scholarly journals Renal depletion of myo-inositol is associated with its increased degradation in animal models of metabolic disease

2015 ◽  
Vol 309 (9) ◽  
pp. F755-F763 ◽  
Author(s):  
H.-H. Chang ◽  
H.-N. Chao ◽  
C. S. Walker ◽  
S.-Y. Choong ◽  
A. Phillips ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disease ◽  
Animal Models ◽  
De Novo ◽  
Insulin Resistant ◽  
Disease States ◽  
Expression Of Genes ◽  
Pathological Mechanism ◽  
Distinct Disease ◽  
Underlying Mechanisms

Renal depletion of myo-inositol (MI) is associated with the pathogenesis of diabetic nephropathy in animal models, but the underlying mechanisms involved are unclear. We hypothesized that MI depletion was due to changes in inositol metabolism and therefore examined the expression of genes regulating de novo biosynthesis, reabsorption, and catabolism of MI. We also extended the analyses from diabetes mellitus to animal models of dietary-induced obesity and hypertension. We found that renal MI depletion was pervasive across these three distinct disease states in the relative order: hypertension (−51%) > diabetes mellitus (−35%) > dietary-induced obesity (−19%). In 4-wk diabetic kidneys and in kidneys derived from insulin-resistant and hypertensive rats, MI depletion was correlated with activity of the MI-degrading enzyme myo-inositol oxygenase (MIOX). By contrast, there was decreased MIOX expression in 8-wk diabetic kidneys. Immunohistochemistry localized the MI-degrading pathway comprising MIOX and the glucuronate-xylulose (GX) pathway to the proximal tubules within the renal cortex. These findings indicate that MI depletion could reflect increased catabolism through MIOX and the GX pathway and implicate a common pathological mechanism contributing to renal oxidative stress in metabolic disease.

scholarly journals Wireless, battery-free optoelectronic systems as subdermal implants for local tissue oximetry

2019 ◽  
Vol 5 (3) ◽  
pp. eaaw0873 ◽  
Author(s):  
Hao Zhang ◽  
Philipp Gutruf ◽  
Kathleen Meacham ◽  
Michael C. Montana ◽  
Xingyue Zhao ◽  
...  
Keyword(s):  
Animal Models ◽  
Tissue Oxygenation ◽  
Human Subjects ◽  
Brain Regions ◽  
Disease States ◽  
Data Output ◽  
Subdermal Implants ◽  
Underlying Mechanisms ◽  
Tissue Oximetry

Monitoring regional tissue oxygenation in animal models and potentially in human subjects can yield insights into the underlying mechanisms of local O2-mediated physiological processes and provide diagnostic and therapeutic guidance for relevant disease states. Existing technologies for tissue oxygenation assessments involve some combination of disadvantages in requirements for physical tethers, anesthetics, and special apparatus, often with confounding effects on the natural behaviors of test subjects. This work introduces an entirely wireless and fully implantable platform incorporating (i) microscale optoelectronics for continuous sensing of local hemoglobin dynamics and (ii) advanced designs in continuous, wireless power delivery and data output for tether-free operation. These features support in vivo, highly localized tissue oximetry at sites of interest, including deep brain regions of mice, on untethered, awake animal models. The results create many opportunities for studying various O2-mediated processes in naturally behaving subjects, with implications in biomedical research and clinical practice.

scholarly journals Antidiabetic Activities of Muntingia Calabura L. Leaves Water Extract in Type 2 Diabetes Mellitus Animal Models

2018 ◽  
Vol 10 (2) ◽  
pp. 165-70 ◽  
Author(s):  
Widhya Aligita ◽  
Elis Susilawati ◽  
Ika Kurnia Sukmawati ◽  
Lusi Holidayanti ◽  
Jejen Riswanti
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Animal Model ◽  
Blood Glucose ◽  
Animal Models ◽  
Water Extract ◽  
Control Group ◽  
Insulin Deficiency ◽  
Insulin Resistant ◽  
Muntingia Calabura

BACKGROUND: Diabetes Mellitus (DM) is a heterogeneous group of disorders characterized by increasing blood glucose levels caused by insufficiency of insulin hormone production and activities. There are significant increases in DM case every year in Indonesia, as a consequent, alternative and better drug is needed to be developed. One of the plants that were often used as traditional medicine for DM in Indonesia was Muntingia carabula L. (kersen) leaf. The aim of this research was to evaluate the antidiabetes activity of M. carabula leaves.METHODS: This study was conducted in vivo by evaluating the antidiabetic activity of M. carabula leaf water extract on two animal models, those are insulin deficiency and insulin resistant model animal. The insulin deficiency animal model was developed by aloxan administration at dose of 50 mg/Kg body weight (bw) intravenously. While the insulin resistance animal model was developed by lipid emulsion administration at dose of 0.42 mL/20 grams bw orally. Both groups were randomly devided into 6 groups, which are negative control group, positive control group, standard drug group (glybenclamide 0.65 mg/Kg bw or  metformin 135 mg/Kg bw), and extract groups at dose of 100, 200 and 400 mg/Kg bw. Parameters which were evaluated are fasting blood glucose (FBG) levels for insulin deficiency models and values of constant of insulin tolerance (KITT) for insulin resistant models.RESULTS: In insulin deficient model group, administration of glibenclamide lower the FBG by 43%, furthermore, the extract of M. calabura at doses of 100, 200 and 400 mg/Kg bw also lower the FBG by 13%, 22% and 29%, subsequently. In insulin resistant models, metformin increased the value of KITT from less than 0.5 to 2.91, and administration of the extract at doses of 400, 200 and 100 mg/Kg bw also increased the KITT value to 2.31, 1.57, 1.13, respectively.CONCLUSION: The conclusion was M. carabula leaves water extract with dose of 400 mg/Kg bw had the antidiabetic activities with mechanisms to lower blood glucose level, regenerate pancreatic β cells, and increase insulin sensitivity.KEYWORDS: diabetes mellitus, kersen leaves, Muntingia calabura L., insulin deficiency, insulin resistance

