Dysregulated zinc homeostasis and microadenomas in the anterior pituitary: pathological insights into suicide risk.

Background: Suicide is a significant public health problem influenced by various risk factors, including dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. Zinc (Zn), essential for pituitary function in hormone synthesis and release, has been linked to suicide, with studies noting reduced serum levels and altered brain transport mechanisms. Despite Zn's crucial role in pituitary function and its involvement in suicidal behavior, information on pituitary Zn in suicide is scarce. Tumor cells modify Zn dynamics in tissues, and a previous report suggests microadenomas in the anterior pituitary as a risk factor for suicide. Methods: Histopathological analysis with hematoxylin-eosin stain and histochemical techniques to assess Zn homeostasis were carried out on anterior pituitary postmortem samples from 14 suicide completers and 9 non-suicidal cases. Results: Pituitary microadenomas were identified in 35% of suicide cases and none in the non-suicidal cases. Furthermore, compartmentalized Zn (detected via dithizone reactivity), but not free Zn levels (detected via zinquin reactivity), was lower in the suicide cases compared to the non-suicidal group. Conclusion: This is the first report of a potential association between disrupted Zn homeostasis and microadenomas in the anterior pituitary as a feature in suicide and provides critical insights for future neuroendocrine Zn-related research.

Hypozincemia in Mexican patients with diabetic foot ulcer treated out of hospital.

OBJECTIVE: To know the frequency of people with hypozincemia in a group of Mexican patients with Diabetic Foot Ulcers (DFU)m and its relationship with metabolic and clinical profile. MATERIAL AND METHODS: Cross-sectional, analytical, and observational study in patients with and without DFU, treated in Family Medicine Units from Instituto Mexicano del Seguro Social (IMSS) in Mérida, Yucatán, México. Frequency of hypozincemia (Zn serum < 70 g/ml) and its relationship with the levels of Glycosylated Hemoglobin (HbA1c), cholesterol and triglycerides was analyzed. RESULTS: 70% of patients with DFU and 25% without DFU had hypozincemia (OR = 5.2, 95% CI 2.139-12.65, p = 0.0004). Patients with hypozincemia were older and the highest prevalence was between 50 and 60 years. The average area of the DFU showed no differences in patients with and without hypozincemia. Patients with DFU reported higher levels of HbA1c, cholesterol, triglycerides, BMI, and blood pressure compared to patients without DFU. Hypozincemia was associated with higher BMI values. CONCLUSION: The frequency of hypozincemia in diabetic patients with UPD is high and is behaving as a risk factor for presenting UPD, so its identification should be routine.

OBJETIVO: Conocer la frecuencia de hipozinquemia en pacientes Mexicanos con úlceras de pie diabético (UPD) y su relacion con el perfil clínico y metabólico. MATERIAL Y MÉTODOS: Estudio transversal, analítico, en pacientes con y sin úlceras de pie diabético, tratados en unidades de medicina familiar del Instituto Mexicano del Seguro Social (IMSS) en Mérida, Yucatán, México, que analizó la frecuencia de Hipozinquemia (Zn serico de < 70 mg/ml) y su relación con los niveles de Hemoglobina Glucosilada (HbA1c), colesterol y triglicéridos. RESULTADOS: 70% de los pacientes con UPD y 25% sin UPD tenían hipoziquemia (OR=5.2, IC95% 2.139-12.65, p=0.0004). La mayor prevalencia se encontró entre los 50 y 60 años. El área promedio de las UPD no mostró diferencias entre pacientes con y sin hipozinquemia. Los pacientes con UPD presentaron niveles más altos de HbA1c (p<0.001), colesterol (p<0.001), triglicéridos (p<0.001), IMC (p=0.01) y tensión arterial (p=0.009) en comparación con los pacientes sin UPD. Los pacientes con UPD e hipoziquemia tenían mayores valores de IMC. CONCLUSIÓN: La frecuencia de hipozinquemia en pacientes diabéticos con UPD es alta y es se comporte como un factor de riesgo para presentar UPD, por lo que su identificación deberia ser rutinaria.

Aortic dysfunction by chronic cadmium exposure is linked to multiple metabolic risk factors that converge in anion superoxide production.

