The manufactures place from one to three glass or metal bullets inside the vials and cartridges for more homogeneous mixing of their contents. P. Kaiser et al. undertook the study of several pharmaceutical forms of NPH insulin manufactured by different companies to estimate the accuracy of dosing (variability of the insulin dose depending on the number of turns of the cartridge for homogeneous mixing). The insulin concentration in a single dose was measured by high-performance liquid chromatography. Marked variability of the insulin dose after less than ten (three or six) turns was documented for all cartridges with the exception of Insuman Basal insulin cartridges ("Sanofi"). It may be expected that the accuracy of dosing will not deteriorate using these cartridges owing to the presence in them of three heavy metal bullets even if the patient does not perform the necessary mixing procedure for one or another reason.

Role of vasopressin signaling in the pathogenesis of diabetic nephropathy

2021 ◽  
pp. 9-20
Author(s):  
Arus Garikovna Margaryan ◽  
Svetlana Anatolievna Lebedeva ◽  
Dariya Mikhailovna Lisitsyna ◽  
Polina Igorevna Sirotkina ◽  
Lyudmila Aleksandrovna Yakubova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Major Complication ◽  
Epidemiological Studies ◽  
Animal Models Of Diabetes

The diabetic kidney disease (also known as diabetic nephropathy) is a major complication of diabetes mellitus and also the most common cause of chronic kidney disease. Elevated plasma levels of vasopressin are consistently observed in patients with either type 1 and type 2 diabetes mellitus and in animal models of diabetes mellitus. A role of enhanced vasopressin signaling in progression of the diabetic nephropathy to chronic kidney disease has been suggested in several epidemiological studies but the underlying pathogenetic mechanisms remain largely unclear and are the subject of current scientific research.

scholarly journals Diabetes Cognitive Impairments and the Effect of Traditional Chinese Herbs

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaohan Xu ◽  
Leilei Guo ◽  
Guoqing Tian
Keyword(s):  
Risk Factors ◽  
Cognitive Impairments ◽  
Chinese Herbs ◽  
Vascular Risk ◽  
Insulin Deficiency ◽  
Chinese Herbal ◽  
Treatment Of Diabetes

The problem of cognitive impairment resulting from diabetes is gaining more acceptance and attention. Both type 1 and type 2 diabetes mellitus have been proved to be associated with reduced performance on numerous domains of cognitive function. Although the exact mechanisms of cognitive impairments in diabetes have not been completely understood, hyperglycemia and insulin resistance seem to play significant roles. And other possible risk factors such as hypoglycemia, insulin deficiency, vascular risk factors, hyperactive HPA axis, depression, and altered neurotransmitters will also be examined. In the meanwhile, this review analyzed the role of the active ingredient of Chinese herbal medicine in the treatment of diabetes cognitive impairments.

scholarly journals The protean role of haptoglobin and haptoglobin genotypes on vascular complications in diabetes mellitus

2018 ◽  
Vol 25 (14) ◽  
pp. 1502-1519 ◽  
Author(s):  
Rinkoo Dalan ◽  
Goh Liuh Ling
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin E ◽  
Clinical Studies ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Diabetes Patients

Introduction and background Haptoglobin (Hp) is considered to be an antioxidant and protective against cardiovascular complications. Polymorphisms in the Hp gene interact with diabetes mellitus to affect the risk of vascular complications. Methods We review the updated literature about the protean role of Hp and Hp genotypes spanning genomics, molecular, translational and clinical studies. We searched Pubmed, SCOPUS and Google Scholar for all articles using the keywords: haptoglobin and/or haptoglobin polymorphism and diabetes. We review the diverse Hp genotypes, phenotypes and the impact on diabetes complications, including lessons from animal models and in vitro models. We describe the clinical studies on the associations of Hp genotypes with vascular complications in type 1 and type 2 diabetes comprehensively. We review the studies looking at vitamin E supplementation in a personalized manner in Hp2-2 diabetes individuals. Results and conclusion Hp genotypes have evolved as a result of deletions in the traditional Hp genes. The Hp genotypes have been associated with microvascular and macrovascular complications in type 1 diabetes mellitus but the association in type 2 diabetes is more consistent with cardiovascular complications. A preferential benefit of vitamin E and other antioxidants in the Hp2-2 genotype for cardiovascular complications in type 2 diabetes has been seen presumably secondary to interaction with high-density lipoprotein function. Hence, the Hp genotype can be used to personalize antioxidant therapeutics in diabetes patients. These results need to be corroborated in large, global, pragmatic, prospective, cardiovascular outcome trials in type 2 diabetes patients.

scholarly journals Hypertriglyceridemia in Diabetes Mellitus: Implications for Pediatric Care

2018 ◽  
Vol 2 (6) ◽  
pp. 497-512 ◽  
Author(s):  
Jacob C Hartz ◽  
Sarah de Ferranti ◽  
Samuel Gidding
Keyword(s):  
Diabetes Mellitus ◽  
Children And Adolescents ◽  
Pediatric Care ◽  
Poor Control ◽  
Atherogenic Lipid Profile ◽  
Increased Risk ◽  
Atherogenic Lipid

Abstract Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). It is estimated that the risk of CVD in diabetes mellitus (DM) is 2 to 10 times higher than in the general population. Much of this increased risk is thought to be related to the development of an atherogenic lipid profile, in which hypertriglyceridemia is an essential component. Recent studies suggest that dyslipidemia may be present in children and adolescents with DM, particularly in T2DM and in association with poor control in T1DM. However, the role of hypertriglyceridemia in the development of future CVD in youth with DM is unclear, as data are scarce. In this review, we will evaluate the pathophysiology of atherogenic hypertriglyceridemia in DM, the evidence regarding an independent role of triglycerides in the development of CVD, and the treatment of hypertriglyceridemia in patients with DM, highlighting the potential relevance to children and the need for more data in children and adolescents to guide clinical practice.

scholarly journals Role of platelet-derived growth factor in type II diabetes mellitus and its complications

2020 ◽  
Vol 17 (4) ◽  
pp. 147916412094211
Author(s):  
Sihong Shen ◽  
Fuyan Wang ◽  
Alejandra Fernandez ◽  
Weining Hu
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factors ◽  
Type Ii Diabetes ◽  
Critical Role ◽  
Type Ii Diabetes Mellitus ◽  
Regulate Cell Growth ◽  
Treatment Of Diabetes ◽  
Diabetes Development

Type 2 diabetes mellitus is a type of metabolic disorder characterized by hyperglycaemia with multiple serious complications, such as diabetic neuropathies, diabetic nephropathy, diabetic retinopathy, and diabetic foot. Platelet-derived growth factors are growth factors that regulate cell growth and division, playing a critical role in diabetes and its harmful complications. This review focused on the cellular mechanism of platelet-derived growth factors and their receptors on diabetes development. Furthermore, we raise some proper therapeutic molecular targets for the treatment of diabetes and its complications.

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