scholarly journals Role of Environmental Chemicals in Diabetes and Obesity: A National Toxicology Program Workshop Review

2012 ◽  
Vol 120 (6) ◽  
pp. 779-789 ◽  
Author(s):  
Kristina A. Thayer ◽  
Jerrold J. Heindel ◽  
John R. Bucher ◽  
Michael A. Gallo
Keyword(s):  
Environmental Chemicals ◽  
National Toxicology Program ◽  
Diabetes And Obesity

scholarly journals The Role of Non-Chemical Stressors in Mediating Socioeconomic Susceptibility to Environmental Chemicals

2014 ◽  
Vol 1 (4) ◽  
pp. 302-313 ◽  
Author(s):  
Jane E. Clougherty ◽  
Jessie L. C. Shmool ◽  
Laura D. Kubzansky
Keyword(s):  
Environmental Chemicals

Carboxylesterase overexpression in the male reproductive tract: a universal safeguarding mechanism?

1999 ◽  
Vol 11 (3) ◽  
pp. 133 ◽  
Author(s):  
A. T. Mikhailov ◽  
M. Torrado
Keyword(s):  
Reproductive Tract ◽  
Expression Patterns ◽  
Cell Lineage ◽  
Environmental Chemicals ◽  
Male Reproductive Tract ◽  
Morphological Organization ◽  
Associated Functions ◽  
And Function ◽  
Hypothetical Explanation

Data on expression patterns of carboxylesterases in the male reproductive tract of different animal groups (i.e. bivalve mollusks, fruitflies and rodents) are summarized to highlight some particularly interesting questions in the context of sperm differentiation, maturation and function. The male reproduc-tive system, in spite of extreme variation in the anatomical/morphological organization in different species, is characterized by similar patterns of male-dependent carboxylesterase overexpression. The phenomenon of conserved carboxylesterase overexpression indicates similar male sex-associated functions of the enzymes. There is possible evidence of carboxylesterase recruitment by male reproductive-tract tissues indi-cating that it could be adaptive for spermatogenesis, sperm maturation and sperm use. Moreover, this idea can be extended to include a sperm cell lineage protection. This issue is discussed in the light of recent data on environmental reproductive xenobiotics that can provide a basis for a hypothetical explanation of car-boxylesterase overexpression in the male reproductive tract. Based on a well-known role of car-boxylesterases in detoxification of environmental chemicals such as organophosphate pesticides, it is proposed that various male genital tract carboxylesterases may be characterized by a similar physiological function to protect the male reproductive system against xenobiotic influences that could provoke its dys-function, thus altering sperm differentiation and maturation.

scholarly journals Gut as an emerging organ for the treatment of diabetes: focus on mechanism of action of bariatric and endoscopic interventions

2018 ◽  
Vol 237 (1) ◽  
pp. R1-R17 ◽  
Author(s):  
Martin Haluzík ◽  
Helena Kratochvílová ◽  
Denisa Haluzíková ◽  
Miloš Mráz
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Therapeutic Option ◽  
Gastrointestinal Hormones ◽  
Less Invasive ◽  
Treatment Of Diabetes ◽  
Endoscopic Methods ◽  
Diabetes And Obesity

Increasing worldwide prevalence of type 2 diabetes mellitus and its accompanying pathologies such as obesity, arterial hypertension and dyslipidemia represents one of the most important challenges of current medicine. Despite intensive efforts, high percentage of patients with type 2 diabetes does not achieve treatment goals and struggle with increasing body weight and poor glucose control. While novel classes of antidiabetic medications such as incretin-based therapies and gliflozins have some favorable characteristics compared to older antidiabetics, the only therapeutic option shown to substantially modify the progression of diabetes or to achieve its remission is bariatric surgery. Its efficacy in the treatment of diabetes is well established, but the exact underlying modes of action are still only partially described. They include restriction of food amount, enhanced passage of chymus into distal part of small intestine with subsequent modification of gastrointestinal hormones and bile acids secretion, neural mechanisms, changes in gut microbiota and many other possible mechanisms underscoring the importance of the gut in the regulation of glucose metabolism. In addition to bariatric surgery, less-invasive endoscopic methods based on the principles of bariatric surgery were introduced and showed promising results. This review highlights the role of the intestine in the regulation of glucose homeostasis focusing on the mechanisms of action of bariatric and especially endoscopic methods of the treatment of diabetes. A better understanding of these mechanisms may lead to less invasive endoscopic treatments of diabetes and obesity that may complement and widen current therapeutic options.

scholarly journals Macrocyclic Peptides as Allosteric Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

