OBJECTIVE: The 10th leading cause of death in the United States is heart disease. Most of the deaths by heart disease has a correlation with an occlusion of the coronary arteries. While diabetes mellitus is currently the 7th leading cause of death, which is a chronic condition that affects more than 37 million people in America. The global epidemic of obesity largely explains the dramatic increase in the incidence and prevalence of type 2 diabetes (T2D) over the past 25 years. Statins are well known drugs to decrease LDL for individuals who suffer from hypercholesterinemia; however, there is also an increased risk of developing diabetes mellitus. An estimation of 10-20 per 10,000 patients per year demonstrated an excess risk of T2D with the long-term use of statin. Here we examine the effects of simvastatin and pitavastatin on pancreatic ß-cell function to determine whether altered insulin secretion may contribute to an increased risk of T2D. METHODS: The experiments were performed using clonal pancreatic ß-cells (INS-1). The cells were grown in 4 mM glucose in RPMI media. Cells were grown for three days before adding the different types of statins: simvastatin and pitavastatin for one day. Then the cells were used to perform the glucose-induced insulin secretion (GSIS) experiment. Insulin secretion and insulin content were assay using a fluorescence-based immunoassay. The study was calculated using Microsoft Excel. Standard variance and standard error were used to assess the difference sets of data. RESULTS: INS-1 cells responded to acute glucose stimulation after chronic culture in both low (4 mM) and high (11 mM) glucose. Secretion from cells cultured at 4 mM glucose was higher than cells cultured at 11 mM glucose at all glucose concentrations tested, characteristic of the effects of glucolipotoxicity (GLT). Insulin content in cells cultured at high glucose was decreased 8.6-fold compared to cells cultured at the more physiological low glucose condition. When normalized to basal secretion cells cultured at high glucose exhibited basal hypersecretion and increased GSIS compared to those in low glucose. Simvastatin (100 nM, 24 hrs) increased basal insulin secretion to a greater extent than Pitavastatin. The effects of pitavastatin on basal insulin secretion were less consistent than seen with simvastatin. Simvastatin was also shown to inhibit GSIS from cells cultured at 4 mM glucose, while pitavastatin increased GSIS. CONCLUSION: Both pitavastatin and simvastatin alter insulin secretion from pancreatic ß-cells. The effect of simvastatin to both increase basal and decrease GSIS, characteristic of GLT suggests pitavastatin may be the statin of choice to reduce the risk of statin-induced T2D.

A disponibilidade de beta-alanina é o fator limitante para a síntese intramuscular de carnosina. Dessa maneira, aumentar a disponibilidade de beta-alanina para o músculo esquelético é a estratégia mais eficaz para aumentar o conteúdo de carnosina muscular. Postula-se que o transportador de beta-alanina (TauT) possa ser estimulado pela insulina. Para testar essa hipótese, examinamos se a captação de beta-alanina pelo músculo esquelético de humanos é influenciada pela hiperinsulinemia, controlando as concentrações de insulina e beta-alanina no plasma através de infusão intravenosa aguda de beta-alanina. Realizamos um estudo crossover e contrabalanceado em 12 homens jovens e saudáveis (27,5±5,1 anos). Os participantes compareceram ao laboratório em duas ocasiões separadas por 10 semanas de whashout. A beta-alanina foi infundida por via intravenosa em ambos os ensaios por 150 min a uma taxa de 0,11 g.kg.min-1. Em um ensaio, a técnica de clamp euglicêmico hiperinsulinêmico foi usada para obtermos concentrações elevadas de insulina (AI), enquanto que no outro ensaio, foram mantidas concentrações de insulina em jejum (BI). Antes e 30 minutos após a infusão de beta-alanina, amostras de músculo (biópsias percutâneas) foram coletadas para determinar o conteúdo de beta-alanina e carnosina. Coletas sanguíneas foram realizadas antes (0), 10, 30, 60, 90, 120, 150 e 30 min (180) após a infusão para análise de insulina e beta-alanina plasmáticas. Urina 24 h foi coletada após o período de infusão para