Effects of chronic stress and high-fat diet on metabolic and nutritional parameters in Wistar rats / Efeitos do estresse crônico e da dieta rica em gordura sobre os parâmetros metabólicos e nutricionais em ratos Wistar

OBJECTIVE: The aim of this study was assess the role of chronic stress on the metabolic and nutritional profile of rats exposed to a high-fat diet. MATERIALS AND METHODS: Thirty-day-old male Wistar rats (70-100 g) were distributed into four groups: normal-diet (NC), chronic stress (St), high-fat diet (HD), and chronic stress/high-fat diet (HD/St). Stress consisted at immobilization during 15 weeks, 5 times per week, 1h per day; and exposure to the high-fat diet lasted 15 weeks. Nutritional and metabolic parameters were assessed. The level of significance was 5%. RESULTS: The HD group had final body weight, total fat, as well as insulin and leptin increased, and they were insulin resistant. The St and HD/St had arterial hypertension and increased levels of corticosterone. Stress blocked the effects of the high-fat diet. CONCLUSION: Chronic stress prevented the appearance of obesity. Our results help to clarify the mechanisms involved in metabolic and nutritional dysfunction, and contribute to clinical cases linked to stress and high-fat diet.

OBJETIVO: Avaliar o papel do estresse crônico sobre parâmetros metabólicos e nutricionais de ratos expostos à dieta rica em gordura. MATERIAIS E MÉTODOS: Ratos Wistar machos (30 dias de idade/70-100 g) foram distribuídos em quatro grupos: dieta-normal (NC), estresse crônico (St), dieta rica em gordura (HD) e estresse crônico/dieta rica em gordura (HD/St). O estresse consistiu em imobilização durante 15 semanas, 5 vezes por semana 1h por dia e a dieta rica em gordura foi oferecida por 15 semanas. Parâmetros nutricionais e metabólicos foram avaliados. O nível de significância foi de 5%. RESULTADOS: HD tiveram peso corpóreo, gordura total e níveis de insulina e leptina aumentados e foram resistentes à insulina. Os grupos St e HD/St manifestaram hipertensão e níveis séricos de corticosterona elevados. O estresse bloqueou os efeitos da dieta. CONCLUSÃO: O estresse impediu o surgimento dela. Nossos resultados ajudam compreender os mecanismos envolvidos na disfunção metabólica e nutricional e contribuem para casos clínicos de estresse e dietas ricas em gorduras.

Effect of pitavastatin in different SLCO1B1 backgrounds on repaglinide pharmacokinetics and pharmacodynamics in healthy Chinese males

The effect of pitavastatin and SLCO1B1 genetic background on the pharmacokinetic and pharmacodynamic properties of repaglinide was investigated. In this randomized, placebo-controlled, crossover study, twelve healthy Chinese males were administered with pitavastatin 4 mg/d or the placebo for 5 d followed by repaglinide 4 mg given orally on d 5. Plasma repaglinide and glucose levels were measured by liquid chromatography-tandem mass spectrometry [LC/MS/MS] and the glucose oxidase method, respectively. Treatment with pitavastatin significantly increased the peak plasma concentration [C[max]] of repaglinide [P=0.003] in SLCO1B1[asterisk]1b homozygotes [P=0.015] and SLCO1B1[asterisk]15 carriers [P=0.031]. Treatment with pitavastatin led to a marginal increase in the area under plasma concentration-time curve from 0 h to infinity [AUC[0][rightwards arrow][infinity]] of repaglinide [P=0.091]. There was no significant difference in pharmacokinetic parameters or hypoglycemic effects of repaglinide among SLCO1B1 genotypes in either the pitavastatin or control group. Pitavastatin increased the C[max] of the plasma concentration of repaglinide in an SLCO1B1 genotype dependent manner, but had no apparent effect on the pharmacodynamics of repaglinide in healthy volunteers. The p values for this statement were not reported

Estudo comparativo da biodisponibilidade relativa de duas formulações de glimepirida em voluntários sadios de ambos os sexos após administração de uma dose única de um comprimido de 4 mg / Comparison study of two glimepiride formulations bioavailability in healthy volunteers of both sexes after a single dose administration