2020 ◽  
Author(s):  
Matthijs J. van Haren ◽  
Yurui Zhang ◽  
Ned Buijs ◽  
Vito Thijssen ◽  
Davide Sartini ◽  
...  
Keyword(s):  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Peptide Inhibitors ◽  
Allosteric Inhibitors ◽  
Disease States ◽  
Potent Inhibition ◽  
Macrocyclic Peptides ◽  
Diabetes And Obesity ◽  
Substrate Competition

<p>Nicotinamide <i>N</i>-methyltransferase (NNMT) methylates nicotinamide to form 1-methylnicotinamide using <i>S</i>-adenosyl-l-methionine (SAM) as the methyl donor. The complexity of the role of NNMT in healthy and disease states is slowly being elucidated and provides indication that NNMT may be an interesting therapeutic target for a variety of diseases including cancer, diabetes, and obesity. Most inhibitors of NNMT described to date are structurally related to one or both of its substrates. In search of structurally diverse NNMT inhibitors, an mRNA display screening technique was used to identify macrocyclic peptides which bind to NNMT. Several of the cyclic peptides identified in this manner show potent inhibition of NNMT with IC<sub>50</sub> values as low as 229 nM. Interestingly, substrate competition experiments reveal that these cyclic peptide inhibitors are noncompetitive with either SAM or NA indicating they may be the first allosteric inhibitors reported for NNMT.</p>

scholarly journals THE MAIN EXOGENOUS AND ENDOGENOUS FACTORS THAT CAN AFFECT THE MORPHOFUNCTIONAL CHARACTERISTICS OF THE THYROID GLAND (LITERATURE REVIEW)

2018 ◽  
Vol 22 (4) ◽  
pp. 760-765
Author(s):  
О.І. Tiron
Keyword(s):  
Thyroid Gland ◽  
Thermal Injury ◽  
Environmental Temperature ◽  
Environmental Chemicals ◽  
The Body ◽  
Endogenous Factors ◽  
Temperature Irradiation ◽  
Excessive Consumption ◽  
And Function

Despite the important role of the thyroid gland in regulating the functions of the body, the gland is quite sensitive to the adverse effects of various factors on the body. The purpose of the work is to analyze modern sources of scientific literature devoted to the study of the influence of exo- and endogenous factors on the morpho-functional properties of the thyroid gland. Literary data on the influence on the thyroid gland of various environmental chemicals, insufficient or excessive consumption of iodine and selenium, vitamin D deficiency, exposure to pharmaceuticals, smoking, environmental temperature, irradiation, infections, stress, as well as factors of the internal environment, such as atherosclerosis and pregnancy. There are a small number of modern scientific studies concerning the influence on the structure and function of the thyroid gland consequences of thermal injury of the skin.

scholarly journals Bisphenol A Altersβ-hCG and MIF Release by Human Placenta: AnIn VitroStudy to Understand the Role of Endometrial Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
C. Mannelli ◽  
F. Ietta ◽  
C. Carotenuto ◽  
R. Romagnoli ◽  
A. Z. Szostek ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Conditioned Medium ◽  
Human Placenta ◽  
Environmental Chemicals ◽  
Endometrial Cells ◽  
Direct Exposure ◽  
And Control ◽  
Cell Conditioned Medium

A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for reproductive success. This might be unbalanced by exposure to environmental chemicals, such as bisphenol A (BPA). As fetoplacental contamination with BPA originates from the maternal compartment, this study investigated the role of the endometrium in BPA effects on the placenta. To this end,in vitrodecidualized stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 : 2) was used on chorionic villous explants from human placenta. Parallel cultures of placental explants were directly exposed to 0.5 nM BPA while, control cultures were exposed to the vehicle (EtOH 0.1%). After 24–48 h, culture medium from BPA-treated and control cultures was assayed for concentration of hormone human Chorionic Gonadotropin (β-hCG) and cytokine Macrophage Migration Inhibitory Factor (MIF). The results showed that direct exposure to BPA stimulated the release of both MIF andβ-hCG. These effects were abolished/diminished in placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis revealed that endometrial cells retain BPA, thus reducing the availability of this chemical for the placenta. The data obtained highlight the importance ofin vitromodels including the maternal component in reproducing the effects of environmental chemicals on human fetus/placenta.

Toxicity characterization of environmental chemicals by the US National Toxicology Program: an overview

2003 ◽  
Vol 206 (4-5) ◽  
pp. 437-445 ◽  
Author(s):  
Rajendra S. Chhabra ◽  
John R. Bucher ◽  
Mary Wolfe ◽  
Christopher Portier
Keyword(s):  
Environmental Chemicals ◽  
National Toxicology Program ◽  
The Us
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