Relationship among hyperinsulinemia, insulin resistance, and hypertension is dependent on sex

2002 ◽  
Vol 283 (2) ◽  
pp. H562-H567 ◽  
Author(s):  
Denise M. Galipeau ◽  
Linfu Yao ◽  
John H. McNeill

Hyperinsulinemia and insulin resistance have been linked to hypertension; however, the influence of sex on this relationship has not been well studied. The purpose of this experiment was to compare the effects of chronic insulin treatment on insulin sensitivity and blood pressure in male and female rats. Male and female Wistar rats were treated with insulin (2 U/day) via subcutaneous sustained release implants for 5 wk. Systolic blood pressure was measured via the tail-cuff method before and after treatment, and insulin sensitivity was assessed with an oral glucose tolerance test. The insulin sensitivity of female rats was 4.5-fold greater than male rats. Chronic insulin treatment impaired insulin sensitivity in both sexes; however, this occurred to a greater degree in male rats. Blood pressure increased in male rats treated with insulin only. The results demonstrate that hyperinsulinemia and insulin resistance are associated with hypertension in male rats only. Therefore, the link between these conditions appears to depend on sex.

2018 ◽  
Vol 314 (1) ◽  
pp. R12-R21 ◽  
Author(s):  
Hershel Raff ◽  
Brian Hoeynck ◽  
Mack Jablonski ◽  
Cole Leonovicz ◽  
Jonathan M. Phillips ◽  
...  

Care of premature infants often requires parental and caregiver separation, particularly during hypoxic and hypothermic episodes. We have established a neonatal rat model of human prematurity involving maternal-neonatal separation and hypoxia with spontaneous hypothermia prevented by external heat. Adults previously exposed to these neonatal stressors show a sex difference in the insulin and glucose response to arginine stimulation suggesting a state of insulin resistance. The current study used this cohort of adult rats to evaluate insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], plasma adipokines (reflecting insulin resistance states), and testosterone. The major findings were that daily maternal-neonatal separation led to an increase in body weight and HOMA-IR in adult male and female rats and increased plasma leptin in adult male rats only; neither prior neonatal hypoxia (without or with body temperature control) nor neonatal hypothermia altered subsequent adult HOMA-IR or plasma adiponectin. Adult male-female differences in plasma leptin were lost with prior exposure to neonatal hypoxia or hypothermia; male-female differences in resistin were lost in the adults that were exposed to hypoxia and spontaneous hypothermia as neonates. Exposure of neonates to daily hypoxia without spontaneous hypothermia led to a decrease in plasma testosterone in adult male rats. We conclude that neonatal stressors result in subsequent adult sex-dependent increases in insulin resistance and adipokines and that our rat model of prematurity with hypoxia without hypothermia alters adult testosterone dynamics.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Wararat Kittikulsuth ◽  
David M Pollock

Endothelin B (ET B ) receptors mediate vasodilation, anti-inflammation and natriuresis, which ultimately contribute to blood pressure control. We previously showed that renal medullary ET B receptor function is maintained in female angiotensin (Ang) II hypertensive rats, while male Ang II hypertensive rats have blunted ET B -induced natriuretic responses. Because female rats are more resistance to blood pressure elevation induced by high salt intake and/or Ang II infusion, we hypothesized that ET B receptors protect female rats against the hypertensive response and renal injury induced by a high salt diet and chronic Ang II infusion compared to males. Male and female rats received Ang II infusion (150 ng/kg/min; sc.) with 4% NaCl for 4 weeks; blood pressure was measured by telemetry. After a week of Ang II infusion with a high salt diet, subsets of both male and female rats received the ET B antagonist, A-192621, at three doses on consecutive weeks (1, 3, and 10 mg/kg/d in food). Male rats had a significantly higher blood pressure compared to females after 4 weeks of Ang II (178±10 vs. 138±10 mmHg; p<0.05). A-192621 resulted in a dose-dependent increase in blood pressure in female Ang II hypertensive rats (167±8 mmHg at 10 mg/kg/d; p<0.05); the increase produced by A-192621 in male Ang II hypertensive rats was not statistically significant (193±10 mmHg). After 4 weeks of Ang II infusion, the level of proteinuria and nephrinuria was higher in male rats compared to female. A-192621 did not further increase urinary excretion of protein or nephrin in both male and female Ang II hypertensive rats. In conclusion, these results support the hypothesis that ET B receptors provide more protection against hypertension during chronic Ang II infusion in female rats compared to male.