análise de beta-alanina. Não houve diferenças significantes entre os ensaios na concentração de beta-alanina plasmática (p=0,20), de beta-alanina muscular (p=0,72), de carnosina muscular (p=0,82) e de beta-alanina urinária (p= 0,92). A hiperinsulinemia não aumentou a captação de beta-alanina para o músculo esquelético, nem aumentou a retenção de beta-alanina corporal, pelo menos quando as concentrações de beta-alanina excederam a Vmax do TauT. Nossas descobertas sugerem que as estratégias de suplementação de beta-alanina que manipulam as concentrações de insulina provavelmente apresentam relevância clínica limitada / Beta-alanine availability is limiting for the intramuscular synthesis of carnosine. Thus, increasing beta-alanine availability to skeletal muscle is the most effective strategy to increase muscle carnosine content. It has been postulated that the transmembrane transporter of beta-alanine (TauT) could be stimulated by insulin. To test this hypothesis, we examined whether the beta-alanine uptake by human muscle is influenced by hyperinsulinemia by controlling both insulin and beta-alanine concentrations in plasma via intravenous infusion of beta-alanine. We conducted a counterbalanced crossover study in 12 young men (27.5 ± 5.1 yr). Participants attended to the laboratory on two separated occasions, 10 weeks apart. beta-alanine was intravenously infused on both trials for 150 min at a rate of 0.11 g.kg.min-1. In one trial, a hyperinsulinemic-euglycemic clamp was used to main high insulin concentrations (HI) whereas fasting insulin concentrations (LI) was maintained in the other trial. Before and 30 min after infusion, muscle samples (percutaneous biopsies) were taken to determine beta-alanine and carnosine content. Blood samples were taken before (0), 10, 30, 60, 90, 120, 150 e 30 min (180) after the infusion for plasma insulin and beta-alanine analysis. 24 h urine was colleted after infusion for beta-alanine analysis. No significant differences in plasma beta-alanine (p=0.20), muscle beta-alanine (p=0.72), muscle carnosine (p=0.82) and urinary beta-alanine (p=0.92) were shown between conditions. Hyperinsulinemia did not increase beta-alanine uptake to muscle tissue and bodily tissues, nor did it increase whole-body beta-alanine retention, at least when beta-alanine concentrations exceed the Vmax of TauT. Our findings suggest that beta-alanine supplementation strategies that maniupulate insulin concentrations are probably of limited clinical relevance

INTRODUÇÃO: A infusão aguda de insulina, simulando a resposta insulinêmica a uma refeição rica em carboidratos, promove aumento da atividade nervosa simpática (ANS) e do fluxo sanguíneo (FS) muscular, resultando em aumento da pressão arterial sistólica (PAS) e manutenção da pressão arterial diastólica (PAD) em mulheres pós menopausadas. Nesta população, a execução de uma única sessão de exercício aeróbico promove diminuição da ANS e aumento do FS, reduzindo os níveis de pressão arterial pós-exercício. Entretanto, os efeitos deste exercício sobre as respostas fisiológicas à hiperinsulinemia aguda ainda não foram investigados em mulheres pós menopausadas, que podem ou não estar em uso de terapia estrogênica (TE). OBJETIVO: Avaliar os efeitos agudos do exercício aeróbico prévio sobre a sensibilidade à insulina (SI) e as respostas da PA, ANS, FS muscular e freqüência cardíaca (FC) em condições basais e em resposta à infusão aguda de insulina em mulheres histerectomizadas e pós menopausadas, que estavam em uso ou não de TE. MÉTODOS: 13 mulheres, foram aleatoriamente divididas em 2 grupos: 7 receberam TE (valerato estradiol, 1 mg/dia) e 6 Placebo. Após 6 meses de terapia, os grupos se submeteram a 2 sessões experimentais: exercício físico (cicloergômetro, 45 min, 50%VO2pico) e repouso (60 min sentada). Uma hora após as sessões, a PA (oscilométrica), o FS (pletismografia) e a FC(ECG) foram medidos na posição deitada por 10 min. Em seguida, realizou-se um clampeamento euglicêmico/hiperinsulinêmico (120 min, 100 U/ml) e as variáveis foram medidas no período de equilíbrio. RESULTADOS: A SI foi semelhante nos dois grupos e nas 2 sessões. O uso da TE não afetou as respostas da PA e FC ao exercício e à hiperinsulinemia. Assim, na