CONTEXT: The chronic exposure to Cadmium (Cd) constitute an risk to develop hypertension and cardiovascular diseases associated with the increase of oxidative stress. OBJECTIVE: In this study, we investigate the role of metabolic changes produced by exposure to Cd on the endothelial dysfunction via oxidative stress. METHODS: Male Wistar rats were exposed to Cd (32.5-ppm) for 2-months. The zoometry and blood pressure were evaluated, also glucose and lipids profiles in serum and vascular reactivity evaluated in isolated aorta rings. RESULTS: Rats exposed to Cd showed an increase of blood pressure and biochemical parameters similar to metabolic syndrome. Additionally, rats exposed to Cd showed a reduced relaxation in aortic rings, which was reversed after the addition of SOD and apocynin an inhibitor of NADPH. CONCLUSION: The Cd-exposition induced hypertension and endothelial injury by that modifying the vascular relaxation and develop oxidative stress via NADPH oxidase, superoxide and loss nitric oxide bioavailability.

Association of Differences in Dietary Behaviours and Lifestyle with Self-Reported Weight Gain during the COVID-19 Lockdown in a University Community from Chile: A Cross-Sectional Study.

Domiciliary confinement of people is one of the main strategies to limit the impact of COVID-19. Lockdowns have led to changes in lifestyle, emotional health, and eating habits. We aimed to evaluate the association of differences in dietary behaviours and lifestyle with self-reported weight gain during the COVID-19 lockdown in Chile. In this cross-sectional analytical study, five previously validated surveys were condensed into a single 86-item online questionnaire. The survey was sent to 1000 potential participants of the university community; it was kept online for 28 days to be answered. Of the 639 respondents, the mean self-reported weight gain during confinement was 1.99 kg (standard deviation [SE]: 0.17) and 0.7 (SE: 0.06) units of body mass index (BMI) (both p < 0.001) and the median difference in body weight during lockdown was 3.3% (interquartile range [IQR]: 0.0-6.7). The differences of intake of most food groups before and during lockdown were associated with greater self-reported weight, BMI and percentage weight gain. Differences in lifestyle (odds ratio [OR] = 14.21, 95% confidence interval [95%CI]: 2.35-85.82) worsening eating habits (OR = 3.43, 95%CI: 2.31-5.09), and more consumption of sweet or filled cookies and cakes during lockdown (OR = 2.11, 95%CI: 1.42-3.13) were associated with self-reported weight gain. In conclusion, different dietary behaviours (mainly consumption of industrialized foods) during lockdown, as well as quality of life deterioration were the main factors associated with self-reported weight gain during lockdown.

Autophagy inhibition in breast cancer cells induces ROS-mediated MIF expression and M1 macrophage polarization.

Autophagy can function as a survival mechanism for cancer cells and therefore, its inhibition is currently being explored as a therapy for different cancer types. For breast cancer, triple negative breast cancer (TNBC) is the subtype most sensitive to the inhibition of autophagy; but its inhibition has also been shown to promote ROS-dependent secretion of macrophage migration inhibitory factor (MIF), a pro-tumorigenic cytokine. In this work, we explore the role of MIF in breast cancer, the mechanism by which autophagy inhibition promotes MIF secretion and its effects on neighboring cancer cell signaling and macrophage polarization. We analyzed MIF mRNA expression levels in tumors from breast cancer patients from different subtypes and found that Luminal B, HER2 and Basal subtypes, which are associated to high proliferation, displayed high MIF levels. However, MIF expression had no prognostic relevance in any breast cancer subtype. In addition, we found that autophagy inhibition in 66cl4 TNBC cells increased intracellular Reactive Oxygen Species (ROS) levels, which increased MIF expression and secretion. MIF secreted from 66cl4 TNBC cells induced the activation of MIF-regulated pathways in syngeneic cell lines, increasing Akt phosphorylation in 4T1 cells and ERK phosphorylation in 67NR cells. Regarding MIF/ chemokine receptors, higher levels of CD74 and CXCR2 were found in TNBC tumor cell lines when compared to non-tumorigenic cells and CXCR7 was elevated in the highly metastatic 4T1 cell line. Finally, secreted MIF from autophagy deficient 66cl4 cells induced macrophage polarization towards the M1 subtype. Together, our results indicate an important role for the inhibition of autophagy in the regulation of ROS-mediated MIF gene expression and secretion, with paracrine effects on cancer cell signaling and pro-inflammatory repercussions in macrophage M1 polarization. This data should be considered when considering the inhibition of autophagy as a therapy for different types of cancer.

