666: Maternal bisphenol a (BPA) exposure programs male offspring hepatic insulin signaling protein expression

2015 ◽  
Vol 212 (1) ◽  
pp. S327-S328
Author(s):  
Kristina Galyon ◽  
Farnoosh Farshidi ◽  
Michael Ross ◽  
Mina Desai ◽  
Juanita Jellyman
Keyword(s):  
Bisphenol A ◽  
Protein Expression ◽  
Insulin Signaling ◽  
Male Offspring ◽  
Signaling Protein ◽  
Hepatic Insulin Signaling

scholarly journals Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance

2017 ◽  
Vol 216 (3) ◽  
pp. 290.e1-290.e9 ◽  
Author(s):  
Kristina D. Galyon ◽  
Farnoosh Farshidi ◽  
Guang Han ◽  
Michael G. Ross ◽  
Mina Desai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bisphenol A ◽  
Insulin Signaling ◽  
Protein Abundance ◽  
Signaling Protein ◽  
Rat Offspring

scholarly journals Decreased Capacity for Sperm Production Induced by Perinatal Bisphenol A Exposure Is Associated with an Increased Inflammatory Response in the Offspring of C57BL/6 Male Mice

2018 ◽  
Vol 15 (10) ◽  
pp. 2158 ◽  
Author(s):  
Yuan Meng ◽  
Ren Lin ◽  
Fengjuan Wu ◽  
Qi Sun ◽  
Lihong Jia
Keyword(s):  
Drinking Water ◽  
Inflammatory Response ◽  
Bisphenol A ◽  
Protein Expression ◽  
Sperm Count ◽  
Reproductive Toxicity ◽  
Male Offspring ◽  
Perinatal Exposure ◽  
Sperm Production ◽  
Tnf Α

Many previous studies have indicated the adverse effects of bisphenol A (BPA) on sperm production and quality; however, the mechanisms underlying BPA male reproductive toxicity have yet to be elucidated. The main purpose of this study was to investigate the effect of perinatal exposure to BPA on the spermatogenic capacity of male offspring, and to explore the possible influence of inflammatory responses in BPA reproductive toxicity. Twenty-one pregnant C57BL/6mice were randomly divided into three groups: a control group, a group receiving 0.2 μg/mL (LBPA), and a group receiving 2 μg/mL of BPA (HBPA), all via drinking water from gestational day 6 to the end of lactation. After weaning, one male mouse was randomly selected from each group (n = 7/group); these three mice were fed a normal diet and drinking water for 1 month. Levels of serum testosterone (T) and tumor necrosis factor (TNF)-α were then measured in all mice. Sperm count and the proportion of sperm malformation were also determined. The levels of Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, and aryl hydrocarbon receptor (AhR) protein expression in the testis tissue were determined. Analysis showed that the proportion of sperm malformation increased in the LBPA and HBPA groups (p < 0.05). Sperm count significantly decreased only in the HBPA group (p < 0.05), while the levels of serum TNF-α increased in the LBPA and HBPA groups (p < 0.05). Levels of serum T decreased significantly in the HBPA group, compared with controls (p < 0.05). Levels of TLR4 and NF-κB protein expression in the testis were significantly higher in the LBPA and HBPA groups (p < 0.05 or p < 0.01), while AhR protein expression was higher and seminiferous tubules in the testis showed more damage in the HBPA group compared to controls (p < 0.05 and p < 0.01, respectively). Our results showed that perinatal exposure to low or high doses of BPA decreased the capacity for spermatogenesis in male offspring, which may be associated with an inflammatory response activated by the TLR4/ NF-κB and AhR signaling pathways in the testis.

scholarly journals Dynamic Functional Relay between Insulin Receptor Substrate 1 and 2 in Hepatic Insulin Signaling during Fasting and Feeding

2008 ◽  
Vol 8 (1) ◽  
pp. 49-64 ◽  
Author(s):  
Naoto Kubota ◽  
Tetsuya Kubota ◽  
Shinsuke Itoh ◽  
Hiroki Kumagai ◽  
Hideki Kozono ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Insulin Signaling ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1 ◽  
Hepatic Insulin Signaling

Comparison of protein expression in plasma from nonylphenol and bisphenol A-exposed Atlantic cod (Gadus morhua) and turbot (Scophthalmus maximus) by use of SELDI-TOF

2006 ◽  
Vol 78 ◽  
pp. S25-S33 ◽  
Author(s):  
Bodil K. Larsen ◽  
Anne Bjørnstad ◽  
Rolf C. Sundt ◽  
Ingrid C. Taban ◽  
Daniela M. Pampanin ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Protein Expression ◽  
Gadus Morhua ◽  
Atlantic Cod ◽  
Scophthalmus Maximus ◽  
Turbot Scophthalmus Maximus

P4-051: Effect of Analog P165 of APP 5-mer Peptide on Insulin Signaling Protein in Type 3 Diabetes Rats

