scholarly journals Using Mouse and Drosophila Models to Investigate the Mechanistic Links between Diet, Obesity, Type II Diabetes, and Cancer

2018 ◽  
Vol 19 (12) ◽  
pp. 4110 ◽  
Author(s):  
Coral Warr ◽  
Katherine Shaw ◽  
Arani Azim ◽  
Matthew Piper ◽  
Linda Parsons
Keyword(s):  
Cancer Progression ◽  
Type Ii Diabetes ◽  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Growth Factor Signaling ◽  
Type Ii ◽  
Cancer Models ◽  
Increased Risk ◽  
Diet And Cancer ◽  
Risk Of Cancer

Many of the links between diet and cancer are controversial and over simplified. To date, human epidemiological studies consistently reveal that patients who suffer diet-related obesity and/or type II diabetes have an increased risk of cancer, suffer more aggressive cancers, and respond poorly to current therapies. However, the underlying molecular mechanisms that increase cancer risk and decrease the response to cancer therapies in these patients remain largely unknown. Here, we review studies in mouse cancer models in which either dietary or genetic manipulation has been used to model obesity and/or type II diabetes. These studies demonstrate an emerging role for the conserved insulin and insulin-like growth factor signaling pathways as links between diet and cancer progression. However, these models are time consuming to develop and expensive to maintain. As the world faces an epidemic of obesity and type II diabetes we argue that the development of novel animal models is urgently required. We make the case for Drosophila as providing an unparalleled opportunity to combine dietary manipulation with models of human metabolic disease and cancer. Thus, combining diet and cancer models in Drosophila can rapidly and significantly advance our understanding of the conserved molecular mechanisms that link diet and diet-related metabolic disorders to poor cancer patient prognosis.

scholarly journals Type II transmembrane serine proteases as potential targets for cancer therapy

2016 ◽  
Vol 397 (9) ◽  
pp. 815-826 ◽  
Author(s):  
Andrew S. Murray ◽  
Fausto A. Varela ◽  
Karin List
Keyword(s):  
Cancer Progression ◽  
Serine Proteases ◽  
Molecular Mechanisms ◽  
Inflammatory Cells ◽  
Activity Levels ◽  
Type Ii ◽  
Neoplastic Progression ◽  
Treatment Regimens ◽  
Proinflammatory Mediators ◽  
Transmembrane Serine Protease

Abstract Carcinogenesis is accompanied by increased protein and activity levels of extracellular cell-surface proteases that are capable of modifying the tumor microenvironment by directly cleaving the extracellular matrix, as well as activating growth factors and proinflammatory mediators involved in proliferation and invasion of cancer cells, and recruitment of inflammatory cells. These complex processes ultimately potentiate neoplastic progression leading to local tumor cell invasion, entry into the vasculature, and metastasis to distal sites. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression. In this review the knowledge collected over the past two decades about the molecular mechanisms underlying the pro-cancerous properties of selected TTSPs will be summarized. Furthermore, we will discuss how these insights may facilitate the translation into clinical settings in the future by specifically targeting TTSPs as part of novel cancer treatment regimens.

scholarly journals Cardiac adipose tissue volume and IL-6 level at admission are complementary predictors of severity and short-term mortality in COVID-19 diabetic patients

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Franck Phan ◽  
Samia Boussouar ◽  
Olivier Lucidarme ◽  
Mohamed Zarai ◽  
Joe-Elie Salem ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Intensive Care ◽  
Interleukin 6 ◽  
Type Ii Diabetes ◽  
Troponin T ◽  
Early Mortality ◽  
Diabetic Patients ◽  
Type Ii ◽  
Short Term ◽  
Increased Risk

Abstract Background COVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission. Methods Eighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined. Results Of the enrolled patients (median age 66 years [IQR: 59–74]), 73% male, median body mass index (BMI) 27 kg/m2 [IQR: 24–31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2, p < 0.0001) and ICU-R (respectively OR = 3.27, p = 0.01; OR = 4.86, p = 0.002). These associations remained significant independently of age, sex, BMI as well as troponin-T level and pulmonary lesion extension in CT. We combined CATi and IL-6 levels as a multiplicative interaction score (CATi*IL-6). The cut-point for this score was ≥ 6386 with a sensitivity of 0.90 and a specificity of 0.87 (AUC = 0.88) and an OR of 59.6 for early mortality (p < 0.0001). Conclusions Cardiac adipose tissue index and IL-6 determination at admission could help physicians to better identify diabetic patients with a potentially severe and lethal short term course irrespective of obesity. Diabetic patients with high CATi at admission, a fortiori associated with high IL-6 levels could be a relevant target population to promptly initiate anti-inflammatory therapies.

