Approaching Type 2 Diabetes Mellitus by Systems Biology

2009 ◽  
pp. 361-376
Author(s):  
Axel Rasche
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Systems Biology ◽  
Animal Models ◽  
High Throughput ◽  
Complex Disease ◽  
Current Knowledge ◽  
High Throughput Experimentation

We acquired new computational and experimental prospects to seek insight and cure for millions of afflicted persons with an ancient malady. Type 2 diabetes mellitus (T2DM) is a complex disease with a network of interactions among several tissues and a multifactorial pathogenesis. Research conducted in human and multiple animal models has strongly focused on genetics so far. High-throughput experimentation technics like microarrays provide new tools at hand to amend current knowledge. By integrating those results the aim is to develop a systems biology model assisting the diagnosis and treatment. Beside experimentation techniques and platforms or rather general concepts for a new term in biology and medicine this chapter joins the conceptions with a rather actual medical challenge. It outlines current results and envisions a possible alley to the comprehension of T2DM.

scholarly journals The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Gut Microbiome ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Potential Target ◽  
The Relationship

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

Animal Research for Type 2 Diabetes Mellitus, Its Limited Translation for Clinical Benefit, and the Way Forward

2018 ◽  
Vol 46 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Zeeshan Ali ◽  
P. Charukeshi Chandrasekera ◽  
John J. Pippin
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Animal Models ◽  
Animal Research ◽  
Therapeutic Options ◽  
Research Findings

Obesity and type 2 diabetes mellitus (T2DM) have reached pandemic proportions worldwide, and considerable research efforts have been dedicated to investigating disease pathology and therapeutic options. The two hallmark features of T2DM, insulin resistance and pancreatic dysfunction, have been studied extensively by using various animal models. Despite the knowledge acquired from such models, particularly mechanistic discoveries that sometimes mimic human T2DM mechanisms or pathways, many details of human T2DM pathogenesis remain unknown, therapeutic options remain limited, and a cure has eluded research. Emerging human data have raised concern regarding inter-species differences at many levels (e.g. in gene regulation, pancreatic cytoarchitecture, glucose transport, and insulin secretion regulation), and the subsequent impact of these differences on the clinical translation of animal research findings. Therefore, it is important to recognise and address the translational gap between basic animal-based research and the clinical advances needed to prevent and treat T2DM. The purpose of this report is to identify some limitations of T2DM animal research, and to propose how greater human relevance and applicability of hypothesis-driven basic T2DM research could be achieved through the use of human-based data acquisition at various biological levels. This report addresses how in vitro, in vivo and in silico technologies could be used to investigate particular aspects of human glucose regulation. We do not propose that T2DM animal research has been without value in the identification of mechanisms, pathways, or potential targets for therapies, nor do we claim that human-based methods can provide all the answers. We recognise that the ultimate goal of T2DM animal research is to identify ways to advance the prevention, recognition and treatment of T2DM in humans, but postulate that this is where the use of animal models falls short, despite decades of effort. The best way to achieve this goal is by prioritising human-centred research.

scholarly journals Pathophysiological Characteristics Linking Type 2 Diabetes Mellitus and Colorectal Neoplasia

2021 ◽  
pp. 509-522
Author(s):  
Tomas Grega ◽  
Gabriela Vojtechova ◽  
Monika Gregova ◽  
Miroslav Zavoral ◽  
Stepan Suchanek
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Current Knowledge ◽  
Colorectal Neoplasia ◽  
Pathophysiological Mechanisms ◽  
Chronic Hyperglycemia ◽  
Altered Glucose

A substantial body of literature has provided evidence that type 2 diabetes mellitus (T2DM) and colorectal neoplasia share several common factors. Both diseases are among the leading causes of death worldwide and have an increasing incidence. In addition to usual risk factors such as sedentary lifestyle, obesity, and family history, common pathophysiological mechanisms involved in the development of these diseases have been identified. These include changes in glucose metabolism associated with adipose tissue dysfunction including insulin resistance resulting to hyperinsulinemia and chronic hyperglycemia. In addition to altered glucose metabolism, abdominal obesity has been associated with accented carcinogenesis with chronic subclinical inflammation. An increasing number of studies have recently described the role of the gut microbiota in metabolic diseases including T2DM and the development of colorectal cancer (CRC). Due to the interconnectedness of different pathophysiological processes, it is not entirely clear which factor is crucial in the development of carcinogenesis in patients with T2DM. The aim of this work is to review the current knowledge on the pathophysiological mechanisms of colorectal neoplasia development in individuals with T2DM. Here, we review the potential pathophysiological processes involved in the onset and progression of colorectal neoplasia in patients with T2DM. Uncovering common pathophysiological characteristics is essential for understanding the nature of these diseases and may lead to effective treatment and prevention.

