scholarly journals The prognostic outcome of ‘type 2 diabetes mellitus and breast cancer’ association pivots on hypoxia-hyperglycemia axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ilhaam Ayaz Durrani ◽  
Attya Bhatti ◽  
Peter John
Keyword(s):  
Breast Cancer ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Critical Role ◽  
Health Concern ◽  
Diabetic Patients ◽  
Prognostic Outcome

AbstractType 2 diabetes mellitus and breast cancer are complex, chronic, heterogeneous, and multi-factorial diseases; with common risk factors including but not limited to diet, obesity, and age. They also share mutually inclusive phenotypic features such as the metabolic deregulations resulting from hyperglycemia, hypoxic conditions and hormonal imbalances. Although, the association between diabetes and cancer has long been speculated; however, the exact molecular nature of this link remains to be fully elucidated. Both the diseases are leading causes of death worldwide and a causal relationship between the two if not addressed, may translate into a major global health concern. Previous studies have hypothesized hyperglycemia, hyperinsulinemia, hormonal imbalances and chronic inflammation, as some of the possible grounds for explaining how diabetes may lead to cancer initiation, yet further research still needs to be done to validate these proposed mechanisms. At the crux of this dilemma, hyperglycemia and hypoxia are two intimately related states involving an intricate level of crosstalk and hypoxia inducible factor 1, at the center of this, plays a key role in mediating an aggressive disease state, particularly in solid tumors such as breast cancer. Subsequently, elucidating the role of HIF1 in establishing the diabetes-breast cancer link on hypoxia-hyperglycemia axis may not only provide an insight into the molecular mechanisms underlying the association but also, illuminate on the prognostic outcome of the therapeutic targeting of HIF1 signaling in diabetic patients with breast cancer or vice versa. Hence, this review highlights the critical role of HIF1 signaling in patients with both T2DM and breast cancer, potentiates its significance as a prognostic marker in comorbid patients, and further discusses the potential prognostic outcome of targeting HIF1, subsequently establishing the pressing need for HIF1 molecular profiling-based patient selection leading to more effective therapeutic strategies emerging from personalized medicine.

Targeting mTOR Signaling in Type 2 Diabetes Mellitus and Diabetes Complications

2022 ◽  
Vol 23 ◽  
Author(s):  
Lin Yang ◽  
Zhixin Zhang ◽  
Doudou Wang ◽  
Yu Jiang ◽  
Ying Liu
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Protein Complexes ◽  
Cell Metabolism ◽  
Critical Role ◽  
Mtor Inhibitors ◽  
Mtor Signaling

Abstract: The mechanistic target of rapamycin (mTOR) is a pivotal regulator of cell metabolism and growth. In the form of two different multi-protein complexes, mTORC1 and mTORC2, mTOR integrates cellular energy, nutrient and hormonal signals to regulate cellular metabolic homeostasis. In type 2 diabetes mellitus (T2DM) aberrant mTOR signaling underlies its pathological conditions and end-organ complications. Substantial evidence suggests that two mTOR-mediated signaling schemes, mTORC1-p70S6 kinase 1 (S6K1) and mTORC2-protein kinase B (AKT), play a critical role in insulin sensitivity and that their dysfunction contributes to development of T2DM. This review summaries our current understanding of the role of mTOR signaling in T2DM and its associated complications, as well as the potential use of mTOR inhibitors in treatment of T2DM.

scholarly journals A Selective Role of Dietary Anthocyanins and Flavan-3-ols in Reducing the Risk of Type 2 Diabetes Mellitus: A Review of Recent Evidence

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 841 ◽  
Author(s):  
Britt Burton-Freeman ◽  
Michał Brzeziński ◽  
Eunyoung Park ◽  
Amandeep Sandhu ◽  
Di Xiao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Risk Reduction ◽  
Critical Role ◽  
Glucose Absorption ◽  
Diabetes Risk ◽  
Fiber Plant

Type 2 diabetes mellitus (T2DM) is the most common form of DM and its prevalence is increasing worldwide. Because it is a progressive disease, prevention, early detection and disease course modification are possible. Diet plays a critical role in reducing T2DM risk. Therapeutic dietary approaches routinely recommend diets high in plant foods (i.e., vegetables, fruits, whole-grains). In addition to essential micronutrients and fiber, plant-based diets contain a wide-variety of polyphenols, specifically flavonoid compounds. Evidence suggests that flavonoids may confer specific benefits for T2DM risk reduction through pathways influencing glucose absorption and insulin sensitivity and/or secretion. The present review assesses the relationship between dietary flavonoids and diabetes risk reduction reviewing current epidemiology and clinical research. Collectively, the research indicates that certain flavonoids, explicitly anthocyanins and flavan-3-ols and foods rich in these compounds, may have an important role in dietary algorithms aimed to address diabetes risk factors and the development of T2DM.