scholarly journals Fluoride Exposure Induces Inhibition of Sodium-and Potassium-Activated Adenosine Triphosphatase (Na+, K+-ATPase) Enzyme Activity: Molecular Mechanisms and Implications for Public Health

2019 ◽  
Vol 16 (8) ◽  
pp. 1427 ◽  
Author(s):  
Declan Timothy Waugh
Keyword(s):  
Enzyme Activity ◽  
Atpase Activity ◽  
Molecular Mechanisms ◽  
Chemical Elements ◽  
Biological Pathways ◽  
Normal Brain ◽  
Biological Interface ◽  
Increased Risk ◽  
And Function ◽  
Risk Of Cancer

In this study, several lines of evidence are provided to show that Na + , K + -ATPase activity exerts vital roles in normal brain development and function and that loss of enzyme activity is implicated in neurodevelopmental, neuropsychiatric and neurodegenerative disorders, as well as increased risk of cancer, metabolic, pulmonary and cardiovascular disease. Evidence is presented to show that fluoride (F) inhibits Na + , K + -ATPase activity by altering biological pathways through modifying the expression of genes and the activity of glycolytic enzymes, metalloenzymes, hormones, proteins, neuropeptides and cytokines, as well as biological interface interactions that rely on the bioavailability of chemical elements magnesium and manganese to modulate ATP and Na + , K + -ATPase enzyme activity. Taken together, the findings of this study provide unprecedented insights into the molecular mechanisms and biological pathways by which F inhibits Na + , K + -ATPase activity and contributes to the etiology and pathophysiology of diseases associated with impairment of this essential enzyme. Moreover, the findings of this study further suggest that there are windows of susceptibility over the life course where chronic F exposure in pregnancy and early infancy may impair Na + , K + -ATPase activity with both short- and long-term implications for disease and inequalities in health. These findings would warrant considerable attention and potential intervention, not to mention additional research on the potential effects of F intake in contributing to chronic disease.

scholarly journals Longitudinal Associations Between Gait, Falls, and Disability in Community-Dwelling Older Adults With Type II Diabetes Mellitus: Findings From The Irish Longitudinal Study on Ageing (TILDA)

2020 ◽  
Author(s):  
Orna A Donoghue ◽  
Siobhan Leahy ◽  
Rose Anne Kenny
Keyword(s):  
Older Adults ◽  
Dual Task ◽  
Type Ii Diabetes ◽  
Step Length ◽  
Community Dwelling ◽  
Type Ii ◽  
Diabetes Status ◽  
Increased Risk ◽  
Community Dwelling Older Adults ◽  
Task Step

Abstract Background Diabetes is associated with gait deficits, future falls, and disability; however, it is unclear if associations remain after controlling for relevant confounders. This study investigated (i) the effects of type II diabetes on spatiotemporal gait parameters in community-dwelling older adults and (ii) if diabetes status was independently associated with future falls and disability, after controlling for gait and other confounders. Method Baseline data were obtained from 2608 community-dwelling adults (≥60 years) participating in The Irish Longitudinal Study on Ageing (TILDA). Diabetes was identified from self-reported doctors’ diagnosis, medications, and glycated hemoglobin levels. Gait characteristics were obtained during single- and dual-task walking using a GAITRite mat (n = 2560). Incident falls and disability were collected over 4 years follow-up (n = 2473). Associations between diabetes status and gait (cross-sectional) and falls and disability (longitudinal) were investigated using regression analysis, adjusting for medications, cardiovascular health, neuropsychological function, and fall-related factors. Results Diabetes (prevalence = 9.1%) was cross-sectionally associated with shorter dual-task step length after adjusting for covariates (β = −1.59, 95% CI: −3.10, −0.08, p &lt; .05). Diabetes was independently associated with increased risk of future instrumental activity of daily living (IADL) difficulty in those with no prior difficulty (incidence rate ratio [IRR] = 1.51, 95% CI: 1.08, 2.11, p &lt; .05) although dual-task step length was an important confounder in all disability models. No independent associations between diabetes and falls were observed. Conclusions Diabetes was independently associated with shorter dual-task step length and increased risk of future IADL difficulty. Multidimensional interventions addressing poor health and function in those with diabetes may help reduce the risk of gait deficits and future disability.

scholarly journals Cancer Biology and Prevention in Diabetes

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1380 ◽  
Author(s):  
Swayam Prakash Srivastava ◽  
Julie E. Goodwin
Keyword(s):  
Type Ii Diabetes ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Type I Diabetes ◽  
Type I ◽  
Type Ii ◽  
Mesenchymal Transition ◽  
Wide Range ◽  
Risk Of Cancer

