Acute hepatitis due to olmesartan: an uncommon entity.

We report the case of a hypertensive 54-year-old female who had been under treatment with olmesartan (40 mg daily) for a month. She was referred due to hypertransaminasemia and also reported asthenia and a 7 kg weight loss.

Modifiable risk factors associated with prediabetes in men and women: a cross-sectional analysis of the cohort study in primary health care on the evolution of patients with prediabetes (PREDAPS-Study).

BACKGROUND: Prediabetes is a high-risk state for diabetes development, but little is known about the factors associated with this state. The aim of the study was to identify modifiable risk factors associated with the presence of prediabetes in men and women. METHODS: Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS-Study) is a prospective study on a cohort of 1184 subjects with prediabetes and another cohort of 838 subjects without glucose metabolism disorders. It is being conducted by 125 general practitioners in Spain. Data for this analysis were collected during the baseline stage in 2012. The modifiable risk factors included were: smoking habit, alcohol consumption, low physical activity, inadequate diet, hypertension, dyslipidemia, and obesity. To assess independent association between each factor and prediabetes, odds ratios (ORs) were estimated using logistic regression models. RESULTS: Abdominal obesity, low plasma levels of high-density lipoprotein cholesterol (HDL-cholesterol), and hypertension were independently associated with the presence of prediabetes in both men and women. After adjusting for all factors, the respective ORs (95% Confidence Intervals) were 1.98 (1.41-2.79), 1.88 (1.23-2.88) and 1.86 (1.39-2.51) for men, and 1.89 (1.36-2.62), 1.58 (1.12-2.23) and 1.44 (1.07-1.92) for women. Also, general obesity was a risk factor in both sexes but did not reach statistical significance among men, after adjusting for all factors. Risky alcohol consumption was a risk factor for prediabetes in men, OR 1.49 (1.00-2.24). CONCLUSIONS: Obesity, low HDL-cholesterol levels, and hypertension were modifiable risk factors independently related to the presence of prediabetes in both sexes. The magnitudes of the associations were stronger for men than women. Abdominal obesity in both men and women displayed the strongest association with prediabetes. The findings suggest that there are some differences between men and women, which should be taken into account when implementing specific recommendations to prevent or delay the onset of diabetes in adult population.

[Clinical practice guideline for the diagnosis and treatment of hyperprolactinemia]. / Guía de práctica clínica para el diagnóstico y tratamiento de la hiperprolactinemia.

BACKGROUND: Hyperprolactinemia is a common finding within clinical practice in both endocrinology and general practice fields, amongst other specialties. The general practitioner and other specialists must know the indications and serum prolactin determination parameters in order to, once detected, derive the patient for a correct assessment and begin treatment. OBJECTIVE: Formulate a clinical practice guideline evidence-based for the diagnosis and treatment of hyperprolactinemia. METHOD: It took the participation of eight gynecologists, two pathologists and a pharmacologist in the elaboration of this guideline due their experience and clinical judgement. These recommendations were based upon diagnostic criteria and levels of evidence from treatment guidelines previously established, controlled clinical trials and standardized guides for adolescent and adult population with hyperprolactinemia. RESULTS: During the conformation of this guideline each specialist reviewed and updated a specific topic and established the evidence existent over different topics according their field of best clinical expertise, being enriched by the opinion of other experts. At the end, all the evidence and decisions taken were unified in the document presented here. CONCLUSIONS: It is presented the recommendations established by the panel of experts for diagnosis and treatment of patients with high levels of prolactin; also the level of evidence for the diagnosis of hyperprolactinemia, handling drug-induced hyperprolactinemia and prolactinomas in pregnant and non-pregnant patients.

Differential socioemotional and educational profiles in early childhood and primary education students in a lockdown situation.

Recent lockdown situations have highlighted social relationship deprivation of schoolchildren and the need to develop the teaching-learning process in informal contexts. The aim of this study was to analyze differential socioemotional and educational profiles in Early Childhood and Primary Education students using variables relating to academic performance during the COVID-19 pandemic. Correlational, descriptive, and inferential statistical analyses were performed that yielded differential explanatory models depending on the stage of education. The results reveal statistically significant differences in all the variables except for family-school relationship. In the linear regression models, the most statistically significant variable for school performance in both stages was family-school relationship. However, differences were found between both profiles: emotional impact for Early Childhood Education students and social impact for Primary Education students. Lastly, leisure activities at home were included as an explanatory variable only in the Primary Education regression model. The final conclusions highlight the need to attend to the evolutionary characteristics of students in each stage to improve school performance in similar lockdown situations.