sessão de repouso, nos 2 grupos, a infusão de insulina aumentou significativamente a PAS (141±4 vs 147±6 mmHg), a PAD (74±3 vs 79±3 mmHg) e a FC (66±3 vs 70±3 bat/min). A execução prévia do exercício diminuiu os valores da PA no período basal e durante a infusão de insulina, além de evitar o aumento da PAD com esta infusão. Além disso, o exercício prévio aumentou a FC basal e fez com que ela não aumentasse com a infusão de insulina. Em relação ao FS, apenas no grupo que recebeu TE, a infusão de insulina aumentou o FS na sessão repouso (2,07±0,24 vs 3,16±0,38 ml.min-1.100ml-1) e, neste grupo, o exercício prévio também tendeu a aumentar o FS basal (2,07± 0,24 vs 2,83± 0,76 ml.min-1.100ml-1,P=0,06). CONCLUSÔES: Em mulheres pos-menopausadas e saudáveis, a execução de uma única sessão de exercício aeróbico reduziu a PA e aumentou a FC, impedindo o efeito da insulina em aumentar a PAD e a FC. Além disso, nas mulheres que faziam uso da TE, uma única sessão de exercício tendeu a promover vasodilatação, e facilitou a vasodilatação induzida pela insulina. Estas respostas ocorreram mesmo na ausência de modificação da SI / INTRODUCTION: Acute insulin infusion, simulating a high carbohydrate lunch, increases sympathetic neural activity (SNA) and blood flow (BF), leading to an increase in systolic blood pressure (SBP) and not changing diastolic blood pressure (DBP) in postmenopausal women. Moreover, in this population, the execution of one exercise bout decrease SNA and increase BF, promoting a decrease in post-exercise blood pressure levels. However, the acute effects of this exercise on physiological responses to hiperinsulinemy were not studied in post-menopausal women, who may be using or not estrogen therapy (ET). OBJECTIVE: To analyze the acute effects of previous aerobic exercise on insulin sensitivity (IS) and the SBP, DBP, ANS, muscle BF and heart rate (HR) measured in baseline under conditions and in response to insulin infusion in postmenopausal histeroctomyzed women, who were receiving ET or not. METHODS: 13 women were randomized into 2 groups: 7 received ET (estradiol valerate, 1mg/dia) and 6 placebo. After 6 months, both groups performed 2 experimental sessions: exercise (cyclergometer, 45 min, 50%VO2peak) and rest (60 min seated). One hour after sessions, blood pressure (oscilometric), BF (pletsmography) and HR (ECG) were measured in the supine position for 10 min. After that, an euglicemic/hiperinsulinemic clamp was performed (120 min, 100 U/ml), and these variables were measured in steady-state period. RESULTS: IS was similar between groups in both sessions. Estrogen therapy did not affect blood pressure and heart rate responses to exercise and to hiperinsulinemia. Therefore, in rest session, in both groups, insulin infusion increased SBP (141±4 vs 147±6 mmHg), DBP (74±3 vs 79±3 mmHg), and HR (66±3 vs 70±3 beats/min). Previous exercise decreased blood pressure levels in baseline condition and during insulin infusion, and attenuated the increase in DBP during infusion. Moreover, previous exercise increased baselçine HR, and attenuated its increase during insulin infusion. BF increased with insulin infusion only in the group who received ET in the rest session (2.07±0.24 vs 3.16±0.38 ml.min-1.100ml-1), and in this group, previous exercise tended to increase baseline BF (2.07± 0.24 vs 2.83± 0.76 ml.min-1.100ml-1,P=0.06). CONCLUSION: In post-menopausal healthy women, one aerobic exercise bout decreased BP and increased HR, attenuating the increase in DBP and HR during insulin infusion. Moreover, in women that were receiving ET, one exercise bout tended to promote vasodilation, and improved the vasodilation induced by insulin. This responses ocurred even with no change in IS

