scholarly journals Gender difference in the glucagon response to glucopenic stress in mice

2002 ◽  
Vol 282 (1) ◽  
pp. R281-R288 ◽  
Author(s):  
Sven Karlsson ◽  
Anton J. W. Scheurink ◽  
Bo Ahrén
Keyword(s):  
Gender Difference ◽  
Cell Mass ◽  
Plasma Catecholamine ◽  
Plasma Glucagon ◽  
Male Mice ◽  
Female Mice ◽  
Autonomic Activation ◽  
Catecholamine Response ◽  
Increased Sensitivity

A gender difference in the glucagon response to insulin-induced hypoglycemia was previously demonstrated in humans. Whether this reflects a gender difference in autonomic activation or in pancreatic α-cell regulation is not known. We investigated the glucagon, epinephrine, and norepinephrine responses to neuroglycopenic stress induced by 2-deoxy-d-glucose (2-DG) or insulin in female and male mice. 2-DG increased plasma glucagon levels by 559 ± 68% in females versus 281 ± 46% in males ( P< 0.01). Plasma levels of epinephrine or norepinephrine after 2-DG administration did not differ between genders. During insulin-induced hypoglycemia, the glucagon response was similarly higher in females ( P < 0.001), whereas the plasma catecholamine response was higher in males ( P < 0.05). In vivo, the glucagon response to carbachol or clonidine was higher in females ( P < 0.05). In isolated islets, the glucagon response to carbachol (100 μM; P = 0.003) but not to clonidine (1 μM) was larger in females. We conclude that in addition to a larger α-cell mass (previously described in female mice), an increased sensitivity of the glucagon-producing α-cell to cholinergic activation contributes to the larger glucagon response to glucopenic stress in female mice.

scholarly journals An Exaggerated Immune Response in Female BALB/c Mice Controls Initial Toxoplasma gondii Multiplication but Increases Mortality and Morbidity Relative to Male Mice

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1154
Author(s):  
Rasha Alonaizan ◽  
Stuart Woods ◽  
Kerrie E Hargrave ◽  
Craig W. Roberts
Keyword(s):  
Immune Response ◽  
Imaging System ◽  
Acute Infection ◽  
Mortality Rates ◽  
Dependent Manner ◽  
Male Mice ◽  
Female Mice ◽  
Parasite Multiplication ◽  
Parasite Replication

Studies indicate that female mice are more susceptible to T. gondii infection, as defined by higher mortality rates in comparison to male mice. However, whether this is due to an inability to control initial parasite multiplication or due to detrimental effects of the immune system has not been determined. Therefore, the following studies were undertaken to determine the influence of sex on early parasite multiplication and the immune response during T. gondii infection and to correlate this with disease outcome. Early parasite replication was studied through applying an in vivo imaging system (IVIS) with luciferase expressing T. gondii. In parallel immunological events were studied by cytometric bead array to quantify key immunological mediators. The results confirmed the previous findings that female mice are more susceptible to acute infection, as determined by higher mortality rates and weight loss compared with males. However, conflicting with expectations, female mice had lower parasite burdens during the acute infection than male mice. Female mice also exhibited significantly increased production of Monocyte Chemoattractant Protein-1 (MCP-1), Interferon (IFN)-γ, and Tumour Necrosis Factor (TNF)-α than male mice. MCP-1 was found to be induced by T. gondii in a dose dependent manner suggesting that the observed increased levels detected in female mice was due to a host-mediated sex difference rather than due to parasite load. However, MCP-1 was not affected by physiological concentration of estrogen or testosterone, indicating that MCP-1 differences observed between the sexes in vivo are due to an as yet unidentified intermediary factor that in turn influences MCP-1 levels. These results suggest that a stronger immune response in female mice compared with male mice enhances their ability to control parasite replication but increases their morbidity and mortality.

scholarly journals Cytochrome P450 Genes Are Differentially Expressed in Female and Male Hepatocyte Retinoid X Receptor α-Deficient Mice

Endocrinology ◽  
2003 ◽  
Vol 144 (6) ◽  
pp. 2311-2318 ◽  
Author(s):  
Yan Cai ◽  
Tiane Dai ◽  
Yan Ao ◽  
Tamiko Konishi ◽  
Kuang-Hsiang Chuang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Negative Impact ◽  
Retinoid X Receptor ◽  
Differentially Expressed ◽  
Male Mice ◽  
Wild Type ◽  
Male And Female ◽  
Female Mice ◽  
Deficient Mice