Novel Titanocene Y derivative with albumin affinity exhibits improved anticancer activity against platinum resistant cells.

The antitumor activity of Ti(IV)-based compounds put them in the spotlight for cancer treatment in the past, but their lack of stability in vivo due to a high rate of hydrolysis has hindered their development as antitumor drugs. As a possible solution for this problem, we have reported a synthesis strategy through which we combined a titanocene fragment, a tridentate ligand, and a long aliphatic chain. This strategy allowed us to generate a titanium compound (Myr-Ti) capable of interacting with albumin, highly stable in water and with cytotoxic activity in tumor cells[1]. Following a similar strategy, now we report the synthesis of a new compound (Myr-TiY) derived from titanocene Y that shows antitumoral activity in a cisplatin resistant model with a 50% inhibitory concentration (IC50) of 41-76 µM. This new compound shows high stability and a strong interaction with human serum albumin. Myr-TiY has a significant antiproliferative and proapoptotic effect on the tested cancer cells and shows potential tumor selectivity when assayed in non-tumor human epithelial cells being more selective (1.3-3.8 times) for tumor cells than cisplatin. These results lead us to think that the described synthesis strategy could be useful to generate compounds for the treatment of both cisplatin-sensitive and cisplatin-resistant cancers.

Biological evaluation of carbohydrate-based aprepitant analogs for neuroblastoma treatment.

Different studies using Aprepitant, a NK1R antagonist currently used as a clinical drug for treating chemotherapy-related nausea and vomiting, have demonstrated that pharmacological inhibition of NK1R effectively reduces the growth of several tumor types such as neuroblastoma (NB). In a previous work, we demonstrated that a series of carbohydrate-based Aprepitant analogs, derived from either d-galactose or l-arabinose, have shown high affinity and NK1R antagonistic activity with a broad-spectrum anticancer activity and an important selectivity. In this new study, we explore the selective cytotoxic effects of these derivatives for the treatment of NB. Furthermore, we describe the design and stereoselective synthesis of a new generation of d-glucose derivatives as Aprepitant analogs, supported by docking studies. This approach showed that most of our carbohydrate-based analogs are significantly more selective than Aprepitant. The galactosyl derivative 2α, has demonstrated a marked in vitro selective cytotoxic activity against NB, with IC50 values in the same range as those of Aprepitant and its prodrug Fosaprepitant. Interestingly, the derivative 2α has shown similar apoptotic effect to that of Aprepitant. Moreover, we can select the glucosyl amino derivative 10α as an interesting hit exhibiting higher in vitro cytotoxic activity against NB than Aprepitant, being 1.2 times more selective.

A new time limited psychotherapy for BPD: preliminary results of a randomized and controlled trial.

INTRODUCTION: Psychic Representation focused Psychotherapy (PRFP) is a new time limited dynamic psychotherapy for the treatment of Borderline Personality Disorder. It is a psychodynamic technique based on brief psychoanalytic psychotherapy principles. It is manualized and designed to be applied in the framework of public health care services. A randomized and controlled study with a sample of 53 patients was conducted to assess PRFP efficacy. This work presents the results for the first 44 trial completers at termination of treatment. METHODS: Both groups, the experimental (n= 18) and control group (n= 26), received treatment as usual. The experimental group received an additional 20 (PRFP) sessions, conducted by four therapists with homogenous characteristics specifically trained in this technique. The main outcome variables measures were: Severity global index of SCL-90-R, Barrat Impulsivity Scale scores and Social Adaptation (SASS score). Baseline and final condition at termination was compared. CONCLUSIONS: Preliminary results showed significantly better outcomes for the experimental group in all the main variables measured and in most of the secondary ones. PRFP may represent an important contribution for the treatment of BPD patients. Follow-up assessment at 6 and 12 months is planned.

[Results of the Implementation of a Case-Finding Program for Alpha-1 Antitrypsin Deficiency in COPD Patients]. / Resultados de la implementación de un programa de detección de casos de déficit de alfa-1 antitripsina en pacientes con EPOC.

