Insulin signal decrease in muscle but not in the liver of castrated male rats from chronic exposure to fluoride

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alterações vasculares em ratos obesos por dieta rica em gordura: papel da Via L-arginina/NO Endotelial

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acute exercise reverses aged-induced impairments in insulin signaling in rodent skeletal muscle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphofunctional Alterations in Endocrine Pancreas of Short- and Long-term Dexamethasone-treated Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reduction of insulin signalling pathway IRS-1/IRS-2/AKT/mTOR and decrease of epithelial cell proliferation in the prostate of glucocorticoid-treated rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Glucose Tolerance and Insulin Action in Monosodium Glutamate (MSG) Obese Exercise-trained Rats

The present study was designed to evaluate the effects of chronic aerobic exercise (swimming, 1h/day, 5 days/week, with an overload of 5% body weight) on glucose metabolism in obese male Wistar rats. Hypothalamic obesity was induced through administration of monosodium glutamate (MSG) at 4 mg/g of body weight every other day from birth to 14 days old. Fourteen weeks after drug administration, the rats were separated into two groups: MSG-S (sedentary) and MSG-T (swimming for 10 weeks). Rats of the same age and strain, receiving saline in place of MSG, were used as control (C), and subdivided into two groups: C-S and C-T. At the end of the experimental period, an oral glucose tolerance test was performed and serum glucose (AG) and insulin (AI) were evaluated. A constant for serum glucose decrease (Kitt) in response to exogenous insulin was calculated. Soleus muscle strips and adipose tissue samples were incubated and insulin stimulated glucose uptake determined. No differences were observed in AG among the 4 groups. MSG-S rats showed higher AI (418%) and lower Kitt (92.3%) than C-S rats. T-rats showed higher glucose uptake by muscle (224.0%) and adipose tissues (94.1%) than S-rats. Among trained rats, glucose uptake by muscle was higher in MSG-T (5.4%) than in C-T. while the opposite was observed in adipose tissue (39% higher in C-T). Chronic aerobic exercise was able to improve glucose tolerance and reduce insulin resistance in MSG-obese rats. These effects were associated to an increase in glucose uptake by muscle and adipose tissue in response to insulin.

Low ethanol consumption induces enhancement of insulin sensitivity in liver of normal rats

Moderate amounts of alcohol intake have been reported to have a protective effect on the cardiovascular system and this may involve enhanced insulin sensitivity. We established an animal model of increased insulin sensitivity by low ethanol consumption and here we investigated metabolic parameters and molecular mechanisms potentially involved in this phenomenon. For that, Wistar rats have received drinking water either without (control) or with 3% ethanol for four weeks. The effect of ethanol intake on insulin sensitivity was analyzed by insulin resistance index (HOMA-IR), intravenous insulin tolerance test (IVITT) and lipid profile. The role of liver was investigated by the analysis of insulin signaling pathway, GLUT2 gene expression and tissue glycogen content. Rats consuming 3% ethanol showed lower values of HOMA-IR and plasma free fatty acids (FFA) levels and higher hepatic glycogen content and glucose disappearance constant during the IVITT. Neither the phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), nor its association with phosphatidylinositol-3-kinase (PI3-kinase), was affected by ethanol. However, ethanol consumption enhanced liver IRS-2 and protein kinase B (Akt) phosphorylation (3 times, P < 0.05), which can be involved in the 2-fold increased (P < 0.05) hepatic glycogen content. The GLUT2 protein content was unchanged. Our findings point out that liver plays a role in enhanced insulin sensitivity induced by low ethanol consumption. © 2005 Elsevier Inc. All rights reserved.

Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. © 2013 Moura et al; licensee BioMed Central Ltd.

Maternal periodontal disease in rats decreases insulin sensitivity and insulin signaling in adult offspring