Abstract To study the functional role of retinoid X receptor α (RXRα) in hepatocytes, hepatocyte RXRα-deficient mice have been established. Characterization has been performed on male mice. In this paper, we show that the expression of CYP450 genes is differentially expressed in male and female hepatocyte RXRα-deficient mice; male mice have reduced expression of cytochrome P450 (CYP) CYP4A, CYP3A, and CYP2B mRNAs, but females do not exhibit such phenotypes. To examine the hormonal effects on this sexual dimorphic phenotype, male and female mice were subjected to 17β-estradiol and 5α-dihydrotestosterone (DHT) treatment, respectively, and then the expression of the CYP450 genes was studied. Estradiol had no effect on protecting the hepatocyte RXRα-deficient mice from reduced expression of the CYP450 genes. In contrast, DHT induced hepatocyte RXRα-deficient female mice, but not wild-type female mice, to have the reduced expression of CYP450 mRNAs. In addition, castration prevented the mutant male mice from exhibiting reduced expression of CYP450 mRNAs. wild-type and mutant mouse livers from both genders express androgen receptors (ARs). By transient transfection, DHT-AR could inhibit RXRα-mediated transcription. Furthermore, by transfection and coimmunoprecipitation, RXR can interact with AR in vivo. These data suggest that testosterone has a negative impact on retinoid signaling when the level of RXRα is low, which may in turn reduce the expression of the CYP450 genes.

scholarly journals Beta-cell specific insulin resistance promotes glucose-stimulated insulin hypersecretion

2020 ◽  
Author(s):  
Søs Skovsø ◽  
Evgeniy Panzhinskiy ◽  
Jelena Kolic ◽  
Derek A. Dionne ◽  
Xiao-Qing Dai ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Cell Mass ◽  
Whole Body ◽  
Calcium Oscillation ◽  
Male Mice ◽  
Β Cells ◽  
Β Cell ◽  
Specific Insulin

AbstractInsulin receptor (Insr) protein can be found at higher levels in pancreatic β-cells than in most other cell types, but the consequences of β-cell insulin resistance remain enigmatic. Ins1cre allele was used to delete Insr specifically in β-cells of both female and male mice which were compared to Ins1cre-containing littermate controls at multiple ages and on multiple diets. RNA-seq of recombined β-cells revealed significant differences in multiple pathways previously implicated in insulin secretion and cellular fate, including rewired Ras and NFκB signaling. Male, but not female, βInsrKO mice had reduced oxygen consumption rate, while action potential and calcium oscillation frequencies were increased in Insr knockout β-cells from female, but not male mice. Female βInsrKO and βInsrHET mice exhibited elevated insulin release in perifusion experiments, during hyperglycemic clamps, and following i.p. glucose challenge. Deletion of Insr did not reduce β-cell mass up to 9 months of age, nor did it impair hyperglycemia-induced proliferation. Based on our data, we adapted a mathematical model to include β-cell insulin resistance, which predicted that β-cell Insr knockout would improve glucose tolerance depending on the degree of whole-body insulin resistance. Indeed, glucose tolerance was significantly improved in female βInsrKO and βInsrHET mice when compared to controls at 9, 21 and 39 weeks. We did not observe improved glucose tolerance in adult male mice or in high fat diet-fed mice, corroborating the prediction that global insulin resistance obscures the effects of β-cell specific insulin resistance. We further validated our in vivo findings using the Ins1-CreERT transgenic line and found improved glucose tolerance 4 weeks after tamoxifen-mediated Insr deletion. Collectively, our data show that loss of β-cell Insr alone is sufficient to drive glucose-induced hyperinsulinemia, thereby improving glucose homeostasis in otherwise insulin sensitive dietary and age contexts.

scholarly journals Male sex hormones promote vagally mediated reflex airway responsiveness to cholinergic stimulation

2007 ◽  
Vol 292 (4) ◽  
pp. L908-L914 ◽  
Author(s):  
Jeffrey W. Card ◽  
James W. Voltz ◽  
Catherine D. Ferguson ◽  
Michelle A. Carey ◽  
Laura M. DeGraff ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Ex Vivo ◽  
Airway Responsiveness ◽  
Male Mice ◽  
Cholinergic Stimulation ◽  
Intact Female ◽  
Reflex Mechanism ◽  
Female Mice ◽  
Male Sex