Objectives: Currently, the identification of new cases of alpha-1 antitrypsin deficiency (AATD) continues to be one of the great challenges facing the disease. The present study aims to perform an analysis of the results of the implementation of a systematic case detection program of AATD for patients with chronic obstructive pulmonary disease. Material and methods: Cross-sectional observational study in which the results of AAT screening until December 2022 were analyzed. The cases studied were divided into three periods: (1) no systematic case detection until 2013; (2) systematic case detection of S and Z alleles for cases with AAT < 90 mg/dL until 2018, and (3) systematic case detection of 14 mutations for cases with AAT < 120 mg/dL since 2018. Results: A total of 471 cases were studied, of which 306 (65.0%) were carriers of some mutation related to HAD. The number of detected cases of all mutations with their percentage against those studied in each period was respectively: 6 (100%), 48 (88.8%) and 253 (61.5%). If we limit to severe mutations (AAT < 57.2 mg/dL), the distribution by periods was respectively: 3 (50.0), 10 (18.5%) and 17 (4.1%). Conclusions: The present study describes the changes in the detection of patients carrying DAAT-related alleles with three different case identification policies. The data support the use of systematic case detection system in the COPD patient population.

[Influence of learning styles of nursing students on teaching strategies choice]. / Elección de estrategias de enseñanza. Influencia de los estilos de aprendizaje del alumnado de enfermería.

The objective of this research focuses on the framework of teaching strategies, by acknowledging learning styles as first determination and, in relation to the changes that these are going through, identifying the teaching strategies best rated and preferred by the students. This is a prospective open cohort study with the students of Nursing Diploma 2007/2010 of the Universidad de Córdoba. Once the population was identified in the first year (first analysis), annual measurings were undertaken every year during their training. In order to study the learning styles, the questionnaire CHAEA was administered and a scale from 1 to 10 (1 = highest, 10 = lowest) was used to determine the preferences for learning strategies. The results show the variability of the learner (up to 11 styles). However, the dominant style is the reflective, followed by the theoretical and the pragmatic. The least developed was the active style. As the years of training go by, a tendency towards a dual style (reflective-theoretical) can be observed. In relation to teaching strategies, the preferred ones were those set in professional areas, workshops and debates. Relevant changes were also seen as they advanced in their training. The results establish a specific significant relationship between learning styles and teaching strategies.

Mesoamerican nephropathy: A not so unknown chronic kidney disease.

From 2000, Mesoamerican region has reached an important rate of chronic kidney disease of unknown etiology. Under the name of Meroamerican Nephropathy (MeN) several hypotheses (including dehydration, heat stress, environmental or toxic exposure or even infections) have tried to explain the etiology this new disease. MeN affects young men, agricultural workers exposed to high temperatures. MeN courses with unspecific symptoms as low-grade fever and dysuria and progressive kidney disease with impaired renal function and hydroelectrolyte disturbances. The diagnosis requires kidney biopsy showing tubule-interstitial nephritis (usually at chronic stage). Although MeN conditions a high morbi-mortality in endemic regions, there is a lack of specific treatment and only preventive measures have demonstrated some effect of prognosis (avoid heat stress, constant hydration). In this review we aim to summarize the available information of MeN, illustrating the information in a case report.

New titanocene derivative with improved stability and binding ability to albumin exhibits high anticancer activity.

Titanium-based therapies have emerged as a promising alternative for the treatment of cancer patients, particularly those with cisplatin resistant tumors. Unfortunately, some titanium compounds show stability and solubility problems that have hindered their use in clinical practice. Here, we designed and synthesized a new titanium complex containing a titanocene fragment, a tridentate ligand to improve its stability in water, and a long aliphatic chain, designed to facilitate a non-covalent interaction with albumin, the most abundant protein in human serum. The stability and human serum albumin affinity of the resulting titanium complex was investigated by UV-Vis absorption and fluorescence spectroscopy techniques. Complex [TiCp2{(OOC)2py-O-myr}] (3) (myr = C14H29, py = pyridine) and its analogous [TiCp2{(OOC)2py-OH}] (4), lacking the aliphatic chain, showed improved stability in phosphate saline buffer compared with [TiCp2Cl2] (1). 3 showed a strong interaction with human serum albumin in a 1:1 stoichiometry. The cytotoxic effect of 3 was higher compared to [TiCp2Cl2] in tumor cell lines and showed potential tumor selectivity when assayed in non-tumor human epithelial cells. Finally, 3 showed an antiproliferative effect on cancer cells, decreasing the population in the S phase, and increasing apoptotic cells in a significant manner. All this makes the novel Ti(IV) compound 3 a firm candidate to continue further studies of its therapeutic potential in vitro and in vivo.