The available evidence suggests a complex relationship between diabetes and cancer. Epidemiological data suggest a positive correlation, however, in certain types of cancer, a more complex picture emerges, such as in some site-specific cancers being specific to type I diabetes but not to type II diabetes. Reports share common and differential mechanisms which affect the relationship between diabetes and cancer. We discuss the use of antidiabetic drugs in a wide range of cancer therapy and cancer therapeutics in the development of hyperglycemia, especially antineoplastic drugs which often induce hyperglycemia by targeting insulin/IGF-1 signaling. Similarly, dipeptidyl peptidase 4 (DPP-4), a well-known target in type II diabetes mellitus, has differential effects on cancer types. Past studies suggest a protective role of DPP-4 inhibitors, but recent studies show that DPP-4 inhibition induces cancer metastasis. Moreover, molecular pathological mechanisms of cancer in diabetes are currently largely unclear. The cancer-causing mechanisms in diabetes have been shown to be complex, including excessive ROS-formation, destruction of essential biomolecules, chronic inflammation, and impaired healing phenomena, collectively leading to carcinogenesis in diabetic conditions. Diabetes-associated epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndMT) contribute to cancer-associated fibroblast (CAF) formation in tumors, allowing the epithelium and endothelium to enable tumor cell extravasation. In this review, we discuss the risk of cancer associated with anti-diabetic therapies, including DPP-4 inhibitors and SGLT2 inhibitors, and the role of catechol-o-methyltransferase (COMT), AMPK, and cell-specific glucocorticoid receptors in cancer biology. We explore possible mechanistic links between diabetes and cancer biology and discuss new therapeutic approaches.

scholarly journals Future of environmental research in the age of epigenomics and exposomics

2017 ◽  
Vol 32 (1-2) ◽  
pp. 45-54 ◽  
Author(s):  
Nina Holland
Keyword(s):  
Public Health ◽  
Molecular Mechanisms ◽  
Environmental Research ◽  
Whole Body ◽  
Epigenetic Mechanisms ◽  
Multifactorial Diseases ◽  
Adverse Health Outcomes ◽  
Increased Risk ◽  
Susceptible Populations ◽  
Risk Of Cancer

Abstract Environmental research and public health in the 21st century face serious challenges such as increased air pollution and global warming, widespread use of potentially harmful chemicals including pesticides, plasticizers, and other endocrine disruptors, and radical changes in nutrition and lifestyle typical of modern societies. In particular, exposure to environmental and occupational toxicants may contribute to the occurrence of adverse birth outcomes, neurodevelopmental deficits, and increased risk of cancer and other multifactorial diseases such as diabetes and asthma. Rapidly evolving methodologies of exposure assessment and the conceptual framework of the Exposome, first introduced in 2005, are new frontiers of environmental research. Metabolomics and adductomics provide remarkable opportunities for a better understanding of exposure and prediction of potential adverse health outcomes. Metabolomics, the study of metabolism at whole-body level, involves assessment of the total repertoire of small molecules present in a biological sample, shedding light on interactions between gene expression, protein expression, and the environment. Advances in genomics, transcriptomics, and epigenomics are generating multidimensional structures of biomarkers of effect and susceptibility, increasingly important for the understanding of molecular mechanisms and the emergence of personalized medicine. Epigenetic mechanisms, particularly DNA methylation and miRNA expression, attract increasing attention as potential links between the genetic and environmental determinants of health and disease. Unlike genetics, epigenetic mechanisms could be reversible and an understanding of their role may lead to better protection of susceptible populations and improved public health.

PERILOUS HIV BRINGS OUT DEADLY CANCERS

2020 ◽  
pp. 1-5
Author(s):  
Camila A Carlman ◽  
Bharat Mishra ◽  
Anita Patel
Keyword(s):  
Immune System ◽  
Hodgkin Lymphoma ◽  
Cancer Progression ◽  
Kaposi's Sarcoma ◽  
Cellular Proliferation ◽  
Kaposi’S Sarcoma ◽  
Hiv Patients ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk ◽  
Risk Of Cancer

Human Immunodeficiency Virus (HIV) infection is both infectious and contagious disease. The people infected with HIV have an increased risk of cancer while comparing with uninfected people. Kaposi’s sarcoma, aggressive B-cell Non-Hodgkin Lymphoma & cervical cancer are the three types of cancers which are termed as “HIV –associated cancers”. Apart from these cancers, HIV patients are prone to cancers of anus, liver, lung, pharynx which are termed as “non-AIDS defining cancers”. Viral oncogenesis and cytokine induced growth contribute to the development of Kaposi sarcoma. Several virally encoded genes such as bcl-2, IL-6, cyclin-D, GPCR & interferon regulatory factor, plays key role in cellular proliferation and survival.  Infection with HIV weakens the immune system and reduces the body’s ability to fight against viral infections that may lead to cancer. Immunosuppression and inflammation in HIV patients also contribute to cancer progression. The complications of AIDS- related cancers include easy bleeding and bruising, tiredness, nausea, vomiting, poor appetite, mouth sores, hair loss etc. According to the data, HIV infected males are more susceptible to Kaposi’s sarcoma and Non- Hodgkin Lymphoma whereas females are more liable to cervical cancers. Early diagnosis and treatment options help to drop the risk of AIDS related cancers. The HAART therapy reduces the risk of cancer in HIV patients by lowering the amount of HIV circulating in blood, so that function of immune system to fight against the virus can be restored. Other treatment methods are chemotherapy, immunotherapy, radiation and surgery.

