scholarly journals The role of polycarbonate monomer bisphenol-A in insulin resistance

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3809 ◽  
Author(s):  
Milos Pjanic

Bisphenol A (BPA) is a synthetic unit of polycarbonate polymers and epoxy resins, the types of plastics that could be found in essentially every human population and incorporated into almost every aspect of the modern human society. BPA polymers appear in a wide range of products, from liquid storages (plastic bottles, can and glass linings, water pipes and tanks) and food storages (plastics wraps and containers), to medical and dental devices. BPA polymers could be hydrolyzed spontaneously or in a photo- or temperature-catalyzed process, providing widespread environmental distribution and chronic exposure to the BPA monomer in contemporary human populations. Bisphenol A is also a xenoestrogen, an endocrine-disrupting chemical (EDC) that interferes with the endocrine system mimicking the effects of an estrogen and could potentially keep our endocrine system in a constant perturbation that parallels endocrine disruption arising during pregnancy, such as insulin resistance (IR). Gestational insulin resistance represents a natural biological phenomenon of higher insulin resistance in peripheral tissues of the pregnant females, when nutrients are increasingly being directed to the embryo instead of being stored in peripheral tissues. Gestational diabetes mellitus may appear in healthy non-diabetic females, due to gestational insulin resistance that leads to increased blood sugar levels and hyperinsulinemia (increased insulin production from the pancreatic beta cells). The hypothesis states that unnoticed and constant exposure to this environmental chemical might potentially lead to the formation of chronic low-level endocrine disruptive state that resembles gestational insulin resistance, which might contribute to the development of diabetes. The increasing body of evidence supports the major premises of this hypothesis, as exemplified by the numerous publications examining the association of BPA and insulin resistance, both epidemiological and mechanistic. However, to what extent BPA might contribute to the development of diabetes in the modern societies still remains unknown. In this review, I discuss the chemical properties of BPA and the sources of BPA contamination found in the environment and in human tissues. I provide an overview of mechanisms for the proposed role of bisphenol A in insulin resistance and diabetes, as well as other related diseases, such as cardiovascular diseases. I describe the transmission of BPA effects to the offspring and postulate that gender related differences might originate from differences in liver enzyme levels, such as UDP-glucuronosyltransferase, which is involved in BPA processing and its elimination from the organism. I discuss the molecular mechanisms of BPA action through nuclear and membrane-bound ER receptors, non-monotonic dose response, epigenetic modifications of the DNA and propose that chronic exposure to weak binders, such as BPA, may mimic the effects of strong binders, such as estrogens.

Author(s):  
Peter A. Furley

What are savannas and where are they? ‘Savanna landscapes’ considers these dynamic and diverse biomes—the most widespread form of vegetation in the tropics and sub-tropics. They are areas covered by a nearly continuous grassy layer, interspersed with trees and shrubs of varying densities and heights, but their nature and distribution is affected by the local topography and is closely allied with continental evolution. Marked seasonal variation is characterized by unpredictably long wet or dry spells and there is a wide range of flora and fauna across the major continental savannas. There are numerous theories on the role of savannas in shaping the emergence and spread of human populations.


2019 ◽  
Vol 20 (9) ◽  
pp. 2109 ◽  
Author(s):  
Arulkumar Nagappan ◽  
Jooyeon Shin ◽  
Myeong Ho Jung

Endogenous cannabinoids (ECs) are lipid-signaling molecules that specifically bind to cannabinoid receptor types 1 and 2 (CB1R and CB2R) and are highly expressed in central and many peripheral tissues under pathological conditions. Activation of hepatic CB1R is associated with obesity, insulin resistance, and impaired metabolic function, owing to increased energy intake and storage, impaired glucose and lipid metabolism, and enhanced oxidative stress and inflammatory responses. Additionally, blocking peripheral CB1R improves insulin sensitivity and glucose metabolism and also reduces hepatic steatosis and body weight in obese mice. Thus, targeting EC receptors, especially CB1R, may provide a potential therapeutic strategy against obesity and insulin resistance. There are many CB1R antagonists, including inverse agonists and natural compounds that target CB1R and can reduce body weight, adiposity, and hepatic steatosis, and those that improve insulin sensitivity and reverse leptin resistance. Recently, the use of CB1R antagonists was suspended due to adverse central effects, and this caused a major setback in the development of CB1R antagonists. Recent studies, however, have focused on development of antagonists lacking adverse effects. In this review, we detail the important role of CB1R in hepatic insulin resistance and the possible underlying mechanisms, and the therapeutic potential of CB1R targeting is also discussed.


1982 ◽  
Vol 52 (4) ◽  
pp. 1071-1076 ◽  
Author(s):  
T. W. Wallis ◽  
W. R. Rogers ◽  
W. G. Johanson

Normal baboons, like humans, demonstrate a wide range of bronchial reactivity to inhaled methacholine. Cigarette-smoking baboons demonstrate reduced bronchial reactivity to inhaled methacholine compared with sham-smoking controls after 6 pack-yr of smoking. To evaluate the role of nicotine in this blunting of airway reactivity, we studied the effects of both acute and chronic nicotine inhalation on reactivity to methacholine in baboons. Inhalation of 2 mg of nicotine had no acute effect on lung function but blunted bronchial reactivity in highly reactive animals. This effect was not diminished after daily inhalation of nicotine for 90 days. Marked interindividual differences in bronchial reactivity to methacholine were not abolished by propranolol, suggesting that factors other than beta-adrenergic tone account for this intersubject variability.