Mesoamerican nephropathy: A not so unknown chronic kidney disease. / Nefropatía endémica mesoamericana: una enfermedad renal crónica de origen no tan desconocido.

From 2000, Mesoamerican region has reached an important rate of chronic kidney disease of unknown etiology. Under the name of Meroamerican Nephropathy (MeN) several hypotheses (including dehydration, heat stress, environmental or toxic exposure or even infections) have tried to explain the etiology this new disease. MeN affects young men, agricultural workers exposed to high temperatures. MeN courses with unspecific symptoms as low-grade fever and dysuria and progressive kidney disease with impaired renal function and hydroelectrolyte disturbances. The diagnosis requires kidney biopsy showing tubule-interstitial nephritis (usually at chronic stage). Although MeN conditions a high morbi-mortality in endemic regions, there is a lack of specific treatment and only preventive measures have demonstrated some effect of prognosis (avoid heat stress, constant hydration). In this review we aim to summarize the available information of MeN, illustrating the information in a case report.

The heterogeneity of reversion to normoglycemia according to prediabetes type is not explained by lifestyle factors.

Healthy lifestyle interventions and drug therapies are proven to have a positive preventative influence on normal glucose regulation in prediabetes. However, little is known on the specific role that these factors play on reversion to normal glycemia according to type of prediabetes. We used data from the Observational prospective cohort study, The Cohort study in Primary Health Care on the Evolution of Patients with Prediabetes from 2012 to 2015. A total of 1184 individuals aged 30-74 years old were included and classified based on the ADA in three mutually exclusive groups using either fasting plasma glucose (FPG) levels (from 100 to 125 mg/dl, FPG group), HbA1c (5.7-6.4%, HbA1c group) or both impaired parameters. Information on lifestyle factors and biochemical parameters were collected at baseline. Reversion to normal glucose regulation was calculated at third year of follow-up. Relationship of lifestyle factor and type of prediabetes with reversion were estimated using odds ratios (ORs) with 95% confidence intervals (95% CIs) adjusting by different groups of confounders. Proportion of reversion rates were 31% for FPG group, 31% for HbA1c group and 7.9% for both altered parameters group, respectively. Optimal life style factors such as BMI < 25 kg/m2[OR (95% CI): 1.90 (1.20-3.01)], high adherence to Mediterranean diet 1.78 (1.21-2.63) and absence of abdominal obesity 1.70 (1.19-2.43) were the strongest predictors for reversion to normal glucose. However, those did not modify the ORs of reversion to normal glucose. Taking as reference those with both impaired parameters, subjects with FPG impairment (FPG group) had an OR of 4.87 (3.10-7.65) and 3.72 (2.39-5.78) for HbA1c group. These estimates remained almost the same after further adjustment for biochemical parameters and lifestyle factors (4.55(2.84-7.28) and 3.09 (1.92-4.97), respectively). Optimal lifestyle factors showed to be a positive predictor for reversion to normal glucose regulation however, the differences of reversion risk according type of prediabetes are not explained by lifestyle factors.

The effect of aging on insulin signalling pathway is tissue dependent: central role of adipose tissue in the insulin resistance of aging.

Insulin resistance progressively increases with age, resulting in excessively high incidence of T2D in the elderly population. To investigate the molecular mechanisms underlying insulin resistance of aging, we carried out a comparative study of insulin signalling cascade in adipose tissue, liver and skeletal muscle. We measured the protein levels in different subcellular compartments and the phosphorylation status of key components of the insulin signalling pathway in response to in vivo insulin infusion. White adipose tissue (WAT) from old rats shows altered subcellular distribution of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) and a marked reduction in the insulin-stimulated IR tyrosine phosphorylation. Furthermore, activation of Akt, as well as GLUT4 translocation to the plasma membrane, is impaired. Quadriceps muscle from old rats also has a defect in GLUT4 trafficking but, in contrast to WAT, insulin signalling at the level of IR and Akt is increased. In liver, we found no major differences in the ability of insulin to induce autophosphorylation of the IR or activation of Akt between adult and old animals. These data, therefore, show at the molecular level that insulin resistance in adipose tissue precedes the development of liver and muscle insulin resistance in aged rats.

