Age- and gender-related changes in glucose homeostasis in glucocorticoid-treated rats

2014 ◽  
Vol 92 (10) ◽  
pp. 867-878 ◽  
Author(s):  
Cristiane dos Santos ◽  
Francielle Batista D. Ferreira ◽  
Luiz M. Gonçalves-Neto ◽  
Sebastião Roberto Taboga ◽  
Antonio Carlos Boschero ◽  
...  

The disruption to glucose homeostasis upon glucocorticoid (GC) treatment in adult male rats has not been fully characterized in older rats or in females. Thus, we evaluated the age- and gender-related changes in glucose homeostasis in GC-treated rats. We injected male and female rats at 3 months and 12 months of age with either dexamethasone (1.0 mg/kg body mass, intraperitoneally) or saline, daily for 5 days. All of the GC-treated rats had decreased body mass and food intake, and adrenal hypotrophy. Increased glycemia was observed in all of the GC-treated groups and only the 3-month-old female rats were not glucose intolerant. Dexamethasone treatment resulted in hyperinsulinemia and hypertriacylglyceridemia in all of the GC-treated rats. The glucose-stimulated insulin secretion (GSIS) was higher in all of the dexamethasone-treated animals, but it was less pronounced in the older animals. The β-cell mass was increased in the younger male rats treated with dexamethasone. We conclude that dexamethasone treatment induces glucose intolerance in both the 3- and 12-month-old male rats as well as hyperinsulinemia and augmented GSIS. Three-month-old female rats are protected from glucose intolerance caused by GC, whereas 12-month-old female rats developed the same complications that were present in 3- and 12-month-old male rats.

1989 ◽  
Vol 257 (4) ◽  
pp. R700-R704 ◽  
Author(s):  
R. B. McDonald ◽  
C. Day ◽  
K. Carlson ◽  
J. S. Stern ◽  
B. A. Horwitz

Previous investigations have shown that during cold exposure 24-mo-old male Fischer 344 (F344) rats do not thermoregulate as well as do 12-mo-old animals. To determine if this deficiency also occurs in female rats, we measured oxygen consumption (thermogenesis) and colonic temperature of male and female rats 5, 23, and 27 mo of age at rest and during 6 h of exposure to 6 degrees C. In addition, nonshivering thermogenesis (NST) was evaluated from the capacity of brown adipose tissue (BAT) mitochondria isolated from cold-exposed rats to bind guanosine 5'-diphosphate (GDP). Neither age nor gender had a significant effect on resting or cold-exposed oxygen consumption expressed on a mass-independent basis (l/kg body mass0.67) or on a lean body mass independent basis (l/kg lean body mass0.67). The drop in colonic temperature in response to cold was greater in the male rats. However, females exhibited increased BAT mass and relatively constant GDP binding with advancing age, whereas males showed decreased mass and GDP binding. Although the data suggest greater NST capacity in the female rats, rates of cold-induced oxygen consumption were similar in older female vs. male rats. Taken together, our data indicate that gender has a significant impact on thermoregulation and that, under the cold exposure conditions of the study, this effect involves differential heat conservation rather than heat production.


Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 137-146 ◽  
Author(s):  
Victor Viau ◽  
Brenda Bingham ◽  
Jennifer Davis ◽  
Patricia Lee ◽  
Margaret Wong

Individual variations in hypothalamic-pituitary-adrenal (HPA) function are most evident at or beyond the time of puberty, when marked changes in sex steroid release occur. To explore the nature by which gender differences in HPA function emerge we examined in prepubertal (∼30-d-old) and postpubertal (∼60-d-old) male and female rats HPA activity under basal conditions and in response to 30 min of restraint. Within the ACTH-regulating, medial parvocellular portion of the paraventricular nucleus, restraint-induced Fos protein and arginine vasopressin heteronuclear RNA were lower in 60- than in 30-d-old males. No such age-related shift in the response of these synaptic and transcriptional markers of cellular activation occurred in female rats. Basal CRH mRNA expression levels in the paraventricular nucleus increased with age in female but not male rats. Conversely, only male rats showed an age-related increase in basal CRH mRNA in the central amygdala, suggesting that neuronal and neurosecretory CRH-expressing cell types are subject to different pubertal and gender influences. We conclude that gonadal regulation of the HPA axis develops via distinct mechanisms in males and females. Puberty-related shifts in parvocellular neurosecretory function in males are emphasized by stress-induced shifts in neuronal activation, whereas biosynthetic alterations dominate in female rats.


1996 ◽  
Vol 271 (5) ◽  
pp. H1840-H1848 ◽  
Author(s):  
C. Y. Chen ◽  
S. E. DiCarlo

The influence of daily spontaneous running (DSR) and gender on the arterial baroreflex regulation of heart rate (HR) and lumbar sympathetic nerve activity (LSNA) was examined in 13 male [7 sedentary (SED) and 6 DSR] and 12 female (6 SED and 6 DSR) Sprague-Dawley rats. After 8-9 wk of DSR or SED control, all animals were chronically instrumented with right femoral venous and left carotid arterial catheters and electrodes around the lumbar sympathetic trunk. DSR resulted in an increase in heart weight-to-body weight ratio (P = 0.001) in male and female rats and resting bradycardia in male rats (P = 0.001). Arterial baroreflex function was examined by ramp increases (1.25 +/- 0.07 mmHg/s) and decreases (1.47 mmHg/s) in arterial pressure. DSR attenuated the arterial baroreflex regulation of LSNA in a similar manner in female and male rats. DSR reduced the range (32 and 29% for female and male rats, respectively), maximum (26 and 21% for female and male rats, respectively), and maximum gain (Gmax; 46 and 17% for female and male rats, respectively). In contrast, there was a gender influence on the arterial baroreflex regulation of HR. For example, SED female rats had a higher Gmax (40%) than SED male rats. Furthermore, DSR altered the arterial baroreflex regulation of HR differently in male and female rats. DSR female rats had a reduced Gmax (38%), range (25%), and maximum (12%), whereas DSR male rats had a reduced maximum (17%) and minimum (23%). These results demonstrate that DSR attenuated the arterial baroreflex regulation of LSNA in a similar manner in female and male rats. In contrast, DSR altered the arterial baroreflex regulation of HR differently in female and male rats.