2010 ◽  
Vol 6 ◽  
pp. e35-e35
Author(s):  
Rong Wang ◽  
Xiang Hong Meng ◽  
Zhi Wei Zhao ◽  
Zhi Juan Ji ◽  
Shu Li Sheng
Keyword(s):  
Insulin Signaling ◽  
Signaling Protein ◽  
Type 3 Diabetes ◽  
Type 3

scholarly journals EET Analog Treatment Improves Insulin Signaling in a Genetic Mouse Model of Insulin Resistance

2021 ◽  
Author(s):  
Kakali Ghoshal ◽  
Xiyue Li ◽  
Dungeng Peng ◽  
John R. Falck ◽  
Raghunath Reddy Anugu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Signaling ◽  
Genetic Model ◽  
Water Soluble ◽  
Hepatic Insulin Resistance ◽  
Epoxyeicosatrienoic Acid ◽  
Genetic Mouse Model ◽  
Hepatic Insulin Signaling ◽  
Underlying Mechanisms

We previously showed that global deletion of the cytochrome P450 epoxygenase <i>Cyp2c44</i>, a major epoxyeicosatrienoic acid (EET) producing enzyme in mice, leads to impaired hepatic insulin signaling resulting in insulin resistance. This finding led us to investigate whether administration of a water soluble EET analog restores insulin signaling <i>in vivo</i> in <i>Cyp2c44(-/-)</i> mice and investigated the underlying mechanisms by which this effect is exerted. <i>Cyp2c44(-/-)</i> mice treated with the analog EET-A for 4 weeks improved fasting glucose and glucose tolerance compared to <i>Cyp2c44(-/-)</i> mice treated with vehicle alone. This beneficial effect was accompanied by enhanced hepatic insulin signaling, decreased expression of gluconeogenic genes and increased expression of glycogenic genes. Mechanistically, we show that insulin-stimulated phosphorylation of insulin receptor β (IRβ) is impaired in primary <i>Cyp2c44(-/-) </i>hepatocytes and this can be restored by cotreatment with EET-A and insulin. Plasma membrane fractionations of livers indicated that EET-A enhances the retention of IRβ in membrane rich fractions, thus potentiating its activation. Altogether, EET analogs ameliorate insulin signaling in a genetic model of hepatic insulin resistance by stabilizing membrane-associated IRβ and potentiating insulin signaling.

Abstract 628: Hepatic Insulin Signaling Regulates ApoA-I Gene Expression Through the Type I Deiodinase.

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jing Liu ◽  
Antonio Hernandez-Ono ◽  
Valerie Galton ◽  
Henry Ginsberg
Keyword(s):  
Insulin Signaling ◽  
Knockout Mice ◽  
Hepg2 Cells ◽  
Density Lipoprotein ◽  
Type I ◽  
Mrna Levels ◽  
Reverse T3 ◽  
Hepatic Insulin Signaling ◽  
Low Levels

People with low levels of high density lipoprotein cholesterol (HDLC) and apolipoprotein A-I (ApoA-I) have a higher risk of cardiovascular disease. Low levels of HDLC are common in individuals who are insulin resistant (IR), e.g., with metabolic syndrome and type 2 diabetes mellitus (T2DM). Despite the high prevalence of these two disorders, very little work has been reported regarding the molecular pathways linking insulin signaling or action and the levels of either HDLC or ApoA-1. We reported previously that liver specific insulin receptor (InsR) knockout mice (LIRKO) have markedly reduced plasma HDLC levels that increase after restoration of hepatic Akt signaling. In the present study, we created acute LIRKO mice by injecting an albumin-Cre adenovirus (Ad) into InsR floxed mice and observed marked reductions in HDLC, the expression of ApoA-I, and the expression of the gene coding Type1 iodothyronine deiodinase1, a selenoenzyme expressed highly in the liver that converts thyroxine to 3,5,3’-triiodothyronine (T3) or reverse T3. Deiodinase 1 knockout mice also had significantly reduced hepatic ApoA-I mRNA levels. Overexpression of Dio1 in LIRKO restored HDLC and significantly increased the expression of ApoA-I mRNA. In vitro studies showed that the expression of ApoA-I was significantly reduced after knockdown of either InsR or Dio1 expression in HepG2 cells. Moreover, overexpression of Dio1 restored ApoA-I promoter activity that had been decreased by knockdown of InsR. Deletion analysis of ApoAI promoter regions showed that insulin signaling regulated ApoA-I expression by acting on a region which does not contain any thyroid response elements. Pulse-chase experiments in HepG2 cells showed that deficiency of insulin signaling resulted in decreased synthesis and secretion of ApoAI. Our results indicates that defective hepatic insulin signaling results in reduced expression of Dio1 which, in turn, leads to reduced expression of ApoA-I and decreased synthesis and secretion of ApoA-I from hepatocytes. We believe our studies have defined a novel pathway from insulin signaling to ApoA-I synthesis that may lead to new approaches for increasing HDL levels in people with defective insulin signaling.

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