scholarly journals Tibetan Medicine for Diabetes Mellitus: Overview of Pharmacological Perspectives

2021 ◽  
Vol 12 ◽  
Author(s):  
Li-Shan Yan ◽  
Brian Chi-Yan Cheng ◽  
Shuo-Feng Zhang ◽  
Gan Luo ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Tibetan Medicine ◽  
Lipid Lowering ◽  
Comprehensive Overview ◽  
Materia Medica ◽  
Insulin Resistant ◽  
Beneficial Effects ◽  
Traditional Tibetan Medicine ◽  
Underlying Mechanisms ◽  
Oxidative Effects

Diabetes mellitus (DM) and its complications pose a major public health threat which is approaching epidemic proportions globally. Current drug options may not provide good efficacy and even cause serious adverse effects. Seeking safe and effective agents for DM treatment has been an area of intensive interest. As a healing system originating in Tibet, Traditional Tibetan Medicine (TTM) has been widely used by Tibetan people for the prevention and treatment of DM and its complications for hundreds of years. Tibetan Materia Medica (TMM) including the flower of Edgeworthia gardneri (Wall.) Meisn., Phyllanthi Fructus, Chebulae Fructus, Huidouba, and Berberidis Cortex are most frequently used and studied. These TMMs possess hypoglycemic, anti-insulin resistant, anti-glycation, lipid lowering, anti-inflammatory, and anti-oxidative effects. The underlying mechanisms of these actions may be related to their α-glucosidase inhibitory, insulin signaling promoting, PPARs-activating, gut microbiota modulation, islet β cell-preserving, and TNF-α signaling suppressive properties. This review presents a comprehensive overview of the mode and mechanisms of action of various active constituents, extracts, preparations, and formulas from TMM. The dynamic beneficial effects of the products prepared from TMM for the management of DM and its complications are summarized. These TMMs are valuable materia medica which have the potential to be developed as safe and effective anti-DM agents.

scholarly journals Paternal epigenetic programming: evolving metabolic disease risk

2017 ◽  
Vol 58 (3) ◽  
pp. R159-R168 ◽  
Author(s):  
Suzy S J Hur ◽  
Jennifer E Cropley ◽  
Catherine M Suter
Keyword(s):  
Metabolic Disease ◽  
Animal Models ◽  
Disease Risk ◽  
Metabolic Effects ◽  
Evolutionary Significance ◽  
Metabolic Disease Risk ◽  
Animal Phyla ◽  
Underlying Mechanisms ◽  
Multiple Species ◽  
Paternal Programming

Parental health or exposures can affect the lifetime health outcomes of offspring, independently of inherited genotypes. Such ‘epigenetic’ effects occur over a broad range of environmental stressors, including defects in parental metabolism. Although maternal metabolic effects are well documented, it has only recently been established that that there is also an independent paternal contribution to long-term metabolic health. Both paternal undernutrition and overnutrition can induce metabolic phenotypes in immediate offspring, and in some cases, the induced phenotype can affect multiple generations, implying inheritance of an acquired trait. The male lineage transmission of metabolic disease risk in these cases implicates a heritable factor carried by sperm. Sperm-based transmission provides a tractable system to interrogate heritable epigenetic factors influencing metabolism, and as detailed here, animal models of paternal programming have already provided some significant insights. Here, we review the evidence for paternal programming of metabolism in humans and animal models, and the available evidence on potential underlying mechanisms. Programming by paternal metabolism can be observed in multiple species across animal phyla, suggesting that this phenomenon may have a unique evolutionary significance.