Giant aneurysmal bone cyst of the mandible with unusual presentation.

Aneurysmal bone cysts are rare benign lesions of bone tissue, infrequent in craneofacial skeleton with regard to other structures like long bones or the spine. They are composed of sinusoidal and vascular spaces blood-filled and surrounded by fibrous tissue septa. We present a case of a 29-year-old Caucasian male with a big swelling in the left mandible associated to pain and rapid growth. He referred previous extraction of the left inferior third molar. On the X-ray study, an expansive multilocular and high vascularized bony lesion within the mandibular angle was observed. It produced expansion and destruction of lingual and buccal cortex. An incisional biopsy was performed showing a fibrous tissue with blood-filled spaces lesion suggestive of an aneurysmal bone cyst. After selective embolization of the tumour, surgical resection was done with curettage and immediate reconstruction of the defect with an anterior iliac crest graft. Aneurysmal bone cysts are non-neoplastic but locally aggressive tumours with occasional rapid growth that may be differentiated from other multilocular process like ameloblastoma, ossifying fibroma, epithelial cyst, giant cell granuloma and sarcomas. Treatment of choice consists on conservative surgical excision of the mass with curettage or enucleation. When resection creates a big defect, primary surgical reconstruction is recommended.

Increased thrombin generation after acute versus chronic coronary disease as assessed by the thrombin generation test.

Atherosclerosis is the most common pathophysiologic substrate of coronary artery disease (CAD). Whereas plaque progression and arterial remodeling are critical components in chronic CAD, intracoronary thrombosis over plaque disruption is causally related to acute CAD. It was the objective of this study to investigate the differences between prior acute CAD and chronic CAD by a simple global coagulation assay measuring thrombin generation. A cross-sectional study involving 15 healthy controls, 35 patients with chronic stable CAD, and 60 patients after an episode of acute myocardial infarction (AMI) was performed. Thrombin generation was measured between three and 11 months after the initial diagnosis (mean 6 months) by a commercially available fluorogenic assay (Technothrombin TGA). In each patient the lag phase, velocity index and peak thrombin were obtained from the thrombogram profile. Traditional cardiovascular risk factors were recorded, and the inflammatory markers, fibrinogen and hs-C-reactive protein were determined. Compared with stable CAD patients, showing normal thrombograms, those with previous AMI showed earlier lag phase (p < 0.05) and significant increase of both the velocity index (p < 0.001) and peak thrombin (p < 0.05), indicating faster and higher thrombin generation in the AMI group. Differences in thrombin generation between stable and acute CAD patients remained significant (p < 0.001) after adjusting for conventional CAD risk factors (age, gender, diabetes, hypertension, smoking, and hypercholesterolemia). In conclusion, patients with a previous history of acute CAD showed earlier, faster and higher thrombin generation than stable chronic CAD patients. The thrombin generation test may be of clinical value to monitor hypercoagulable/vulnerable blood and/or guide therapy in CAD.

An update on the biology of cancer stem cells in breast cancer.

Breast cancer stem cells are defined as cancer cells with self-renewal capacity. These cells represent a small subpopulation endowed with the ability to form new tumours when injected in nude mice. Markers of differentiation have been used to identify these cancer cells. In the case of breast cancer, CD44+/CD24- select a population with stem cell properties. The fact that these cells have self-renewal ability has suggested that this population could be responsible for new tumour formation and cancer relapse. These cells have been shown to be more resistant to chemotherapy and radiotherapy than normal cancer cells. The identification of the molecular druggable alterations responsible for the initiation and maintenance of cancer stem cells is an important goal. In this article we will review all these points with special emphasis on the possible role of new drugs designed to interact with molecular pathways of cancer stem cells.

Adiposity and Diabetes Risk in Adults with Prediabetes: Heterogeneity of Findings Depending on Age and Anthropometric Measure.