Amphetamine sensitization alters hippocampal neuronal morphology and memory and learning behaviors.

It is known that continuous abuse of amphetamine (AMPH) results in alterations in neuronal structure and cognitive behaviors related to the reward system. However, the impact of AMPH abuse on the hippocampus remains unknown. The aim of this study was to determine the damage caused by AMPH in the hippocampus in an addiction model. We reproduced the AMPH sensitization model proposed by Robinson et al. in 1997 and performed the novel object recognition test (NORt) to evaluate learning and memory behaviors. After the NORt, we performed Golgi-Cox staining, a stereological cell count, immunohistochemistry to determine the presence of GFAP, CASP3, and MT-III, and evaluated oxidative stress in the hippocampus. We found that AMPH treatment generates impairment in short- and long-term memories and a decrease in neuronal density in the CA1 region of the hippocampus. The morphological test showed an increase in the total dendritic length, but a decrease in the number of mature spines in the CA1 region. GFAP labeling increased in the CA1 region and MT-III increased in the CA1 and CA3 regions. Finally, we found a decrease in Zn concentration in the hippocampus after AMPH treatment. An increase in the dopaminergic tone caused by AMPH sensitization generates oxidative stress, neuronal death, and morphological changes in the hippocampus that affect cognitive behaviors like short- and long-term memories.

Changes in nitric oxide, zinc and metallothionein levels in limbic regions at pre-pubertal and post-pubertal ages presented in an animal model of schizophrenia.

Recent data suggest that rats with neonatal ventral hippocampal lesion (NVHL) show changes related to inflammatory processes and oxidative stress at the prefrontal cortex (PFC) level at post-pubertal age. The NVHL model is considered an animal model in schizophrenia. Here we analyzed the levels of nitrite, zinc, and metallothionein (MT) in cortical and subcortical regions of NVHL rats at pre-pubertal and post-pubertal ages. Nitric oxide (NO) levels were evaluated through measurement of nitrite levels. The locomotor activity was also evaluated in a novel environment. Animals with NVHL showed an increase in locomotor activity only at post-pubertal age. Furthermore, at pre-pubertal age, NVHL rats showed an increase in NO levels in ventral and dorsal hippocampus, thalamus, Caudate-putamen (CPu) and brainstem, in zinc levels in ventral and dorsal hippocampus, and CPu, and the MT level also in the ventral hippocampus and occipital cortex. In addition, at pre-pubertal age, a reduction in MT levels was also found in the PFC, parietal and temporal cortices, the CPu and the cerebellum. However, after puberty, NVHL caused an increase in NO levels in the PFC, and also zinc levels in the PFC and occipital and parietal cortices, with a reduction in MT levels in the thalamus and NAcc. Our results show the changes of these three molecules over time, among lesion (PD7), pre-pubertal and post-pubertal ages. This suggests changes at pre-pubertal age directly related to the site of the lesion, while at post-pubertal age, our data highlight changes in the PFC, a region mainly involved in schizophrenia.

IMPACT OF COMORBIDITIES IN MEXICAN SARS-COV-2-POSITIVE PATIENTS: A RETROSPECTIVE ANALYSIS IN A NATIONAL COHORT.

BACKGROUND: The coronavirus disease 2019 outbreak is a significant challenge for health-care systems around the world. OBJECTIVE: The objective of the study was to assess the impact of comorbidities on the case fatality rate (CFR) and the development of adverse events in patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Mexican population. MATERIALS AND METHODS: We analyzed the data from 13,842 laboratory-confirmed SARS-CoV-2 patients in Mexico between January 1, 2020, and April 25, 2020. We investigated the risk of death and the development of adverse events (hospitalization, pneumonia, orotracheal intubation, and intensive care unit [ICU] admission), comparing the number of comorbidities of each patient. RESULTS: The patient mean age was 46.6 ± 15.6 years, 42.3% (n = 5853) of the cases were women, 38.8% of patients were hospitalized, 4.4% were intubated, 29.6% developed pneumonia, and 4.4% had critical illness. The CFR was 9.4%. The risk of hospitalization (odds ratio [OR] = 3.1, 95% confidence interval [CI]: 2.7-3.7), pneumonia (OR = 3.02, 95% CI: 2.6-3.5), ICU admission (OR = 2, 95% CI: 1.5-2.7), and CFR (hazard ratio = 3.5, 95% CI: 2.9-4.2) was higher in patients with three or more comorbidities than in patients with 1, 2, or with no comorbidities. CONCLUSIONS: The number of comorbidities may be a determining factor in the clinical course and its outcomes in SARS-CoV-2-positive patients.