scholarly journals Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2749 ◽  
Author(s):  
Miguel A. Ortega ◽  
Oscar Fraile-Martínez ◽  
Irene Naya ◽  
Natalio García-Honduvilla ◽  
Melchor Álvarez-Mon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Health Concern ◽  
Public Health Concern ◽  
Wide Range

Obesity is a condition of rising prevalence worldwide, with important socioeconomic implications, being considered as a growing public health concern. Frequently, obesity brings other complications in addition to itself—like Type 2 Diabetes Mellitus (T2DM)—sharing origin, risk factors and pathophysiological mechanisms. In this context, some authors have decided to include both conditions as a unique entity known as “diabesity”. In fact, understanding diabesity as a single disease is possible to maximise the benefits from therapies received in these patients. Gut microbiota plays a key role in individual’s health, and their alterations, either in its composition or derived products are related to a wide range of metabolic disorders like T2DM and obesity. The present work aims to collect the different changes reported in gut microbiota in patients with T2DM associated with obesity and their possible role in the onset, development, and establishment of the disease. Moreover, current research lines to modulate gut microbiota and the potential clinical translation derived from the knowledge of this system will also be reviewed, which may provide support for a better clinical management of such a complex condition.

scholarly journals Role of Sphingosine Kinase in Type 2 Diabetes Mellitus

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanfei Qi ◽  
Wei Wang ◽  
Ziyu Song ◽  
Gulibositan Aji ◽  
Xin Tracy Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Critical Role ◽  
Sphingosine Kinase ◽  
Peripheral Insulin Resistance ◽  
Sphingosine 1 Phosphate ◽  
Druggable Targets

Sphingolipids are a class of essential lipids, functioning as both cell membrane constituents and signaling messengers. In the sphingolipid metabolic network, ceramides serve as the central hub that is hydrolyzed to sphingosine, followed by phosphorylation to sphingosine 1-phosphate (S1P) by sphingosine kinase (SphK). SphK is regarded as a “switch” of the sphingolipid rheostat, as it catalyzes the conversion of ceramide/sphingosine to S1P, which often exhibit opposing biological roles in the cell. Besides, SphK is an important signaling enzyme that has been implicated in the regulation of a wide variety of biological functions. In recent years, an increasing body of evidence has suggested a critical role of SphK in type 2 diabetes mellitus (T2D), although a certain level of controversy remains. Herein, we review recent findings related to SphK in the field of T2D research with a focus on peripheral insulin resistance and pancreatic β-cell failure. It is expected that a comprehensive understanding of the role of SphK and the associated sphingolipids in T2D will help to identify druggable targets for future anti-diabetes therapy.

scholarly journals Regulatory MicroRNAs in T2DM and Breast Cancer

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 819
Author(s):  
Ilhaam Ayaz Durrani ◽  
Attya Bhatti ◽  
Peter John
Keyword(s):  
Breast Cancer ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Cellular Processes ◽  
Tumorigenic Potential ◽  
Cancer Types

MicroRNAs orchestrate the tight regulation of numerous cellular processes and the deregulation in their activities has been implicated in many diseases, including diabetes and cancer. There is an increasing amount of epidemiological evidence associating diabetes, particularly type 2 diabetes mellitus, to an elevated risk of various cancer types, including breast cancer. However, little is yet known about the underlying molecular mechanisms and even less about the role miRNAs play in driving the tumorigenic potential of the cell signaling underlying diabetes pathogenesis. This article reviews the role of miRNA in bridging the diabetes–breast cancer association by discussing specific miRNAs that are implicated in diabetes and breast cancer and highlighting the overlap between the disease-specific regulatory miRNA networks to identify a 20-miRNA signature that is common to both diseases. Potential therapeutic targeting of these molecular players may help to alleviate the socioeconomic burden on public health that is imposed by the type 2 diabetes mellitus (T2DM)–breast cancer association.

scholarly journals Exendin-4 as a Versatile Therapeutic Agent for the Amelioration of Diabetic Changes

2021 ◽  
Author(s):  
Hadi Rajabi ◽  
Mahdi Ahmadi ◽  
Somayeh Aslani ◽  
Shirin Saberianpour ◽  
Reza Rahbarghazi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Signaling Pathways ◽  
Diabetic Patients ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Type 2 diabetes mellitus is a chronic metabolic abnormality leading to microvascular and macrovascular complications. Non-insulin Incretin mimic synthetic peptide exendin-4 was introduced as an anti-diabetic drug which helped diabetic patients with triggering insulin secretion; further researches have revealed an effective role of exendin-4 in treatment of type 2 diabetes mellitus related diseases. Exendin-4 is approximately similar to Glucagon-like peptide, thus it can bind to the glucagon-like peptide-1 receptor and activated different signaling pathways that are involved in various bioactivities such as apoptosis, insulin secretion and inactivation of microglial. In this review, we investigated the interesting role of exendin-4 in various kinds of type 2 diabetes mellitus related disorders through the activation of different signaling pathways.

