Serafina Fernández

Role of 17β-estradiol administration on insulin sensitivity in the rat: implications for the insulin receptor

The role of 17beta-estradiol in the early steps of insulin action is only partially known, although its effect on glucose homeostasis has been reported. In this paper, we attempt to prove the influence of 17beta-estradiol on the insulin receptor of ovariectomized rats treated with different hormonal doses. Our results show that high doses of estradiol impair insulin sensitivity while low doses improve it. We think that these results are the consequence of changes at a molecular level, because high doses of estradiol produced lower expression of the insulin receptor gene, lower content of this receptor in target tissues, and lower phosphorylation of insulin receptor in these tissues. However, low doses of estradiol seem to produce just the opposite. The possible existence of consensus response elements in the insulin receptor gene promoter to estradiol could be controlling the expression of this gene, this control being dose and timing dependent. Moreover, we cannot discard a possible effect of estradiol on the activity of protein tyrosine phosphatases, and therefore, on the activity of the insulin receptor. These new findings improve knowledge about the possible risk for insulin resistance in women taking oral contraceptives or receiving hormonal replacement therapy around the menopause, but could also open the door towards the possible utilization of 17beta-estradiol in some diabetes cases.

Effects of pregnancy on insulin receptor in liver, skeletal muscle and adipose tissue of rats

The mechanism responsible for insulin resistance during pregnancy remains unclear. Considerable evidence indicates that the insulin receptor plays an important role in insulin sensitivity. It seems possible that the hormonal milieu during gestation could have an effect on the insulin receptor. In the present study, measurements of tyrosine phosphorylation and protein content of the insulin receptor and expression of its gene in liver, skeletal muscle and adipose tissue indicate that during pregnancy significant changes occur in these parameters. We found that at the end of early gestation (day 10), muscle and adipose tissue are very sensitive to insulin action because the amount, phosphorylation and gene expression of insulin receptor is higher than in late gestation (days 15–20), while the tissue which is most sensitive to insulin action in late gestation is the liver. Our hypothesis is that these results are connected with changes in the concentrations of estradiol and progesterone observed during pregnancy. In conclusion, our previous and present findings seem to demonstrate that the different concentrations of gestational hormones play an important role in insulin sensitivity in this period and that each tissue responds in the most appropriate manner to guarantee the gestation in its entirety.

Effects of Education on the Quality of Life, Diet, and Cardiovascular Risk Factors in an Elderly Spanish Community Population

An inverse relation between education and health has been reported, suggesting the importance of examining the underlying mechanism of this association. We examined whether cardiovascular risk factors, diet, and indicators of quality of life (mood, self-perceived health, social relationships, self-rated sensory, and dental adequacy) vary according to educational level among 352 old people (65–95 years old) in the city of Oviedo (Northern Spain). Lower educational level (LE) was associated with unhappiness, poor social relationships, poor self-assessed health, and sensory, and masticatory problems. LE elderly consumed less vegetables and meat products and more carbohydrates. LE women had a lower contribution of proteins and lipids to their total energy intake as well as a lower vitamin A intake. Except for hypercholesterolemia, no differencesAn inverse relation between education and health has been reported, suggesting the importance of examining the underlying mechanism of this association. We examined whether cardiovascular risk factors, diet, and indicators of quality of life (mood, self-perceived health, social relationships, self-rated sensory, and dental adequacy) vary according to educational level among 352 old people (65-95 years old) in the city of Oviedo (Northern Spain). Lower educational level (LE) was associated with unhappiness, poor social relationships, poor self-assessed health, and sensory, and masticatory problems. LE elderly consumed less vegetables and meat products and more carbohydrates. LE women had a lower contribution of proteins and lipids to their total energy intake as well as a lower vitamin A intake. Except for hypercholesterolemia, no differences were found for the cardiovascular risk factors studied. The educational level of old people has a strong influence on their quality of life, nutrient intake and food consumption. These findings may provide part of the explanation for the social gradient in mortality.

Independent and interactive association of blood antioxidants and oxidative damage in elderly people.

Oxidative stress is recognized as one of the major contributors to the increased risk of several diseases. Many recent population studies have established a close link between antioxidant defense and lowered risk of morbidity and mortality from cancer and heart disease, but little is known about the cooperative interactions of antioxidants. We examined the cross-sectional independent and interactive association of serum lipid-soluble antioxidant levels and free radical scavenging enzymes to serum malondialdehyde (MDA) levels, as a marker of oxidative damage. The participants were 160 nonsmoker institutionalized elderly. Upper tertile values of erythrocyte-superoxide-dismutase (E-SOD) constituted the strongest-associated single compound with a 74% decreased risk of high MDA. Upper tertiles of carotenoids and f -tocopherol independently showed a similar lowering of risk of about 57%. The highest tertiles of lycopene and either g -carotene or f -tocopherol simultaneously reveal a higher decreased risk for oxidative damage (74 and 71%, respectively), very similar to those in the upper tertiles of all these three vitamins (75%). This study represents one of the few attempts to date to understand the interactive effect between antioxidants and suggests that lipid-soluble antioxidants act not individually, but rather cooperatively with each other. The efficacy of this interaction is more effective when lycopene is present.