OBJETIVO: Comparar a biodisponibilidade de duas formulações de glimepirida em 26 voluntários sadios de ambos os sexos. MATERIAL E MÉTODOS: O estudo foi aberto, cruzado e randomizado com dois períodos e wash out de 14 dias. As amostras foram obtidas em um intervalo de 48 horas. As concentrações de glimepirida foram analisadas por HPLC MS/MS. Das curvas de concentração de glimepirida no plasma versus tempo, foram obtidos os seguintes parâmetros farmacocinéticos: ASC(0-t), ASC(0-∞), Cmax, Ke, Tmax e T1/2. RESULTADOS: A razão entre as média geométricas de Glimepirida/Amaryl® 4 mg foi de 102,35 por cento para ASC(0-t); 102,35 por cento para ASC(0-∞) e 99,31 por cento para Cmax. Os intervalos de confiança de 90 por cento (IC 90 por cento) foram de 92,62-109,55 por cento; 95,62-109,55 por cento e 88,60-111,32 por cento, respectivamente. CONCLUSÃO: Como o IC 90 por cento para Cmax, ASC(0-t) e ASC(0-∞) estava dentro do intervalo de 80-125 por cento, concluiu-se que ambas as formulações foram bioequivalentes de acordo com o grau e a extensão de sua absorção.

OBJECTIVE: To compare the bioavailability of two glimepiride 4-mg tablet formulation in 26 healthy volunteers of both sexes. MATERIAL AND METHODS: The study was conducted open with randomized two-period crossover design and a 14-day washout period. Samples were obtained over a 48-hour interval. Glimepiride concentrations were analyzed by LC-MS-MS. From the glimepiride plasma concentration versus time curves the following pharmacokinetic parameters were obtained: AUC(0-last), AUC(0-t), AUC(0-∞), Ke, T1/2, Cmax, and Tmax. RESULTS: Geometric mean of Glimepirida/Amaryl® 4 mg was 102.35 percent for AUC(0-t), 102.35 percent for AUC(0-∞) and 99.31 percent for Cmax. The 90 percent CI was 92.62-109.55 percent; 95.62-109.55 percent e 88.60-111.32 percent, respectively. CONCLUSION: Since the 90 percent CI for both Cmax, AUC(0-t), and AUC(0-∞) were within the interval of 80-125 percent, it was concluded that both formulations were bioequivalent, according to both the rate and extent of absorption.

Terapia de reposiçäo hormonal contínua na pós-menopausa: ênfase no hormônio do crescimento, insulina, fator de crescimento semelhante à insulina I (IGF-I)e proteína ligadora 3 do IGF (IGFBP-3) / Continuous hormonal replacement therapy in post-menopause: emphasisin growth hormone, insulin, I insulin-like growth factors (IGF-I) and 3 binding protein of IGF (IGFBP-3)