2010 ◽  
Vol 88 (7) ◽  
pp. 753-759 ◽  
Author(s):  
Asdghig H. Der-Boghossian ◽  
Sara R. Saad ◽  
Claudine Perreault ◽  
Chantale Provost ◽  
Danielle Jacques ◽  
...  

The aim of this study was to determine whether the jejunal oligopeptide transporter PepT1 is regulated by insulin and whether this regulation is sex-dependent in type 1 diabetic rats. PepT1 expression, real-time polymerase chain reaction, and Western blots were performed using jejunal segments from 4 groups of male and female rats: normal (nondiabetic), insulin-treated nondiabetic, streptozotocin (STZ)-induced diabetic (type 1 diabetes), and insulin-treated diabetic models. Furthermore, the same segments from all groups underwent perfusion to assess uptake of the dipeptide glycylsarcosine through PepT1. Our results showed that insulin treatment of nondiabetic female rats decreased blood glucose level but did not affect nondiabetic male rats. In both male and female diabetic rats, insulin did not completely decrease blood glucose level. Insulin treatment decreased PepT1 mRNA level in nondiabetic male rats and increased mRNA level in nondiabetic female rats without affecting the PepT1 protein level in either sex. Inducing diabetes with STZ increased PepT1 mRNA and protein levels in female rats; however, in diabetic male rats, the increase in mRNA level was accompanied by a decrease in PepT1 protein level. Treatment of diabetic male rats with insulin partially reversed the effect of diabetes on PepT1 mRNA and protein levels, whereas the same treatment completely restored both PepT1 mRNA and protein to control levels in insulin-treated diabetic female rats. In both nondiabetic male and female rats, insulin treatment had no effect on PepT1 influx rate, and STZ treatment decreased the transporter influx rate. Treatment of diabetic male and female rats with insulin significantly increased PepT1 influx rate; however, complete recovery was found only in diabetic female rats. These results clearly show that insulin and diabetes affected blood glucose level as well as PepT1 activity, expression, and protein levels in a sex-dependent manner. These results suggest that a factor, probably estrogen, could be responsible for the sex-dependent effects of diabetes and insulin in PepT1 level and activity.


2002 ◽  
Vol 283 (6) ◽  
pp. H2478-H2484 ◽  
Author(s):  
Denise Galipeau ◽  
Subodh Verma ◽  
John H. McNeill

The objective of this study was to determine whether the effects of a fructose diet, which causes hyperinsulinemia, insulin resistance, and hypertension in male rats, are dependent on sex. Blood pressure was measured via the tail-cuff method, and oral glucose tolerance tests were performed to assess insulin sensitivity. Blood pressure in female rats did not differ between fructose-fed and control rats at any time point (126 ± 5 and 125 ± 3 mmHg at week 9 for fructose-fed and control rats, respectively) nor was there a difference in any metabolic parameter measured. Furthermore, the vascular insulin resistance that is present in male fructose-fed rats was not observed. After ovariectomy, fructose caused a significant change in systolic blood pressure from baseline compared with fructose-fed ovary-intact rats (change of 21 ± 5 vs. −2 ± 4 mmHg). The results demonstrate that females do not develop hypertension or hyperinsulinemia upon fructose feeding except after ovariectomy, suggesting that female sex hormones may confer protection against the effects of a fructose diet.


2013 ◽  
Vol 65 (2) ◽  
pp. 455-464 ◽  
Author(s):  
G. Koricanac ◽  
Ana Djordjevic ◽  
Zorica Zakula ◽  
Danijela Vojnovic-Milutinovic ◽  
Snezana Tepavcevic ◽  
...  