Impact of comorbidities in mexican SARS-COV-2-positive patients: a retrospective analysis in a national cohort

ABSTRACT Background: The coronavirus disease 2019 outbreak is a significant challenge for health-care systems around the world. Objective: The objective of the study was to assess the impact of comorbidities on the case fatality rate (CFR) and the development of adverse events in patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Mexican population. Materials and methods: We analyzed the data from 13,842 laboratory-confirmed SARS-CoV-2 patients in Mexico between January 1, 2020, and April 25, 2020. We investigated the risk of death and the development of adverse events (hospitalization, pneumonia, orotracheal intubation, and intensive care unit [ICU] admission), comparing the number of comorbidities of each patient. Results: The patient mean age was 46.6 ± 15.6 years, 42.3% (n = 5853) of the cases were women, 38.8% of patients were hospitalized, 4.4% were intubated, 29.6% developed pneumonia, and 4.4% had critical illness. The CFR was 9.4%. The risk of hospitalization (odds ratio [OR] = 3.1, 95% confidence interval [CI]: 2.7-3.7), pneumonia (OR = 3.02, 95% CI: 2.6-3.5), ICU admission (OR = 2, 95% CI: 1.5-2.7), and CFR (hazard ratio = 3.5, 95% CI: 2.9-4.2) was higher in patients with three or more comorbidities than in patients with 1, 2, or with no comorbidities. Conclusions: The number of comorbidities may be a determining factor in the clinical course and its outcomes in SARS-CoV-2-positive patients.

Use of coconut water (Cocus nucifera L) for the development of a symbiotic functional drink.

Many studies suggest that probiotic, prebiotic and symbiotic foods may be beneficial in the prevention and management of nutrition and health, the objective of this work was to develop a symbiotic drink based on coconut water. Fermentation was performed using lyophilized Lactobacillus rhamnosus SP1 and inulin as a source of soluble fiber. Different formulations were developed, determining the concentrations of fiber and probiotics. The growth of the probiotic in MRS broth was evaluated, using the plate counting technique in different periods of time. The fermentation time of the drink was 8 h and the shelf life in refrigeration was 14 days evaluated by pH and hedonic scale. The pH of the final drink was 3.48 and the probiotic content was 82 × 10 8 CFU/ml. It is concluded that coconut water can be processed by adding probiotic and prebiotic characteristics with sensory acceptance and adequate preservation characteristics.

Autophagy Inhibition Induces the Secretion of Macrophage Migration Inhibitory Factor (MIF) with Autocrine and Paracrine Effects on the Promotion of Malignancy in Breast Cancer.

Breast cancer is the main cause of cancer-related death in women in the world. Because autophagy is a known survival pathway for cancer cells, its inhibition is currently being explored in clinical trials for treating several types of malignancies. In breast cancer, autophagy has been shown to be necessary for the survival of cancer cells from the triple negative subtype (TNBC), which has the worst prognosis among breast cancers and currently has limited therapeutic options. Autophagy has also been involved in the regulation of protein secretion and, of importance for this work, the inhibition of autophagy is known to promote the secretion of proinflammatory cytokines from distinct cell types. We found that the inhibition of autophagy in TNBC cell lines induced the secretion of the macrophage migration inhibitory factor (MIF), a pro-tumorigenic cytokine involved in breast cancer invasion and immunomodulation. MIF secretion was dependent on an increase in reactive oxygen species (ROS) induced by the inhibition of autophagy. Importantly, MIF secreted from autophagy-deficient cells increased the migration of cells not treated with autophagy inhibitors, indicating that autophagy inhibition in cancer cells promoted malignancy in neighboring cells through the release of secreted factors, and that a combinatorial approach should be evaluated for cancer therapy.

Antioxidant Properties of Amazonian Fruits: A Mini Review of In Vivo and In Vitro Studies.