scholarly journals Enhanced Plasma H2S Levels Associated With Fasting Blood Glucose In Type-2 Diabetes Mellitus

2015 ◽  
Vol 6 (6) ◽  
pp. 11-15 ◽  
Author(s):  
Pinaki Saha ◽  
Piyasa Banerjee ◽  
Prasenjit Pal ◽  
Lakshmisona Auddya ◽  
Santanu Sen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels

Introduction: A number of recent literatures suggest a potential role of H2S and H2S modifying agents in the etiology and management of type-2 diabetes mellitus. Objective: The current study was aimed to evaluate the plasma levels of H2S in the patients with type 2 Diabetes mellitus and to find out if there is any relationship of H2S concentrations with the fasting blood glucose levels. Methods: Plasma H2S levels were measured in sixty two recently diagnosed type 2 diabetic patients and compared with similar number of healthy volunteers as controls. Results: The plasma H2S level in the patients ( 81.17 ± 16.40 micromol/l ) is significantly higher (P< 0.001) than the healthy controls (50.69 ± 8.69 micromol/l) and the H2S levels in plasma have significant positive correlation (r= 0.359, P=0.004) with fasting blood glucose levels. Conclusion: The present study has elucidated that the patients with type-2 diabetes mellitus are associated with elevated plasma H2S levels which are well correlated with glucose levels. This reveals a potential the role of H2S modulators towards the management of this non-communicable epidemic disorder. DOI: http://dx.doi.org/10.3126/ajms.v6i6.12532Asian Journal of Medical Sciences Vol.6(6) 2015 11-15

scholarly journals Role of Trace Elements (Serum Zinc & Magnesium) in Type 2 Diabetes Mellitus-A Hospital Based Study

2021 ◽  
pp. 358-364
Author(s):  
J. Saravana Jagan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Serum Magnesium ◽  
Vascular Complications ◽  
Serum Zinc ◽  
Diabetic Patients ◽  
Medical College

This study was undertaken with the aim to determine Serum zinc and magnesium levels in patients with Type 2 Diabetes Mellitus without it's associated complications and Type 2 Diabetes mellitus patients with its various macro and micro vascular complications namely Coronary atherosclerosis, Peripheral vascular disease and retinopathy, nephropathy respectively. The study was conducted at diabetology out-patient department, Sree Balaji Medical college & Hospital, Chennai on total of 120 subjects of age group 40-70 years; of whom 20 were apparently healthy and served as control. Between control groups and retinopathy, a microvascular consequence of Type 2 Diabetes mellitus, there is no statistically significant reduction in serum magnesium. Overall, diabetic patients without comorbidities and microvascular consequences of Type 2 Diabetes mellitus, such as retinopathy and nephropathy, reveal a negative connection between serum magnesium and HbA1c. In diabetes patients without problems and microvascular consequences, such as nephropathy, serum zinc and HbA1c have a negative connection.

scholarly journals Insights into the Molecular Role of Endocannabinoids in Diabetes Mellitus

2021 ◽  
Vol 12 (1) ◽  
pp. 470-485
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cannabinoid Receptors ◽  
The Body ◽  
Diabetic Patients ◽  
Depth Analysis ◽  
Anti Inflammatory

In the past few years, the pathophysiological role of various factors in type 2 diabetes mellitus has been fully explored. Subsequently, this marked the progression in the development of a novel therapeutic agent. Such brain-derived neurotropic factors, including neurotrophic factor-2 and anti-inflammatory agents for the treatment of diabetes, have emerged. However, the therapeutic potential of endocannabinoids in type 2 diabetes mellitus is still not fully understood. At present, cannabinoids are under research for their therapeutic and safety profile issues in numerous thrust areas. Its wide biological actions are implemented through cannabinoid receptor type 1(CB1) and CB2 receptors, which find major applications as anti-arthritic, anti-inflammatory, neuroprotective, anti-cancer, and antidiabetic therapeutics with lesser side effects than any other traditional therapy. The current review aims to reveal detailed aspects of pathological and physiological pathways with endocannabinoids followed in disease progression. Different alterations induced by them in the pancreas, such as 2-arachidonylglycerol and anandamide during hyperglycemia, clearly verify their participation in the progression of type 2 diabetes. Activation of both cannabinoid receptors results in metabolic changes inside the body, and receptor antagonist rimonabant has been proven to be protective in controlling insulin resistance in diabetic patients. Therefore, endocannabinoids are a promising target in new drug developments and further in-depth analysis of their hidden aspects, which would help develop alternate beneficial targets in combating the progression of diabetes.

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