2016 ◽  
Vol 10 (1) ◽  
pp. 122-130 ◽  
Author(s):  
Ciro Menale ◽  
Damiano G. Mita ◽  
Nadia Diano ◽  
Sabrina Diano

Bisphenol A (BPA) is used as basic chemical compound in the production of polycarbonate food containers or epoxy resins coating metallic cans for food and beverages conservation. Its xeno-estrogenic activity alters endocrine-metabolic pathways modulating glucose metabolism and increasing the risk of developing diabetes, insulin resistance, and obesity. Based on in vitro and in vivo experimental research, here we report some of the major BPA adverse effects on tissues that play a key role in the regulation on the whole body’s metabolism. Evidences have shown that BPA is able to exert its endocrine disrupting action altering glucose metabolism and contributing to the onset of metabolic disorders, acting on liver functions and affecting insulin production by the pancreas. Exposure to BPA has been reported also to modulate glucose utilization in muscles, as well as to interfere with adipose tissue endocrine function. In addition, to peripheral tissues, recent studies have shown that BPA by acting in the Central Nervous System affects neuroendocrine regulation of glucose metabolism, promoting glucose metabolism dysfunction such as glucose intolerance and insulin resistance. Thus, exposure to BPA seems to be an important risk factor in the onset of obesity and metabolic syndrome. However, its mechanisms of action need to be further investigated to provide a major evaluation of risk assessment.


2020 ◽  
Author(s):  
Min Liu ◽  
Lujing Wang ◽  
Xigan Li ◽  
Yucui Wu ◽  
Fei Yin ◽  
...  

Abstract Background: Trilobatin, a natural compound, has been found to exhibit anti-diabetic properties in high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic mice. But up to now no research has been reported on the effect of trilobatin on insulin resistance in peripheral tissues. Herein, we determined the effects of trilobatin on insulin resistance in palmitate-treated C2C12 myotubes and ob/ob mice.Methods: 8-10 weeks of male ob/ob mice and same background C57BL/6 mice were used to evaluate the role of trilobatin on insulin resistance; Protein expression and phosphorylation were measured by western blot; Glucose uptake was determined a fluorescent test.Results: treatment with trilobatin prevented palmitate-induced insulin resistance by enhancing glucose uptake and the phosphorylation of IRS1 and AKT, recovered the translocation of GLUT4 from cytoplasm to membrane, but preincubation with LY294002, an inhibitor of PI3K, blocked the effects of trilobatin on glucose uptake and the distribution of GLUT4 in C2C12 myotubes. Furthermore, administration with trilobatin for 4 weeks significantly improved insulin resistance by decreasing fasting blood glucose and insulin in serum, enhancing the phosphorylation of IRS1 and AKT, and recovering the expression and translocation of GLUT4 in ob/ob mice.Conclusions: IRS-AKT-GLUT4 signaling pathway might be involved in trilobatin ameliorating insulin resistance in skeletal muscle of obese animal models.


Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 100
Author(s):  
Małgorzata Mirr ◽  
Maciej Owecki

Insulin resistance refers to the diminished response of peripheral tissues to insulin and is considered the major risk factor for type 2 diabetes. Although many possible mechanisms have been reported to develop insulin resistance, the exact underlying processes remain unclear. In recent years, the role of adipose tissue as a highly active metabolic and endocrine organ, producing proteins called adipokines and their multidirectional activities has gained interest. The physiological effects of adipokines include energy homeostasis and insulin sensitivity regulation. In addition, an excess of adipose tissue is followed by proinflammatory state which results in dysregulation of secreted cytokines contributing to insulin resistance. Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP-1), also known as CCN4, has recently been described as a novel adipokine, whose circulating levels are elevated in obese and insulin resistant individuals. Growing evidence suggests that WISP-1 may participate in the impaired glucose homeostasis. In this review, we characterize WISP-1 and summarize the latest reports on the role of WISP-1 in obesity, insulin resistance and type 2 diabetes.


2013 ◽  
Vol 6 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Gerry Stephen Oxford ◽  
Joyce Harts Hurley

TRP channels are members of a large family of non-selective cation channels. The family which numbers over 30 is classified into 6 groups based on amino acid sequence homology. TRP channels are distributed in many peripheral tissues as well as central and peripheral nervous system. These channels are important in sensing a wide range of chemical and physical stimuli. Several TRP channels, including TRPV1 and TRPA1 are important in pain transduction pathways. This review will focus on the function of TRP channels in the trigeminovascular system and other anatomical regions which are relevant to migraine. We will discuss the possible role of TRP channels in migraine, including the potential role of TRPV1 in the hypersensitivity and allodynia frequently observed in migraine patients. We will review the status of TRP channel drugs in migraine therapeutics. We will also discuss the possible roles of TRP channels in triggering migraine attacks, a process which is not well-understood.


Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2224 ◽  
Author(s):  
Alina Kuryłowicz ◽  
Krzysztof Koźniewski

One of the concepts explaining the coincidence of obesity and type 2 diabetes (T2D) is the metaflammation theory. This chronic, low-grade inflammatory state originating from metabolic cells in response to excess nutrients, contributes to the development of T2D by increasing insulin resistance in peripheral tissues (mainly in the liver, muscles, and adipose tissue) and by targeting pancreatic islets and in this way impairing insulin secretion. Given the role of this not related to infection inflammation in the development of both: insulin resistance and insulitis, anti-inflammatory strategies could be helpful not only to control T2D symptoms but also to treat its causes. This review presents current concepts regarding the role of metaflammation in the development of T2D in obese individuals as well as data concerning possible application of different anti-inflammatory strategies (including lifestyle interventions, the extra-glycemic potential of classical antidiabetic compounds, nonsteroidal anti-inflammatory drugs, immunomodulatory therapies, and bariatric surgery) in the management of T2D.


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