Brazil, Colombia, Ecuador, Peru, Bolivia, Venezuela, Suriname, Guyana, and French Guiana share an area of 7,295,710 km2 of the Amazon region. It is estimated that the Amazonian forest offers the greatest flora and fauna biodiversity on the planet and on its surface could cohabit 50% of the total existing living species; according to some botanists, it would contain about 16-20% of the species that exist today. This region has native fruit trees in which functional properties are reported as antioxidant and antiproliferative characteristics. Amazon plants offer a great therapeutic potential attributed to the content of bioactive phytochemicals. The aim of this mini review is to examine the state of the art of the main bioactive components of the most studied Amazonian plants. Among the main functional compounds reported were phenolic compounds, unsaturated fatty acids, carotenoids, phytosterols, and tocopherols, with flavonoids and carotenoids being the groups of greatest interest. The main beneficial effect reported has been the antioxidant effect, evaluated in most of the fruits investigated; other reported functional properties were antimicrobial, antimutagenic, antigenotoxic, analgesic, immunomodulatory, anticancer, bronchodilator, antiproliferative, and anti-inflammatory, including hypercholesterolemic effects, leishmanicidal activity, induction of apoptosis, protective action against diabetes, gastroprotective activity, and antidepressant effects.

Prenatal immune challenge induces behavioral deficits, neuronal remodeling, and increases brain nitric oxide and zinc levels in the male rat offspring.

Schizophrenia is a severe mental disorder with numerous etiological susceptibilities. Maternal infection is a key risk factor for schizophrenia. Prenatal lipopolysaccharide (LPS) infection stimulates cytokine production that affects brain development. In the present study, we aimed to investigate the effect of prenatal LPS injection at gestational day (GD) 14-16 on behavioral paradigms, and neuronal morphology in the prefrontal cortex (PFC), basolateral amygdala (BLA), nucleus accumbens (NAcc) and ventral hippocampus (VH) at two critical ages of development: pre-pubertal (postnatal day 35, PD35) and post-pubertal (PD60) age in male rats. We also evaluated the effects of LPS on nitric oxide (NO) and zinc (Zn) levels in seven brain areas (PFC, VH, amygdala, brainstem, striatum and dorsal hippocampus) at PD35 and PD60. LPS induced hyperlocomotion in a novel environment and reduced social contact as well as increased the levels of NO and Zn in the PFC, brainstem and amygdala as observed in other animal models of schizophrenia-related behavior. Furthermore, we found that LPS-treated rats presented post-pubertal neuronal hypertrophy in the PFC and BLA and decreased spine density in the NAcc. The neuronal morphology of neurons in the VH in LPS-treated rats remained unaltered. Interestingly, the anxiogenic-related behavior correlated with neuronal hypertrophy observed in the BLA. Our findings suggest that the behavioral and neural modifications observed in our model could be mediated by the long-lasting alterations in Zn and NO levels in the brain.

Correction to: Hyper-response to Novelty Increases c-Fos Expression in the Hippocampus and Prefrontal Cortex in a Rat Model of Schizophrenia.

The original version of this article unfortunately contained a mistake. The spelling of the author Tommaso Ianniti was incorrect and has been corrected as Tommaso Iannitti. The original article has been corrected.

Autophagy and Its Role in Protein Secretion: Implications for Cancer Therapy.

Autophagy is a protein and organelle degradation pathway important for the maintenance of cytoplasmic homeostasis and for providing nutrients for survival in response to stress conditions. Recently, autophagy has been shown to be important for the secretion of diverse proteins involved in inflammation, intercellular signaling, and cancer progression. The role of autophagy in cancer depends on the stage of tumorigenesis, serving a tumor-suppressor role before transformation and a tumor-survival function once a tumor is established. We review recent evidence demonstrating the complexity of autophagy regulation during cancer, considering the interaction of autophagy with protein secretion pathways. Autophagy manipulation during cancer treatment is likely to affect protein secretion andinter-cellular signaling either to the neighboring cancer cells or to the antitumoral immune response. This will be an important consideration during cancer therapy since several clinical trials are trying to manipulate autophagy in combination with chemotherapy for the treatment of diverse types of cancers.

Hyper-response to Novelty Increases c-Fos Expression in the Hippocampus and Prefrontal Cortex in a Rat Model of Schizophrenia.