Study of Association between Microalbuminuria and Microvascular Complications in Type II Diabetes Mellitus Patients in RajaRajeswari Medical College and Hospital, Karnataka

2017 ◽  
Vol 3 (1) ◽  
pp. 6-10
Author(s):  
N Bhavya ◽  
V Ajith Kumar
Keyword(s):  
Diabetes Mellitus ◽  
Observational Study ◽  
Type Ii Diabetes ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii ◽  
Duration Of Diabetes ◽  
Medical College ◽  
Increased Risk

ABSTRACT Introduction India is claimed to be the diabetes capital of the world. Many studies had proven that persistent hyperglycemia and associated metabolic syndrome features like hypertension, dyslipidemia, and obesity contribute to the development of vascular complications. The risk of chronic complications increases as a function of the duration of hyperglycemia; they usually become apparent in the second decade of hyperglycemia. Since type II diabetes mellitus (DM) often has a long asymptomatic period of hyperglycemia, many individuals with type II DM have complications at the time of diagnosis. The vascular complications of DM are subdivided into microvascular (retinopathy, neuropathy, nephropathy) and macrovascular (coronary artery disease, peripheral arterial disease, cerebro-vascular disease) complications. The present study aims to study the occurrence of microalbuminuria in patients with type II DM and note its association with the duration of diabetes since diagnosis and microvascular complications of DM. Study design Prospective observational study. Materials and methods The study is a clinical, prospective, and observational study of 100 type II diabetics attending the medicine department outpatient/inpatient of RajaRajeswari Medical College & Hospital, Bengaluru, Karnataka, India, who form the subjects for the study conducted from August 2015 to July 2016 (12 months) and who matched the inclusion criteria. Data were collected after obtaining informed/written consent from patient. After detailed history, detailed clinical examination, and general physical and systemic examinations, fundoscopy was carried out and relevant laboratory investigations were done. Results and conclusion The overall occurrence of microalbuminuria was 38%. The occurrence of microalbuminuria showed a direct relationship with increasing age (p = 0.053) and increasing duration of diabetes since diagnosis. A hemoglobin (Hb)A1c value above 7% is associated with 50% or higher incidence of microalbuminuria (p = 0.018). Patients with a body mass index of more than 25kg/m2 have increased risk of developing type II DM and significant increase in microalbuminuria. The incidence of microalbuminuria is significantly associated with How to cite this article Bhavya N, Kumar VA. A Study of Association between Microalbuminuria and Microvascular Complications in Type II Diabetes Mellitus Patients in RajaRajeswari Medical College and Hospital, Karnataka. J Med Sci 2017;3(1):6-10.

scholarly journals Updating Experimental Models of Diabetic Cardiomyopathy

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
J. Fuentes-Antrás ◽  
B. Picatoste ◽  
A. Gómez-Hernández ◽  
J. Egido ◽  
J. Tuñón ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Type Ii Diabetes ◽  
Genetic Manipulation ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Type I ◽  
Type Ii ◽  
Genetic Modifications ◽  
Human Diabetes ◽  
Contractility Of The Myocardium

Diabetic cardiomyopathy entails a serious cardiac dysfunction induced by alterations in structure and contractility of the myocardium. This pathology is initiated by changes in energy substrates and occurs in the absence of atherothrombosis, hypertension, or other cardiomyopathies. Inflammation, hypertrophy, fibrosis, steatosis, and apoptosis in the myocardium have been studied in numerous diabetic experimental models in animals, mostly rodents. Type I and type II diabetes were induced by genetic manipulation, pancreatic toxins, and fat and sweet diets, and animals recapitulate the main features of human diabetes and related cardiomyopathy. In this review we update and discuss the main experimental models of diabetic cardiomyopathy, analysing the associated metabolic, structural, and functional abnormalities, and including current tools for detection of these responses. Also, novel experimental models based on genetic modifications of specific related genes have been discussed. The study of specific pathways or factors responsible for cardiac failures may be useful to design new pharmacological strategies for diabetic patients.

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