Lipid peroxidation, antioxidant status and survival in institutionalised elderly: A five-year longitudinal study

Oxidative stress has been related to ageing and risk of death. To determine whether oxidative status was associated with all-cause risk of death we carried out a prospective study in 154 non-smoking Spanish elderly without major illness. Baseline glutathione peroxidase (GPx) and superoxide dismutase (SOD) were analysed in plasma and erythrocytes. α-tocopherol, β-carotene, lycopene and retinol were determined in serum samples and malondialdehyde (MDA), as a lipid peroxidation marker, in plasma. Mean survival time was 4.3 years. A total of 31 death cases (20.1%) occurred during the follow-up. Plasma-MDA predicted mortality independently of all other variables, while erythrocyte-SOD (e-SOD), β-carotene and α-tocopherol were positively associated with survival. α-tocopherol and MDA were revealed as independent predictors in a joint survival model, being the group with low MDA and high α-tocopherol that with the lowest mortality. In conclusion, a higher risk of death was associated with increased lipid peroxidation and lower antioxidant defenses.

Homocysteine increases the risk of mortality in elderly individuals

Although total plasma homocysteine (tHcy) has been extensively studied as a risk factor of CVD, longitudinal evidence on its association with mortality is scarce, especially among the elderly. The study cohort consisted of 215 subjects (eighty-eight male and 127 female), aged 60 years or older, recruited in fourteen elderly care institutions from Asturias (Spain). All participants were free of major chronic pathology and took no vitamin and/or mineral supplements. Baseline determinations included tHcy in plasma and folate, vitamin B12 and Se in serum. Survival analyses were performed by quintiles of these factors after 6 years (mean follow-up time 4.3 years) by means of Cox regression models. During follow-up time sixty participants died. tHcy above 16.7 micromol/l was associated with an increased risk of mortality in the sample (relative risk 2.30 (95 % CI 1.02, 5.17)). Among the nutritional determinants of tHcy evaluated, folate and Se were not predictive of death risk of the cohort, while vitamin B12 showed inconsistent results. Nevertheless, mortality was significantly lower at higher serum Se levels (upper quintile), but this effect was restricted to women. Higher tHcy in both sexes and lower serum Se in women were found to be independently associated with an increased risk of death in elderly subjects.

Effect of treatment with different doses of 17–β–estradiol on the insulin receptor

The mechanism for the development of insulin resistance in normal pregnancy is complex and is associated with serum levels of sex hormones. However, the influence of these hormones on the early steps of insulin action has not been extensively studied, although the potentially beneficial effect of estradiol on glucose homeostasis has been reported. In this paper, we attempted to determine the effect of 17-beta-estradiol on the insulin receptor of ovariectomized rats treated with different doses of hormones. Our results showed a tissue-dependent response to estradiol. We found that low doses of estradiol increased the amount of insulin receptors in liver and muscle on days 6 and 11 of treatment but not in adipose tissue, and after 16 days only the muscle responsed in this way. On the other hand, high doses of estradiol significantly decreased the amount of insulin receptors, at least in muscle and adipose tissue. We believe that the low concentrations of 17-beta-estradiol (similar to early pregnancy) could be responsible for the increase in insulin sensitivity by increasing the amount of insulin receptors in peripheral tissues. When the hormone levels were high (similar to late pregnancy) the amount of insulin receptors decreased in peripheral tissues, and insulin sensitivity is diminished just as in late pregnancy. The specific molecular mechanism for this action is as yet unknown.

The relationship between dietary lipids and cognitive performance in an elderly population

Abstract Epidemiological studies on the association between diet and cognitive function suggested a possible role of dietary fatty acids in cognitive decline. The aim of the present study was to examine whether intake of different types of fatty acids is associated with cognitive status. A cohort of 304 (127 men and 177 women) institutionalized elderly people, with a mean age of 75.3 ± 6.7 years, were studied. Subjects were evaluated for global cognitive functions (Mini-Mental State Examination [MMSE], Spanish version). Fatty acid intake was assessed with a semi-quantitative food frequency questionnaire. Intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were found to be predictors of cognitive impairment as they were negatively associated with the MMSE score. In accordance with this, fish intake was inversely associated with cognitive impairment. On the contrary, the n-6/n-3 polyunsaturated fatty acid ratio was positively related to the MMSE score. These results could not be explained by differences in age, sex, education, smoking behaviour, inactivity, alcohol, institution or energy intake. We suggest that consumption of EPA and DHA should be encouraged for reducing the risk of cognitive impairment and subsequently disability in elderly people.

Stress and sexual behavior in male rats

Abstract The relationship between sexual behavior and stress in male rats was investigated. Stress induction by psychophysical immobilization fo 3 hours along three days caused significant alterations of the different parameters which make up the sexual behavior of male rats. An extension of the stressing situation from 3 to 6 hours under the same experimental conditions produced very similar sexual disturbances. Our experimental results suggest that effects of acute stress on sexuality may be independent of time.

Dietary intake and biochemical indicators of nutritional status in an elderly Institutionalized and non-institutionalized population

Abstract The nutritional status of 352 elderly men and women, 161 institutionalized and 191 living in their own homes, was assessed. Subjects were free of clinically apparent terminal or wasting illness. Ingestion was evaluated by a food frequency questionnaire. Height, weight, body mass index, triceps skinfold, midarm circumference, mid-arm muscle circumference, mid-arm fat free mass area as well as serum albumin, total serum proteins and total lymphocyte count, were measured. Diet was low in carbohydrates and rich in fat. There was an intake deficiency of vitamins A, C and D. Individuals who were living independently had the highest percentage of inadequate ingestion, with the exception of vitamin C. Institutionalized subjects had less body fat. No differences were found in the biochemical parameters between the two groups, although the percentage of females with mild lymphocyte depletion was higher in the non-institutionalized group. Nutrient intake in northern Spain is similar to other developed countries in Europe.