Immunsuppression nach Nierentransplantation

2020 ◽  
Vol 24 (03) ◽  
pp. 103-103
Author(s):  
Volker Aßfalg
Keyword(s):  
Diabetes Mellitus ◽  
De Novo ◽  
Onset Diabetes ◽  
Ciclosporin A ◽  
Unerwünschte Nebenwirkungen ◽  
New Onset

Der Goldstandard der Immunsuppression nach Nierentransplantation gemäß aktuellen KDIGO-Empfehlungen 1 besteht nach wie vor aus einem Calcineurininhibitor (CNI), Mycophenolsäure und Steroiden – der sog. Tripel-Therapie. Der große Durchbruch in der Langzeitüberlebensrate von Nierentransplantaten gelang erst in den 1990er-Jahren mit dem Einsatz von Ciclosporin A. Mit Einführung des ähnlich wirkenden, aber potenteren Tacrolimus 2 wurde dieser CNI in die Empfehlungen der KDIGO als Erstlinienpräparat in der de novo Immunsuppression aufgenommen 1. Vonseiten des Nebenwirkungsprofils zeigen die CNI jedoch unerwünschte Nebenwirkungen wie z. B. Nephrotoxizität, die im Rahmen der sog. CNI-Toxizität die Transplantatlangzeitfunktion einschränken und limitieren kann. Darüber hinaus findet sich ein erhöhtes Risiko für Hypertonie, Fettstoffwechselstörungen und insbesondere für Tacrolimus die Auslösung eines Post-Transplantations-Diabetes (NODAT: New Onset Diabetes After Transplantation) oder Aggravierung eines bestehenden Diabetes mellitus.

Mechanisms underlying heart failure in type 2 diabetes mellitus

2019 ◽  
pp. 37-39
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Experimental Studies ◽  
Vascular Complications ◽  
Molecular Alterations ◽  
Increased Risk ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Cardio Vascular

The prevalence of heart failure is markedly increased in individuals with diabetes mellitus. Numerous observational studies suggest that this increased risk for heart failure can be attributed to exacerbated vascular complications and the presence of increased risk factors in diabetic subjects. In addition, experimental studies revealed the presence of a number of distinct molecular alterations in the myocardium that occur independently of vascular disease and hypertension. Many of these molecular alterations are similarly observed in failing hearts of nondiabetic patients and have thus been proposed to contribute to the increased risk for heart failure in diabetes. The interest in understanding the underlying mechanisms of impaired cardio- vascular outcomes in diabetic individuals has much increased since the demonstration of cardioprotective effects of SGLT-2 inhibitors and GLP-1 receptor agonists in recent clinical trials. The current review therefore summarizes the distinct mechanisms that have been proposed to increase the risk for heart failure in diabetes mellitus.

Insulin Therapy in Pregnancy Hypertensive Diseases and its Effect on the Offspring and Mother Later in Life

2019 ◽  
Vol 17 (5) ◽  
pp. 455-464 ◽  
Author(s):  
Alfonso Mate ◽  
Antonio J. Blanca ◽  
Rocío Salsoso ◽  
Fernando Toledo ◽  
Pablo Stiefel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Insulin Therapy ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Insulin Resistant ◽  
Hypertensive Disorders ◽  
The Impact ◽  
In Pregnancy

Pregnancy hypertensive disorders such as Preeclampsia (PE) are strongly correlated with insulin resistance, a condition in which the metabolic handling of D-glucose is deficient. In addition, the impact of preeclampsia is enhanced by other insulin-resistant disorders, including polycystic ovary syndrome and obesity. For this reason, there is a clear association between maternal insulin resistance, polycystic ovary syndrome, obesity and the development of PE. However, whether PE is a consequence or the cause of these disorders is still unclear. Insulin therapy is usually recommended to pregnant women with diabetes mellitus when dietary and lifestyle measures have failed. The advantage of insulin therapy for Gestational Diabetes Mellitus (GDM) patients with hypertension is still controversial; surprisingly, there are no studies in which insulin therapy has been used in patients with hypertension in pregnancy without or with an established GDM. This review is focused on the use of insulin therapy in hypertensive disorders in the pregnancy and its effect on offspring and mother later in life. PubMed and relevant medical databases have been screened for literature covering research in the field especially in the last 5-10 years.

Mechanisms Involved in Glycemic Control Promoted by Exercise in Diabetics

2019 ◽  
Vol 15 (2) ◽  
pp. 105-110 ◽  
Author(s):  
Eric Francelino Andrade ◽  
Víviam de Oliveira Silva ◽  
Débora Ribeiro Orlando ◽  
Luciano José Pereira
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disease ◽  
Skeletal Muscle ◽  
Glycemic Control ◽  
Sedentary Lifestyle ◽  
World Population ◽  
Pharmacological Interventions ◽  
High Prevalence ◽  
The World ◽  
Main Factors

Introduction: Diabetes mellitus is a metabolic disease characterized by high glycemic levels for long periods. This disease has a high prevalence in the world population, being currently observed an increase in its incidence. This fact is mainly due to the sedentary lifestyle and hypercaloric diets. Non-pharmacological interventions for glycemic control include exercise, which promotes changes in skeletal muscle and adipocytes. Thus, increased glucose uptake by skeletal muscle and decreased insulin resistance through modulating adipocytes are the main factors that improve glycemic control against diabetes. Conclusion: It was sought to elucidate mechanisms involved in the improvement of glycemic control in diabetics in front of the exercise.

Sign in / Sign up

Export Citation Format

Share Document