scholarly journals Adipose tissue immune cells in obesity, type 2 diabetes mellitus and cardiovascular diseases

2021 ◽  
Author(s):  
Anna Cinkajzlová ◽  
Milos Mraz ◽  
Martin Haluzik
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Cardiovascular Diseases ◽  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Systemic Circulation

Immune cells are an inseparable component of adipose tissue intimately involved in most of its functions. Physiologically, they regulate adipose tissue homeostasis, while in case of adipose tissue stress immune cells are able to change their phenotype, enhance their count and subsequently contribute to the development and maintenance of local adipose tissue inflammation. Immune cells are an important source of inflammatory cytokines and other pro-inflammatory products that further influence not only surrounding tissues, but via systemic circulation also the whole organism being thus one of the main factors responsible for the transition from simple obesity to associated metabolic and cardiovascular complications. The purpose of this review is to summarize current knowledge on different adipose tissue immune cell subsets and their role in the development of obesity, type 2 diabetes mellitus and cardiovascular diseases.

scholarly journals The efficacy and safety of Momordica charantia L. in animal models of type 2 diabetes mellitus; A systematic review and meta-analysis

2019 ◽  
Author(s):  
Emanuel L. Peter ◽  
Prakash B. Nagendrappa ◽  
Anita Kaligirwa ◽  
Patrick Engeu Ogwang ◽  
Crispin Duncan Sesaazi
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Animal Models ◽  
Publication Bias ◽  
Methodological Quality ◽  
Meta Analysis ◽  
Risk Of Bias

AbstractBackgroundMomordica charantia L. (Cucurbitaceae) has been used to control hyperglycemia in people with type 2 diabetes mellitus in Asia, South America, and Africa for decades. However, a meta-analysis of clinical trials confirmed very low-quality evidence of its efficacy. To potentially increase the certainty of evidence, we evaluated the effect of M. charantia L. in comparison with vehicle on glycemic control in animal models of type 2 diabetes mellitus.MethodsReview authors searched in MEDLINE, Web of Science, Scopus, and CINAHL databases without language restriction through April 2019. Two authors independently evaluated full texts, assessed the risk of bias, and extracted data. We analyzed the influence of study design and evidence of publication bias.ResultsThe review included 66 studies involving 1861 animals. They had a follow up between 7 and 90 days. Majority 29 (43.9%) used Wistar albino rats, and 37 (56.1%) used male animals. Thirty-two (48%) used an aqueous extract of fresh fruits. M. charantia L. reduced fasting plasma glucose (FPG) and glycosylated hemoglobin A1c in comparison to vehicle control (42 studies, 815 animals; SMD, −6.86 [95% CI; −7.95, −5.77], 3 studies, 59 animals; SMD; −7.76 [95%CI; −12.50, −3.01]) respectively. Magnitude of FPG was large in Wistar albino rat subgroup; SMD; −10.29, [95%CI; −12.55, −8.03]. Publication bias changed FPG to non-significant −2.46 SMD, [95%CI; - 5.10, 0.17]. We downgraded the evidence to moderate quality due to poor methodological quality, high risk of bias, unexplained heterogeneity, suspected publication bias, and lack of standardized dose.ConclusionM. charantia L. lowers elevated plasma glucose level in type 2 diabetes mellitus animal models. Publication bias and poor methodological quality call for future researches to focus on standardizing dose with chemical markers and provide measures to improve preclinical type 2 diabetes mellitus studies.Systematic review registration CRD42019119181

scholarly journals Can Epigenetics of Endothelial Dysfunction Represent the Key to Precision Medicine in Type 2 Diabetes Mellitus?

2019 ◽  
Vol 20 (12) ◽  
pp. 2949 ◽  
Author(s):  
Celeste Coco ◽  
Luca Sgarra ◽  
Maria Assunta Potenza ◽  
Carmela Nacci ◽  
Barbara Pasculli ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Environmental Factors ◽  
Precision Medicine ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Transcriptional Responses

In both developing and industrialized Countries, the growing prevalence of Type 2 Diabetes Mellitus (T2DM) and the severity of its related complications make T2DM one of the most challenging metabolic diseases worldwide. The close relationship between genetic and environmental factors suggests that eating habits and unhealthy lifestyles may significantly affect metabolic pathways, resulting in dynamic modifications of chromatin-associated proteins and homeostatic transcriptional responses involved in the progression of T2DM. Epigenetic mechanisms may be implicated in the complex processes linking environmental factors to genetic predisposition to metabolic disturbances, leading to obesity and type 2 diabetes mellitus (T2DM). Endothelial dysfunction represents an earlier marker and an important player in the development of this disease. Dysregulation of the endothelial ability to produce and release vasoactive mediators is recognized as the initial feature of impaired vascular activity under obesity and other insulin resistance conditions and undoubtedly concurs to the accelerated progression of atherosclerotic lesions and overall cardiovascular risk in T2DM patients. This review aims to summarize the most current knowledge regarding the involvement of epigenetic changes associated with endothelial dysfunction in T2DM, in order to identify potential targets that might contribute to pursuing “precision medicine” in the context of diabetic illness.