A sex disparity in airway responsiveness to cholinergic stimulation has been observed in laboratory mice in that males are considerably more responsive than females, but the basis for this difference is unclear. In this report, we demonstrate that male sex hormones promote murine airway responsiveness to cholinergic stimulation via vagus nerve-mediated reflex mechanisms. In tissue bath preparations, no sex-based differences were observed in the contractile responses of isolated tracheal and bronchial ring segments to carbachol, indicating that the mechanism(s) responsible for the in vivo sex difference is (are) absent ex vivo. Bilateral cervical vagotomy was found to abolish in vivo airway responsiveness to methacholine in male mice, whereas it did not alter the responses of females, suggesting a regulatory role for male sex hormones in promoting reflex airway constriction. To test this possibility, we next studied mice with altered circulating male sex hormone levels. Castrated male mice displayed airway responsiveness equivalent to that observed in intact females, whereas administration of exogenous testosterone to castrated males restored responsiveness, albeit not to the level observed in intact males. Administration of exogenous testosterone to intact female mice similarly enhanced responsiveness. Importantly, the promotive effects of exogenous testosterone in castrated male and intact female mice were absent when bilateral vagotomy was performed. Together, these data indicate that male sex hormones promote cholinergic airway responsiveness via a vagally mediated reflex mechanism that may be important in the regulation of airway tone in the normal and diseased lung.

scholarly journals INFLUENCE OF GENDER DIFFERENCE IN THE ANTIDEPRESSANT EFFECT OF FLUOXETINE IN MICE IN TAIL SUSPENSION TEST

2016 ◽  
Vol 10 (1) ◽  
pp. 230
Author(s):  
Anki Tyagi ◽  
Vaibhav Walia
Keyword(s):  
Gender Difference ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Male Mice ◽  
Tail Suspension ◽  
Swiss Albino Mice ◽  
Female Mice ◽  
Significant Difference ◽  
Immobility Period ◽  
Suspension Test

ABSTRACTAim: To determine the effect of gender difference in the antidepressant effect of fluoxetine (FLX) in mice in tail suspension test (TST).Methods: Swiss albino mice of either sex were used and the depression-like behavior was measured by TST.Results: The present study showed that there was a significant difference in the immobility period of male mice and female mice in TST. However, theantidepressant effect of FLX differs significantly in male mice and female mice in TST.Conclusion: It has been concluded that the antidepressant effect of FLX in TST was affected by the gender difference as suggested by the results ofthe present study.Keywords: Depression, Estrogen, Female, Fluoxetine, Mice, Serotonin.

scholarly journals Long-lived crowded-litter mice exhibit lasting effects on insulin sensitivity and energy homeostasis

2014 ◽  
Vol 306 (11) ◽  
pp. E1305-E1314 ◽  
Author(s):  
Marianna Sadagurski ◽  
Taylor Landeryou ◽  
Manuel Blandino-Rosano ◽  
Gillian Cady ◽  
Lynda Elghazi ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Early Life ◽  
Energy Homeostasis ◽  
Cell Mass ◽  
Adult Life ◽  
Postnatal Growth ◽  
Male Mice ◽  
Β Cell ◽  
Female Mice ◽  
The Impact

The action of nutrients on early postnatal growth can influence mammalian aging and longevity. Recent work has demonstrated that limiting nutrient availability in the first 3 wk of life [by increasing the number of pups in the crowded-litter (CL) model] leads to extension of mean and maximal lifespan in genetically normal mice. In this study, we aimed to characterize the impact of early-life nutrient intervention on glucose metabolism and energy homeostasis in CL mice. In our study, we used mice from litters supplemented to 12 or 15 pups and compared those to control litters limited to eight pups. At weaning and then throughout adult life, CL mice are significantly leaner and consume more oxygen relative to control mice. At 6 mo of age, CL mice had low fasting leptin concentrations, and low-dose leptin injections reduced body weight and food intake more in CL female mice than in controls. At 22 mo, CL female mice also have smaller adipocytes compared with controls. Glucose and insulin tolerance tests show an increase in insulin sensitivity in 6 mo old CL male mice, and females become more insulin sensitive later in life. Furthermore, β-cell mass was significantly reduced in the CL male mice and was associated with reduction in β-cell proliferation rate in these mice. Together, these data show that early-life nutrient intervention has a significant lifelong effect on metabolic characteristics that may contribute to the increased lifespan of CL mice.