OBJECTIVE: The study aimed to evaluate the effect of age on diabetes incidence by general and central adiposity after 3-year follow-up in adults with prediabetes. METHODS: Data were taken from a cohort of 1,184 subjects with prediabetes included in The Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS). General adiposity was defined using body mass index (BMI), and central adiposity was defined with waist circumference and waist to height ratio. Data were analyzed by age groups 30 to 59 and 60 to 74 years. The association between adiposity and diabetes incidence was assessed using hazard ratios (HR). RESULTS: Adjusting for sociodemographic characteristics, lifestyles, and metabolic parameters, diabetes HR for central adiposity based on the waist circumference clinical cutoff were 2.14 (1.12-4.09) and 1.48 (0.80-2.74) for people aged 30 to 59 and 60 to 74 years, respectively. In the model additionally adjusted for BMI, diabetes HR were 2.65 (1.24-5.65) and 1.33 (0.68-2.59), respectively. The use of a 1-SD increase rather than cutoff points did not alter this pattern. Similar findings were observed with central adiposity based on waist to height ratio. CONCLUSIONS: The association of central adiposity with type 2 diabetes incidence was lower for people in the older age group than for those in the younger age group.

Association of General and Abdominal Obesity With Hypertension, Dyslipidemia and Prediabetes in the PREDAPS Study.

INTRODUCTION AND OBJECTIVES: Some anthropometric measurements show a greater capacity than others to identify the presence of cardiovascular risk factors. This study estimated the magnitude of the association of different anthropometric indicators of obesity with hypertension, dyslipidemia, and prediabetes (altered fasting plasma glucose and/or glycosylated hemoglobin). METHODS: Cross-sectional analysis of information collected from 2022 participants in the PREDAPS study (baseline phase). General obesity was defined as body mass index ≥ 30kg/m2 and abdominal obesity was defined with 2 criteria: a) waist circumference (WC) ≥ 102cm in men/WC ≥ 88cm in women, and b) waist-height ratio (WHtR) ≥ 0.55. The magnitude of the association was estimated by logistic regression. RESULTS: Hypertension showed the strongest association with general obesity in women (OR, 3.01; 95%CI, 2.24-4.04) and with abdominal obesity based on the WHtR criterion in men (OR, 3.65; 95%CI, 2.66-5.01). Hypertriglyceridemia and low levels of high-density lipoprotein cholesterol showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.49; 95%CI, 1.68-3.67 and OR, 2.70; 95%CI, 1.89-3.86) and with general obesity in men (OR, 2.06; 95%CI, 1.56-2.73 and OR, 1.68; 95%CI, 1.21-2.33). Prediabetes showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.48; 95%CI, 1.85-3.33) and with abdominal obesity based on the WC criterion in men (OR, 2.33; 95%CI, 1.75-3.08). CONCLUSIONS: Abdominal obesity indicators showed the strongest association with the presence of prediabetes. The association of anthropometric indicators with hypertension and dyslipidemia showed heterogeneous results.

Altered subcellular distribution of IRS-1 and IRS-3 is associated with defective Akt activation and GLUT4 translocation in insulin-resistant old rat adipocytes.

Insulin receptor signal transduction depends on the precise intracellular localization of signalling molecules. This study examines the compartmentalization and the insulin-induced translocation and tyrosine phosphorylation of insulin receptor substrates (IRS-1 and IRS-3) in epididymal white adipose tissue from adult and insulin-resistant old rats. We found that insulin induces the translocation of IRS-1 from plasma membrane (PM) and light microsomes (LM) to cytosol, whereas IRS-3 translocates from PM to LM and cytosol upon insulin stimulation. Old rat adipocytes are characterized by higher relative levels of IRS proteins, under basal conditions, in those fractions where they are intended to translocate in response to insulin and exhibit a higher phosphotyrosine content of IRS-1 and -3 in basal conditions and a lower maximal phosphorylation in response to insulin. Furthermore, old rat adipocytes are also characterized by a reduced ability of insulin to stimulate both, Akt/PKB activity and translocation of GLUT4 to the PM. We conclude that the lower stimulation of downstream insulin signalling involved in glucose metabolism in old rat adipocytes may be explained, at least in part, by the altered subcellular distribution of IRS-1 and -3 proteins. In addition, our data suggest that the mechanism of turning on/off insulin receptor-mediated signal is impaired with aging.