Influence of socio-demographic characteristics on management of type 2 diabetes mellitus among T2DM clients in Nyandarua South Sub-County, Kenya

2021 ◽  
Vol 2 (1) ◽  
pp. 066-071
Author(s):  
Francis Matheka Muoki ◽  
Ephantus W Kabiru ◽  
Anthony K Wanyoro
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Management Practices ◽  
Complex Disease ◽  
Demographic Characteristics ◽  
University Education ◽  
Cross Sectional ◽  
Management Interventions

Background: Diabetes mellitus (DM) is a complex disease with most complications leading to morbidity and mortality amongst population subsets if not managed. In every six seconds, a person dies from DM or DM related complications. Type 2 diabetes mellitus (T2DM) has markedly increased necessitating active development and implementation of efficient management programs addressing sociodemographic characteristics of diabetic clients. The aim of this study was to determine the influence of socio-demographic characteristics on management of T2DM among type 2 diabetic clients in Nyandarua South sub-County, Kenya. Methods: A cross-sectional facility based study design was used. The study population comprised T2DM clients, aged above 18 years. Systematic random sampling technique was used to select the sample of 294 clients who consented to participate in the study. Data was collected by use of a semi-structured researcher administered questionnaire. Data was analysed using SPSS Version 21. Descriptive statistics were computed to generate frequencies, mean, median and standard deviation. Relationship between socio-demographic factors and management of T2DM was examined using chi-square and bivariate analyses. Results: Majority of the participants were females (59.5%). Slightly more than a quarter of the participants (28%) had good knowledge on management of T2DM. College/university education level was found to be significantly associated with participants’ management of T2DM (OR 5.3666 (1.47-19.58), 95% CI, 1.47-19.58, P=0.0109). Conclusions: Level of education significantly influenced participants’ management of T2DM. The study recommends creation of awareness on T2DM management in Nyandarua County so as to improve clients’ knowledge of management interventions for T2DM health education on T2DM management practices to empower clients to effectively manage the condition.

scholarly journals Endocrine regulation of G-protein subunit production in an animal model of type 2 diabetes mellitus

2001 ◽  
Vol 168 (3) ◽  
pp. 509-515 ◽  
Author(s):  
BD Rodgers ◽  
M Bernier ◽  
MA Levine
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Animal Model ◽  
Type 2 Diabetes Mellitus ◽  
Animal Models ◽  
G Protein ◽  
Dependent Manner ◽  
Protein Subunit

Adipocyte beta-adrenergic sensitivity is compromised in animal models of obesity and type 2 diabetes. Although changes in the membrane concentrations of G-protein alpha subunits (Galpha) have been implicated, it remains to be determined how these changes are affected by insulin resistance in the different animal models. Because previous studies used young animals, we measured the concentrations of Galpha and Gbeta subunits in epididymal fat from aged (48 weeks old) db/db mice and from their lean littermates to more closely reproduce the model of type 2 diabetes mellitus. Levels of immunoreactive Galphas, Galphai(1/2), Galphao and Galphaq/11 were all significantly greater in adipocyte membranes from the db/db mice than in membranes from their lean non-diabetic littermate controls. Levels of Galphai(1) and Galphai(2) were also individually determined and although they appeared to be slightly higher in db/db membranes, these differences were not significant. Although the levels of both Galphas isoforms were elevated, levels of the 42 and 46 kDa proteins rose by approximately 42% and 20% respectively, indicating differential protein processing of Galphas. By contrast, levels of Galphai3 were similar in the two groups. The levels of common Gbeta and Gbeta2 were also elevated in db/db mice, whereas Gbeta1 and Gbeta4 levels were not different. To determine whether these changes were due to insulin resistance per se or to elevated glucocorticoid production, G-protein subunit levels were quantified in whole cell lysates from 3T3-L1 adipocytes that were stimulated with different concentrations of either insulin or corticosterone. Although none of the subunit levels was affected by insulin, the levels of both Galphas isoforms were increased equally by corticosterone in a concentration-dependent manner. Since glucocorticoids are known regulators of Galphas gene expression in many cell types and in adipocytes from diabetic rodents, the results presented herein appear to more accurately reflect diabetic pathophysiology than do those of previous studies which report a decrease in Galphas levels. Taken together, these results indicate that most of the selective changes in G-protein subunit production in adipocytes from this animal model of type 2 diabetes may not be due to diminished insulin sensitivity, but may be due to other endocrine or metabolic abnormalities associated with the diabetic phenotype.

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