Canine adrenal catecholamine response to VIP is blocked by PACAP-(6-27) in vivo

1997 ◽  
Vol 272 (5) ◽  
pp. R1606-R1612 ◽  
Author(s):  
R. Gaspo ◽  
L. Lamarche ◽  
J. de Champlain ◽  
N. Yamaguchi
Keyword(s):  
Muscarinic Receptors ◽  
Control Group ◽  
Plasma Catecholamine ◽  
Type I ◽  
Pituitary Adenylate Cyclase ◽  
Catecholamine Response ◽  
Anesthetized Dogs ◽  
Plasma Catecholamine Concentrations ◽  
Ca2 Channels

The goal of the present study was to characterize the adrenal catecholamine response to exogenous vasoactive intestinal peptide (VIP) in anesthetized dogs. We studied the potential involvement of mechanism(s) mediated by muscarinic receptors, L-type Ca2+ channels, VIP-ergic receptors, or pituitary adenylate cyclase-activating peptide (PACAP) receptors. The study consisted of five groups: a vehicle control group receiving VIP (5 micrograms) in the presence of saline and four drug-treated groups receiving VIP (5 micrograms) in the presence of either atropine (500 micrograms), nifedipine (50 micrograms), [Lys1,Pro2,5,Arg3,4,Tyr6]VIP (50 micrograms), or PACAP-(6-27) (50 micrograms). All drugs were locally infused to the left adrenal gland. Plasma catecholamine concentrations were measured in adrenal venous and aortic blood by a high-pressure liquid chromatography-electrochemical method. In the control group, VIP produced a significant increase in adrenal catecholamine output. Neither atropine, nifedipine, nor[Lys1,Pro2,5,Arg3,4,Tyr6]-VIP significantly affected the medullary response to VIP. In the presence of PACAP-(6-27), however, the catecholamine response to VIP was attenuated by approximately 77% (P < 0.05). The present study suggests that adrenal catecholamine secretion induced by exogenous VIP may be mediated by a PACAP-related mechanism, most probably through a PACAP type I receptor, in anesthetized dogs. The data also indicate that neither muscarinic receptors, VIP-ergic receptors, nor dihydropyridine-sensitive L-type Ca2+ channels are operative in the adrenal catecholamine response to exogenous VIP in vivo.

scholarly journals Bridging Sex-Specific Differences in the CAR-Mediated Hepatocarcinogenesis of Nitrapyrin Using Molecular and Apical Endpoints

2021 ◽  
Vol 3 ◽  
Author(s):  
Lynea Murphy ◽  
Matthew J. LeBaron ◽  
Kamin Johnson ◽  
Reza J. Rasoulpour ◽  
Xiujuan Wang ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Liver Tumors ◽  
Constitutive Androstane Receptor ◽  
Nitrification Inhibitor ◽  
Tumor Formation ◽  
Male Mice ◽  
Female Mice ◽  
Increased Sensitivity ◽  
Males And Females ◽  
Related Increase

Nitrapyrin, a nitrification inhibitor, produces liver tumors in B6C3F1 mice. In a 2-year oncogenicity study, increased incidence of mice with hepatocellular tumors was observed following exposure to 125 (females only) or 250 mg/kg/day (males and females) nitrapyrin in the diet. Previous data was generated in male mice to support a mode-of-action (MoA) characterized by constitutive androstane receptor (CAR) nuclear receptor (NR) activation, increased hepatocellular proliferation, and subsequent hepatocellular foci and tumor formation. Uncertainty as to the relevance of this MoA for females remained given the increased sensitivity to tumor formation in female mice. A targeted MoA study was conducted to evaluate CAR activation and hepatic responses in female mice treated with the female carcinogenic dose of nitrapyrin for 4 days. Nitrapyrin induced a treatment-related increase in hepatocellular hypertrophy and hepatocellular proliferation. Nitrapyrin also induced a dose-related increase in the Cyp2b10/CAR-associated transcript and liver weights. Nitrapyrin-induced liver weights and Cyp2b10 gene expression for both males and females were compared to data generated from three other established CAR activators; methyl isobutyl ketone, phenobarbital, and sulfoxaflor. The response observed in female mice following exposure to nitrapyrin was within range of the degree of change observed in mice following exposure to tumorigenic doses of other CAR activators. Consistent with the liver MoA in male mice, these data support a CAR-mediated mode of action for nitrapyrin-induced liver tumors in female mice, with the understanding that a focused approach minimizing animal use can bridge male and female datasets when sex-specific carcinogenic differences are observed.