BACKGROUND: Risk factors associated with Metabolic Syndrome (MetS) have been implicated in cardiovascular disease (CVD) development and outcomes. Few studies have investigated relationships between psychological variables, MetS factors, and indices of cardiac structure and function (CSF) among healthy individuals in a single conceptual model. No studies to date have analyzed such relationships in patients with CVD. METHODS: The present study examined associations between cynical hostility (CynHo), MetS factors, and CSF in 186 multi-ethnic post-myocardial infarction (MI) patients. Structural equation modeling was used to test a theory driven model of MetS that had good statistical fit. Primary MetS variables included waist circumference (WC), the homeostatic model of insulin resistance (HOMA-IR), glucose area under the curve (G-AUC), triglycerides (TRIG), high-density lipoprotein cholesterol (HDL-C), and diastolic blood pressures (DBP). Secondary MetS variables included plasminogen activator inhibitor-1 (PAI-1) and a latent inflammation variable comprised of CRP and IL-6. Cardiac function variables were fractional shortening (FS), E/A ratio, and rate-pressure product (RPP). A latent cardiac mass (CM) variable was also created. RESULTS: The final structural model had good model fit (Chi-Square(102)=100.65, p=0.52, CFI=1.00, RMSEA=0.00, and SRMR=0.04). Direct paths were supported between WC and CM and all MetS factors except TRIG and G-AUC. WC was indirectly associated with DBP via CM. The model supported positive direct paths between HOMA-IR and G-AUC, TRIG, and PAI-1, but not inflammation or HDL-C. HOMA-IR demonstrated a direct positive association with RPP and direct inverse associations with FS and E/A ratio. No direct paths were supported between other MetS variables except one between TRIG and HDL-C. CynHo demonstrated a direct positive relationship with HOMA-IR. CONCLUSIONS: Similar to findings in healthy individuals, central adiposity and IR play primary roles in CSF impairment in post-MI patients. Findings suggest that CynHo could promote the progression of metabolic dysfunction and cardiac disease via factors that influence the efficiency of glucose metabolism. Interventions for post-MI patients should take into account both direct and indirect effects of CynHo, central adiposity, and IR on the progression of CVD in this population to reduce adverse outcomes and improve quality of life.

Obesity afflicts more than 30% of the U.S. population and is a major risk factor for the development of hypertension, type II diabetes, and cardiovascular disease. Studies in humans and animals indicate that obesity is associated with increased sympathetic outflow to the vasculature and kidneys. One mechanism postulated to underlie the increase in sympathetic nerve activity (SNA) in obesity is hyperinsulinemia. Little is known regarding the central circuitry underlying elevated SNA and arterial blood pressure (ABP) during hyperinsulinemia and obesity or if sympathoexcitatory circuits are still responsive to insulin in obesity. Hyperinsulinemic-euglycemic clamps elevate SNA to the hind limb vasculature in lean rodents but obesity is associated with resistance to the peripheral and anorexic effects of insulin. Therefore, the first aim was to determine whether diet-induced obesity causes development of insulin resistance in the central circuits mediating SNA. The sympathoexcitatory response to insulin was still intact in diet-induced obese rats indicating a role for insulin in the elevation in SNA and ABP in obesity. The second aim of this project was to identify the specific receptors in the rostral ventrolateral medulla (RVLM) that mediate the elevated SNA during hyperinsulinemia. The RVLM provides basal sympathetic tone and maintains baseline ABP. Glutamate is the major excitatory neurotransmitter and glutamate receptors of the RVLM are known to mediate multiple forms of hypertension. Blockade of RVLM NMDA-specific glutamatergic receptors reverses the increased lumbar SNA associated with hyperinsulinemia. In contrast, blockade of angiotensin II type 1 or melanocortin receptors in the RVLM had no effect on the sympathoexcitatory response to insulin. The goal of the third aim was to identify the cellular mechanisms within RVLM that mediate the elevated SNA and ABP in diet-induced obesity. Blockade of RVLM glutamate receptors reversed the elevated ABP and lumbar SNA associated with diet-induced obesity while it had no effect on rats on a low fat diet or those resistant to weight gain on the high fat diet. Similar to the findings during hyperinsulinemia, blockade of RVLM angiotensin II type 1 or melanocortin receptors had no effect on lumbar SNA or ABP during diet-induced obesity.