2001 ◽  
Vol 91 (6) ◽  
pp. 2831-2838 ◽  
Author(s):  
A. G. Zabka ◽  
M. Behan ◽  
G. S. Mitchell

Age affects time-dependent respiratory responses to episodic hypoxia in male rats, particularly long-term facilitation (LTF), a serotonin-dependent respiratory “memory” [Zabka AG, Behan M, and Mitchell GS, J Physiol (Lond) 531: 509, 2001]. Because age and gender influence serotonergic function, we tested the hypotheses that the short-term hypoxic response (STHR), posthypoxia frequency decline (PHFD) and LTF of phrenic and hypoglossal (XII) motor output change with age and stage of the estrus cycle in female rats. Young (3–4 mo) and middle-aged (13 mo) female Sprague-Dawley rats were anesthetized, paralyzed, vagotomized, and ventilated. STHR was measured during and PHFD after the first of three 5-min episodes of isocapnic hypoxia (arterial Po 2 35–45 Torr). LTF was assessed 60 min postepisodic hypoxia. Phrenic and XII STHR increased with age ( P < 0.05). PHFD was unaffected by age or gender. Phrenic LTF increased with age in both estrus and diestrus ( P < 0.05), whereas XII LTF increased in middle-aged female rats during diestrus only. Age and gender influence time-dependent hypoxic phrenic and XII responses in a complex manner.


Author(s):  
Alexandre A. da Silva ◽  
Mark A. Pinkerton ◽  
Frank T. Spradley ◽  
Ana C. Palei ◽  
John E. Hall ◽  
...  

Previous studies using male rodents showed the adipocyte-derived hormone leptin acts in the brain to regulate cardiovascular function, energy balance and glucose homeostasis. The importance of sex differences in cardiometabolic responses to leptin, however, is still unclear. We examined potential sex differences in leptin's chronic central nervous system (CNS)-mediated actions on blood pressure (BP), heart rate (HR), appetite, and glucose homeostasis in normal and type 1 diabetic rats. Female (n=6) and male (n=5) Sprague-Dawley rats were instrumented with intracerebroventricular (ICV) cannulas for continuous 7-day leptin infusion (15 mg/day) and BP and HR were measured by telemetry 24-hrs/day. At baseline, females had lower MAP (96±3 vs. 104±4 mmHg, p<0.05) but higher HR (375±5 vs. 335±5 bpm, p<0.05) compared to males. Following leptin treatment, we observed similar changes in BP (~3 mmHg) and HR (~25 bpm) in both sexes. Females had significantly reduced body weight (BW, 283±2 vs. 417±7 g, p<0.05) and lower caloric intake (162±20 vs. 192±9 kcal/kg of BW, p<0.05) compared to males, and leptin infusion reduced BW (-10%) and caloric intake (-62%) similarly in both sexes. Leptin infusion also caused similar reductions in fasting insulin and blood glucose levels in both sexes. In female and male rats with streptozotocin-induced diabetes (n=5/sex), ICV leptin treatment for 7 days completely normalized glucose levels. These results show that leptin's CNS effects on BP, HR, glucose regulation and energy homeostasis are similar in male and female rats. Therefore, our results provide no evidence for sex differences in leptin's brain-mediated cardiovascular or metabolic actions.


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.


Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Łukasz Kurach ◽  
Agnieszka Michalak ◽  
Anna Boguszewska-Czubara ◽  
...  

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.


1983 ◽  
Vol 64 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Maurizio Muraca ◽  
Jan De Groote ◽  
Johan Fevery

1. Hepatic bilirubin UDP-glucuronosyltransferase activity was higher in female than in male rats; gonadectomy decreased enzyme activity in females and increased it in males. This sex difference in bilirubin conjugation was further used to evaluate the effect of differences in conjugation on the maximal biliary excretion of bilirubin in the non-anaesthetized rat. 2. After infusion of bilirubin, the maximal biliary excretory rate (Tm) and maximal concentration of bilirubin in bile were respectively 70% and 40% higher in female than in male rats; these values were decreased in females after ovariectomy and increased in males after orchiectomy. A linear relationship was found (r = 0.86; P < 0.001) between bilirubin Tm and hepatic bilirubin UDP-glucuronosyltransferase activity in the four groups of rats, suggesting that conjugation was the rate-limiting step for the maximal hepatic transport of bilirubin. 3. At the end of bilirubin infusion, bilirubin conjugates in serum, determined by alkaline methanolysis and high-performance liquid chromatography, ranged from 0.5 to 1.4% of total bilirubin. Therefore no significant reflux of conjugated bilirubin occurred during saturation of the hepatic transport of the pigment, once more suggesting that the secretory step was not rate-limiting. 4. The composition of bilirubin conjugates in bile was similar in the four groups of rats, despite significant differences in transferase activity. This suggests that the relative proportion of bilirubin mono- and di-conjugates in bile is affected by factors other than transferase activity alone. Relatively more monoconjugates were excreted under the bilirubin load than in basal conditions.


Sign in / Sign up

Export Citation Format

Share Document