Environmentally Persistent Free Radical Promotes Lung Cancer Progression Via Regulating The Expression Profile of miRNAs

2021 ◽  
Author(s):  
Xiaomin Liu ◽  
Binshu Chai ◽  
Xianyi Wang ◽  
Zong Wu ◽  
Heng Zou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Free Radicals ◽  
Cancer Progression ◽  
Fine Particles ◽  
Health Hazard ◽  
Human Lung Cancer ◽  
Male Mice ◽  
Potential Health ◽  
Female Mice

Abstract Environmentally persistent free radicals (EPFRs) are generated in the combustion processes of solid waste and can cause adverse influences on human health, especially lung diseases. Lung cancer is one of the most serious malignancies in recent years, which the global deaths rate is about 1.6 million every year. However, the mechanism of EPFRs on lung cancer is still not clear. In this study, we verified that ZnO/MCB EPFRs promote cell proliferation and migration, impedes cell apoptosis in lung cancer. Furthermore, we found that ZnO/MCB could influence the expression of miRNAs (miR-18a and miR-34a). In vivo, ZnO/MCB and ZnO EPFRs can reduce the weight and survival rate of BALB/c male mice more than that of BALB/c female mice. In the ZnO/MCB exposed group, male mice lung became even smaller, while the female mice the lung increased significantly. Taken together, our results provide evidence for assessing the potential health risks of persistent free radicals on fine particles. In conclusion, this study linked toxicity of EPFRs with miRNAs revealed the potential health hazard to human lung cancer.

scholarly journals Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice

2002 ◽  
Vol 365 (2) ◽  
pp. 405-416 ◽  
Author(s):  
Simon A. CHANAS ◽  
Qing JIANG ◽  
Michael McMAHON ◽  
Gail K. McWALTER ◽  
Lesley I. McLELLAN ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Leucine Zipper ◽  
Constitutive Expression ◽  
Mutant Mice ◽  
Male Mice ◽  
Glutathione S Transferase ◽  
Glutamate Cysteine Ligase ◽  
Female Mice ◽  
Hepatic Expression ◽  
Increased Sensitivity

Mice that lack the Nrf2 basic-region leucine-zipper transcription factor are more sensitive than wild-type (WT) animals to the cytotoxic and genotoxic effects of foreign chemicals and oxidants. To determine the basis for the decrease in tolerance of the Nrf2 homozygous null mice to xenobiotics, enzyme assay, Western blotting and gene-specific real-time PCR (TaqMan®) have been used to examine the extent to which hepatic expression of GSH-dependent enzymes is influenced by the transcription factor. The amounts of protein and mRNA for class Alpha, Mu and Pi glutathione S-transferases were compared between WT and Nrf2 knockout (KO) mice of both sexes under both constitutive and inducible conditions. Among the class Alpha and class Mu transferases, constitutive expression of Gsta1, Gsta2, Gstm1, Gstm2, Gstm3, Gstm4 and Gstm6 subunits was reduced in the livers of Nrf2 mutant mice to between 3% and 60% of that observed in WT mice. Induction of these subunits by butylated hydroxyanisole (BHA) was more marked in WT female mice than in WT male mice. TaqMan® analyses showed the increase in transferase mRNA caused by BHA was attenuated in Nrf2−/− mice, with the effect being most apparent in the case of Gsta1, Gstm1 and Gstm3. Amongst class Pi transferase subunits, the constitutive hepatic level of mRNA for Gstp1 and Gstp2 was not substantially affected in the KO mice, but their induction by BHA was dependent on Nrf2; this was more obvious in female mutant mice than in male mice. Nrf2 KO mice exhibited reduced constitutive expression of the glutamate cysteine ligase catalytic subunit, and, to a lesser extent, the expression of glutamate cysteine ligase modifier subunit. Little variation was observed in the levels of glutathione synthase in the different mouse lines. Thus the increased sensitivity of Nrf2−/− mice to xenobiotics can be partly attributed to a loss in constitutive expression of multiple GSH-dependent enzymes, which causes a reduction in intrinsic detoxification capacity in the KO animal. These data also indicate that attenuated induction of GSH-dependent enzymes in Nrf2−/− mice probably accounts for their failure to adapt to chronic exposure to chemical and oxidative stress.

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