A major cause of morbidity and early death in the Western societies is cardiovascular disease (CVD) secondary to atherosclerotic disease. Metabolic aberrations have been linked to CVD. Particular combinations of these so-called risk markers are common and (central) obesity, Type 2 diabetes, impaired glucose tolerance, hypertension, dyslipidemia, dysfibrinolysis and hyperinsulinemia are often associated. This has been entitled the Insulin Resistance Syndrome (1RS), due to underlying insulin resistance. Moreover, aberrations in circulating levels of androgens and IGF-binding proteins are associated with 1RS. The main hypothesis in this thesis was that increased levels of leptin, the recently discovered adipocyte derived hormone in combination with obesity may be an important factor in the link between 1RS and the development of CVD. The association between leptin levels and variables associated with the Insulin Resistance Syndrome was studied in a healthy sample (n=163) of middle-aged men and women from the northern Sweden MONICA health survey. Central obesity was associated with high levels of leptin and insulin in men and women. In contrast, central obesity was linked to low testosterone levels in men, whereas in women, central obesity was associated with high testosterone but low SHBG levels. Furthermore, in males and postmenopausal women central obesity was a major determinant for circulating leptin. Leptin levels were associated with biochemical androgenicity in non-obese men and women. The direction of this association was dependent on gender and body fat distribution. Specifically, testosterone was inversely associated to leptin in non-obese men and in normal weight women whereas testosterone was positively associated to leptin in non-obese women. In contrast, adiposity and insulin levels, but not testosterone, were associated to leptin in obese men and women. Similarly, leptin was associated to IGFBP-1 and proinsulin in non-obese men and premenopausal women. Hyperleptinemia was significantly associated to high PAI-1 levels in men and in centrally obese women. In a multivariate model, high leptin levels predicted PAI-1 levels in men but not in women. Finally, leptin levels were related to blood pressure in obese men. The impact of hyperleptinemia on future risk for development of CVD was tested in a nested case-referent study based on the MONICA and the Västerbotten Intervention Program surveys. It was found that hyperleptinemia and high total cholesterol levels were associated with increased risk for development of myocardial infarction whereas high levels of apolipoprotein A-l were protective. Hyperleptinemia together with hypertension remained as significant risk markers for hemorrhagic stroke whereas hypertension alone predicted ischemic stroke. The combinations of hyperleptinemia on one hand and low apolipoprotein A- 1 and high blood pressure on the other were associated with a pronounced increased risk for myocardial infarction and hemorrhagic stroke, respectively. In conclusion, hyperleptinemia is independently associated with several risk markers for CVD included in the insulin resistance syndrome. Furthermore, high leptin levels predict the development of CVD. / <p>Härtill 5 uppsatser</p> / digitalisering@umu

Central resistance to the actions of insulin and leptin is strongly associated with obesity and type 2 diabetes mellitus (T2DM). These anorexigenic hormones modulate one another’s actions at the neuronal level. To investigate the cellular events underlying the effect of insulin resistance on leptin modulation of hypothalamic neurons, a neuronal cell model was established. The rHypoE-19 cell line expresses the insulin and leptin receptors alongside a complement of signaling molecules rendering it an appropriate model to study the molecular events underlying leptin and insulin crosstalk. Hyperinsulinemia was used to induce insulin resistance and leptin regulation of the rHypoE-19 neurons was analyzed prior to and following the induction of insulin resistance. It was found that the attenuation of insulin signal transduction affects leptin signaling and transcriptional modulation of the rHypoE-19 neurons. These studies will ultimately lend itself to an improved understanding of the complex cellular events that accompany neuronal hormone resistance.

Central resistance to the actions of insulin and leptin is strongly associated with obesity and type 2 diabetes mellitus (T2DM). These anorexigenic hormones modulate one another’s actions at the neuronal level. To investigate the cellular events underlying the effect of insulin resistance on leptin modulation of hypothalamic neurons, a neuronal cell model was established. The rHypoE-19 cell line expresses the insulin and leptin receptors alongside a complement of signaling molecules rendering it an appropriate model to study the molecular events underlying leptin and insulin crosstalk. Hyperinsulinemia was used to induce insulin resistance and leptin regulation of the rHypoE-19 neurons was analyzed prior to and following the induction of insulin resistance. It was found that the attenuation of insulin signal transduction affects leptin signaling and transcriptional modulation of the rHypoE-19 neurons. These studies will ultimately lend itself to an improved understanding of the complex cellular events that accompany neuronal hormone resistance.