Schizophrenia is a debilitating disorder that may have a neurodevelopmental origin. For this reason, animal models based on neonatal insults or manipulations have been extensively used to demonstrate schizophrenia-related behaviors. Among those, the neonatal ventral hippocampus lesion (nVHL) is largely used as a model of schizophrenia-related behavior as it mimics behavioral and neurochemical abnormalities often seen in schizophrenic patients including hyperlocomotion in a novel environment. To investigate the neuroanatomical basis of coding novelty in the nVHL rat, we assessed the behavioral locomotor activity paradigm in a novel environment and measured expression of c-Fos, a marker of neural activation, in brain regions involved in the process of coding novelty or locomotion. Upon reaching adulthood, nVHL rats showed hyperlocomotion in the novel environment paradigm. Moreover, in nVHL rats the expression of c-Fos was greater in the prefrontal cortex (PFC) and CA1 region of the dorsal hippocampus compared to sham rats. Whereas similar expression of c-Fos was observed in the basolateral amygdala, nucleus accumbens and dentate gyrus region of  hippocampus of nVHL and sham rats. These results suggest that the nVHL disrupts the neural activity in the PFC and CA1 region of hippocampus in the process of coding novelty in the rat.

Hepatic mobilization of zinc after an experimental surgery, and its relationship with inflammatory cytokines release, and expression of metallothionein and Zip14 transporter.

OBJECTIVE: To study the relationship between the release of inflammatory cytokines and mobilization of zinc into liver, and the expression of metallothionein and Zip14 transporter after an abdominal surgery in rats. MATERIALS: Thirty-five male Wistar rats were subjected to experimental surgical stress, then the subgroups of five animals were killed at 3, 6, 9, 12, 16, 20 and 24 h. Matched groups without surgery were used as controls. METHODS: Zinc levels were determined by AAS, intracellular zinc by zinquin and dithizone staining. Hepatic metallothionein was assayed by a Cd-saturation method, and IL-1ß, IL-6, and TNF-ß by immunoassays. Zip14 expression was analyzed by real-time RT-PCR, and protein level by immunohistochemistry and Western blot. RESULTS: Experimental surgery produced a hypozincemia, and the increase of hepatic zinc also produced the release of IL-1ß, IL-6 in serum, and the increase of hepatic MT. Histochemistry showed a decrease of free zinc at 3-6 h, but an increase at 9 h (zinquin); meanwhile, total intracellular zinc increased after 9 h (dithizone). RNAm and protein levels of Zip14 were elevated between 6 and 20 h after surgery. CONCLUSION: Biochemical changes described in this work could be part of the APR, and directed to respond to the damage produced during surgical trauma.

Energy Drink Administration in Combination with Alcohol Causes an Inflammatory Response and Oxidative Stress in the Hippocampus and Temporal Cortex of Rats.

Energy drinks (EDs) are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1ß, TNF-α, and iNOS, causing cell death (apoptosis) at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx) and hippocampus (Hp) of adult rats (90 days old). Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1ß, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats.

Chronic cadmium exposure in rats produces pancreatic impairment and insulin resistance in multiple peripheral tissues.

Previous studies have linked cadmium exposure to disturbances in carbohydrate and lipid metabolism. In this study we investigate the effects in Wistar rats of an oral cadmium exposure in drinking water on carbohydrates, lipids and insulin release. Also, using mathematical models we studied the effect of cadmium on insulin resistance and sensitivity in liver, muscle, adipose and cardiovascular tissue. Cadmium exposure induced hyperglycemia, increased insulin release after a glucose load, and caused increases in serum triglycerides, cholesterol, LDL-C and VLDL-C, and a decrease of HDL-C. In addition, there was an accumulation of cadmium in pancreas and an increase of insulin. After exposure, HOMA-IR was increased, while the HOMA-S%, QUICKI and Matsuda-DeFronzo indexes showed decreases. A decrease of insulin sensitivity was shown in muscle and liver. Additionally, cadmium increases insulin resistance in the liver, adipose tissue and cardiovascular system. Finally, ß-cell functioning was evaluated by HOMA-B% index and insulin disposition index, which were decreased, while insulin generation index increased. In conclusion, cadmium increases insulin release, induces hyperglycemia and alters lipid metabolism. These changes likely occur as a consequence of reduced sensitivity and increased insulin resistance in multiple insulin-dependent and non-dependent tissues, producing a biochemical phenotype similar to metabolic syndrome and diabetes.