A importância da terapia de reposiçäo hormonal da menopausa (TRHM) na qualidade de vida na pós-menopausa é inquestionável. Entretanto, nem todos os efeitos determinados pelo seu emprego estäo bem estabelecidos. Este estudo tem como objetivo avaliar a influência da TRHM sobre os níveis séricos do hormónio do crescimento (GH), fator de crescimento semelhante à insulina I (IGF-I), proteína ligadora 3 do IGF (IGFBP-3), glicose e insulina. Realizamos um ensaio clínico controlado, prospectivo, longitudinal e comparativo, no qual 53 mulheres na pós-menopausa, natural ou cirúrgica, foram submetidas ou näo a TRHM contínua, durante um período de 6 meses, com estrogênios conjugados (EC-0,625mg/d) associados ou näo ao acetato de medroxiprogesterona (AMP-2,5mg/d), pela via oral. As participantes foram subdivididas em 3 grupos: Grupo EC + AMP > 20 mulheres com útero, que utilizaram EC e AMP; Grupo EC > 20 mulheres histerectomizadas, que usaram EC; Grupo C > 13 mulheres, sem TRHM. Ao início e ao final do estudo foram realizadas as dosagens basais do GH; IGF-I e IGFBP-3. Também realizamos o teste oral de tolerância à glicose (TOTG) de 2 horas, com determinaçäo dos níveis de glicose e insulina; a área abaixo da curva (AAC) de glicose e de insulina e o índice de resistência à insulina (IRI). O emprego da TRHM reduziu os níveis do IGF-I no EC + AMP (p= 0,01) e EC (p= 0,0007), sem alteraçäo nos níveis do IGFBP-3. Os níveis do GH se elevaram mediante a TRHM, (EC + AMP: p= 0,004 e EC: p= 0,0003), entretanto, as concentraçöes séricas do IGF-I e do IGFBP-3 näo parecem ser bons marcadores da secreçäo circadiana do GH. Aos 6 meses observou-se uma correlaçäo negativa do IGF-I com a AAC de glicose nos três grupos (EC + AMP: r= -0,42, p= 0,06; EC: r= -0,58, p= 0,007 e C: r= -0,64, p= 0,01). O IGFBP-3 e a AAC de glicose apresentaram correlaçäo negativa no grupo EC (r= -0,45, p= 0,04) e tendência no EC + AMP (r= -0,42, p= 0,06). A associaçäo do AMP determinou o aparecimento de ITG em 30 por cento das pacientes do grupo EC + AMP (n= 6). Nossos dados sugerem uma interaçäo entre o metabolismo dos carboidratos com o IGF-I e o IGFBP-3. Os efeitos gerados pelo emprego prolongado da TRHM contínua na regulaçäo do GH, IGF-I e IGFBP-3 ainda necessitam elucidaçäo.

Regulation of leptin gene expression by insulin and growth hormone in mouse adipocytes

The role of leptin in the control of obesity, insulin resistance and type II diabetes has been reported, however, the regulatory mechanism of leptin in animals affected by hormones is not clearly understood. In this study, the effects of insulin, epinephrine, growth hormone or dexamethasone on the expression of leptin was examined in mouse primary adipocytes. The leptin expression was also studied in the adipose tissue of the mouse treated with insulin or growth hormone (0.3 or 0.6 units/animal). Insulin (100 nM) or dexamethasone (100 nM) stimulated leptin mRNA transcription while epinephrine (100 nM) alleviated its transcription in mouse primary adipocytes. The level of leptin protein in cultured media of adipocytes treated with insulin or dexamethasone was higher than that of the control group but growth hormone or epinephrine treatment had no effect on them. Insulin administration (0.6 units/mouse) enhanced leptin mRNA as well as leptin protein in mouse adipose tissue but growth hormone administration (0.3 or 0.6 units/mouse) had no effect on them. Leptin protein level in sera of mice injected with insulin or growth hormone was not significantly different from that of control group. These results indicate that both insulin and dexamethasone stimulate leptin gene expression and secretion of its product, whereas, growth hormone has no effect on the expression of leptin gene in mouse adipocytes.

Regulation of leptin gene expression by insulin and growth hormone in mouse adipocytes

The role of leptin in the control of obesity, insulin resistance and type II diabetes has been reported, however, the regulatory mechanism of leptin in animals affected by hormones is not clearly understood. In this study, the effects of insulin, epinephrine, growth hormone or dexamethasone on the expression of leptin was examined in mouse primary adipocytes. The leptin expression was also studied in the adipose tissue of the mouse treated with insulin or growth hormone (0.3 or 0.6 units/animal). Insulin (100 nM) or dexamethasone (100 nM) stimulated leptin mRNA transcription while epinephrine (100 nM) alleviated its transcription in mouse primary adipocytes. The level of leptin protein in cultured media of adipocytes treated with insulin or dexamethasone was higher than that of the control group but growth hormone or epinephrine treatment had no effect on them. Insulin administration (0.6 units/mouse) enhanced leptin mRNA as well as leptin protein in mouse adipose tissue but growth hormone administration (0.3 or 0.6 units/mouse) had no effect on them. Leptin protein level in sera of mice injected with insulin or growth hormone was not significantly different from that of control group. These results indicate that both insulin and dexamethasone stimulate leptin gene expression and secretion of its product, whereas, growth hormone has no effect on the expression of leptin gene in mouse adipocytes.