Background: Periodontal disease during pregnancy has been recognized as one of the causes of preterm and lowbirth- weight (PLBW) babies. Several studies have demonstrated that PLBW babies are prone to developing insulin resistance as adults. Although there is controversy over the association between periodontal disease and PLBW, the phenomenon known as programming can translate any stimulus or aggression experienced during intrauterine growth into physiologic and metabolic alterations in adulthood. The purpose of the present study is to investigate whether the offspring of rats with periodontal disease develop insulin resistance in adulthood. Methods: Ten female Wistar rats were divided into periodontal disease (PED) and control (CN) groups. All rats were mated at 7 days after induction of periodontal disease. Male offspring were divided into two groups: 1) periodontal disease offspring (PEDO; n = 24); and 2) control offspring (CNO; n = 24). Offspring body weight was measured from birth until 75 days. When the offspring reached 75 days old, the following parameters were measured: 1) plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and tumor necrosis factor-α (TNF-α); 2) insulin sensitivity (IS); and 3) insulin signal transduction (IST) in insulin-sensitive tissues. Results: Low birth weight was not detected in the PEDO group. However, plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and TNF-α were increased and IS and IST were reduced (P <0.05) in the PEDO group compared with the CNO group. Conclusion: Maternal periodontal disease may induce insulin resistance and reduce IST in adult offspring, but such alterations are not attributable to low birth weight.

Induction of the 72 kDa heat shock protein by glucose ingestion in black pregnant women

Obese Black women are at increased risk for development of gestational diabetes mellitus and have worse perinatal outcomes than do obese women of other ethnicities. Since hsp72 has been associated with the regulation of obesity-induced insulin resistance, we evaluated associations between glucose ingestion, hsp72 release and insulin production in Black pregnant women. Specifically, the effect of a 50-g glucose challenge test (GCT) on heat shock protein and insulin levels in the circulation 1 h later was evaluated. Hsp27 and hsp60 levels remained unchanged. In contrast, serum levels of hsp72 markedly increased after glucose ingestion (p = 0.0054). Further analysis revealed that this increase was limited to women who were not obese (body mass index <30). Insulin levels pre-GCT were positively correlated with body mass index (p = 0.0189). Median insulin concentrations also increased post GCT in non-obese women but remained almost unchanged in obese women. Post-GCT serum hsp72 concentrations were inversely correlated with post GCT insulin concentrations (p = 0.0111). These observations suggest that glucose intake during gestation in Black women rapidly leads to an elevation in circulating hsp72 only in non-obese Black women. The release of hsp72 may regulate the extent of insulin production in response to a glucose challenge and, thereby, protect the mother and/or fetus from development of hyperglycemia, hyperinsulinemia, and/or immune system alterations. © 2013 Cell Stress Society International.

Intra-abdominal fat is related to metabolic syndrome and non-alcoholic fat liver disease in obese youth

Background: Previous studies have shown an association between adiposity, especially intra-abdominal adipose tissue, and hemodynamic/metabolic comorbidities in adults, however it is not clear in pediatric population. The aim of the study was to analyze the relationship between non-alcoholic fatty liver disease (NAFLD) and components of metabolic syndrome (MS) with values of intra-abdominal (IAAT) and subcutaneous (SCAT) adipose tissue in obese children and adolescents.Methods: Cross-sectional study. Subjects: 182 obese sedentary children and adolescents (aged 6 to 16 y), identified by the body mass index (BMI). Measurements: Body composition and trunk fat by dual-energy X-ray absorptiometry- DXA; lipid profile, blood pressure and pubertal stage were also assessed. NAFLD was classified as absent (0), mild (1), moderate (2) and severe (3), and intra-abdominal and subcutaneous abdominal fat thickness were identified by ultrasound. The MS was identified according to the cut offs proposed by World Health Organization adapted for children and adolescents. The chi-square test was used to compare categorical variables, and the binary logistic regression indicated the magnitude of the associations adjusted by potential cofounders (sex, age, maturation, NAFLD and HOMA-IR).Results: Higher quartile of SCAT was associated with elevated blood pressure (p = 0.015), but not associated with NAFLD (p = 0.665). Higher IAAT was positively associated with increased dyslipidemia (p = 0.001), MS (p = 0.013) and NAFLD (p = 0.005). Intermediate (p = 0.007) and highest (p = 0.001) quartile of IAAT were also associated with dyslipidemia, independently of age, sex, maturation, NAFLD and HOMA-IR (homeostatic model assessment-insulin resistance).Conclusion: Obese children and adolescents, with higher IAAT are more prone to develop MS and NAFLD than those with higher values of SCAT, independent of possible confounding variables. © 2013 Silveira et al.; licensee BioMed Central Ltd.

Comparação entre o volume renal em fetos de gestantes hiperglicêmicas e o volume renal em fetos de gestantes normoglicêmicas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Indicadores de síndrome metabólica em meninas púberes

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Influência do tempo de exposição à obesidade sobre a expressão gênica e protéica do sistema regulador do trânsito de cálcio miocárdico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)