We analyzed the effects of a fructose-rich diet (FRD) to test the assumption that the expression of metabolic syndrome phenotype is different in male and female rats. Two-way ANOVA revealed a significant effect of FRD on feeding behavior and carbohydrate/lipid metabolism. The increased caloric intake in FRD rats of both sexes was followed by a cluster of gender-specific changes typical for the metabolic syndrome. Female rats were characterized by decreased glycemia, increased triglycerides, enlarged visceral adipose tissue and increased absolute mass of liver, without changes in systolic blood pressure and insulin sensitivity. In contrast, male rats developed less disturbances in physical and biochemical characteristics, but blood pressure and insulin sensitivity were impaired by FRD. The results emphasize the detrimental effects of fructose consumption on cardiovascular risk and insulin action in males, whereas females are affected by other metabolic disturbances. These results support the idea of gender-dependent differences in the expression of the metabolic syndrome phenotype.


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.


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.


2005 ◽  
Vol 289 (4) ◽  
pp. H1335-H1342 ◽  
Author(s):  
Harish Vasudevan ◽  
Hong Xiang ◽  
John H. McNeill

Differences in gender are in part responsible for the development of insulin resistance (IR) and associated hypertension. Currently, it is unclear whether these differences are dictated by gender itself or by the relative changes in plasma estrogen and/or testosterone. We investigated the interrelationships between testosterone and estrogen in the progression of IR and hypertension in vivo in intact and gonadectomized fructose-fed male rats. Treatment with estrogen significantly reduced the testosterone levels in both normal chow-fed and fructose-fed rats. Interestingly, fructose feeding induced a relative increase in estradiol levels, which did not affect IR in both intact and gonadectomized fructose-fed rats. However, increasing the estrogen levels improved insulin sensitivity in both intact and gonadectomized fructose-fed rats. In intact males, fructose feeding increased the blood pressure (140 ± 2 mmHg), which was prevented by estrogen treatment. However, the blood pressure in the fructose-fed estrogen rats (125 ± 1 mmHg) was significantly higher than that of normal chow-fed (113 ± 1 mmHg) and fructose-fed gonadectomized rats. Estrogen treatment did not affect the blood pressure in gonadectomized fructose-fed rats (105 ± 2 mmHg). These data suggest the existence of a threshold value for estrogen below which insulin sensitivity is unaffected. The development of hypertension in this model is dictated solely by the presence or absence of testosterone. In summary, the development of IR and hypertension is governed not by gender per se but by the interactions of specific sex hormones such as estrogen and testosterone.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Maryam Malek ◽  
Mehdi Nematbakhsh

Background. Angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor (ACE2/Ang-1-7/MasR) appears to counteract most of the deleterious actions of angiotensin-converting enzyme/angiotensin II/angiotensin II receptor 1 (ACE/Ang II/AT1R) in renal ischemia/reperfusion (I/R) injury but ACE2 activity and its levels are sexually dimorphic in the kidney. This study was designed to evaluate the effects of activation endogenous ACE2 using the diminazene aceturate (DIZE) in renal I/R injury in male and female rats.Methods. 36 Wistar rats were divided into two groups of male and female and each group distinct to three subgroups (n=6). I/R group was subjected to 45 min of bilateral ischemia and 24 h of reperfusion, while treatment group received DIZE (15 mg/kg/day) for three days before the induction of I/R. The other group was assigned as the sham-operated group.Results. DIZE treatment in male rats caused a significant decrease in blood urea nitrogen (BUN), creatinine, liver functional indices, serum malondialdehyde (MDA), and increase kidney nitrite levels (P<0.05), and in female rats a significant increase in creatinine and decrease serum nitrite levels compared to the I/R group (P<0.05).Conclusions. DIZE may protect the male kidney from renal I/RI through antioxidant activity and elevation of circulating nitrite level.


Sign in / Sign up

Export Citation Format

Share Document