INTRODUÇÃO: A infusão aguda de insulina, simulando a resposta insulinêmica a uma refeição rica em carboidratos, promove aumento da atividade nervosa simpática (ANS) e do fluxo sanguíneo (FS) muscular, resultando em aumento da pressão arterial sistólica (PAS) e manutenção da pressão arterial diastólica (PAD) em mulheres pós menopausadas. Nesta população, a execução de uma única sessão de exercício aeróbico promove diminuição da ANS e aumento do FS, reduzindo os níveis de pressão arterial pós-exercício. Entretanto, os efeitos deste exercício sobre as respostas fisiológicas à hiperinsulinemia aguda ainda não foram investigados em mulheres pós menopausadas, que podem ou não estar em uso de terapia estrogênica (TE). OBJETIVO: Avaliar os efeitos agudos do exercício aeróbico prévio sobre a sensibilidade à insulina (SI) e as respostas da PA, ANS, FS muscular e freqüência cardíaca (FC) em condições basais e em resposta à infusão aguda de insulina em mulheres histerectomizadas e pós menopausadas, que estavam em uso ou não de TE. MÉTODOS: 13 mulheres, foram aleatoriamente divididas em 2 grupos: 7 receberam TE (valerato estradiol, 1 mg/dia) e 6 Placebo. Após 6 meses de terapia, os grupos se submeteram a 2 sessões experimentais: exercício físico (cicloergômetro, 45 min, 50%VO2pico) e repouso (60 min sentada). Uma hora após as sessões, a PA (oscilométrica), o FS (pletismografia) e a FC(ECG) foram medidos na posição deitada por 10 min. Em seguida, realizou-se um clampeamento euglicêmico/hiperinsulinêmico (120 min, 100 U/ml) e as variáveis foram medidas no período de equilíbrio. RESULTADOS: A SI foi semelhante nos dois grupos e nas 2 sessões. O uso da TE não afetou as respostas da PA e FC ao exercício e à hiperinsulinemia. Assim, na sessão de repouso, nos 2 grupos, a infusão de insulina aumentou significativamente a PAS (141±4 vs 147±6 mmHg), a PAD (74±3 vs 79±3 mmHg) e a FC (66±3 vs 70±3 bat/min). A execução prévia do exercício diminuiu os valores da PA no período basal e durante a infusão de insulina, além de evitar o aumento da PAD com esta infusão. Além disso, o exercício prévio aumentou a FC basal e fez com que ela não aumentasse com a infusão de insulina. Em relação ao FS, apenas no grupo que recebeu TE, a infusão de insulina aumentou o FS na sessão repouso (2,07±0,24 vs 3,16±0,38 ml.min-1.100ml-1) e, neste grupo, o exercício prévio também tendeu a aumentar o FS basal (2,07± 0,24 vs 2,83± 0,76 ml.min-1.100ml-1,P=0,06). CONCLUSÔES: Em mulheres pos-menopausadas e saudáveis, a execução de uma única sessão de exercício aeróbico reduziu a PA e aumentou a FC, impedindo o efeito da insulina em aumentar a PAD e a FC. Além disso, nas mulheres que faziam uso da TE, uma única sessão de exercício tendeu a promover vasodilatação, e facilitou a vasodilatação induzida pela insulina. Estas respostas ocorreram mesmo na ausência de modificação da SI / INTRODUCTION: Acute insulin infusion, simulating a high carbohydrate lunch, increases sympathetic neural activity (SNA) and blood flow (BF), leading to an increase in systolic blood pressure (SBP) and not changing diastolic blood pressure (DBP) in postmenopausal women. Moreover, in this population, the execution of one exercise bout decrease SNA and increase BF, promoting a decrease in post-exercise blood pressure levels. However, the acute effects of this exercise on physiological responses to hiperinsulinemy were not studied in post-menopausal women, who may be using or not estrogen therapy (ET). OBJECTIVE: To analyze the acute effects of previous aerobic exercise on insulin sensitivity (IS) and the SBP, DBP, ANS, muscle BF and heart rate (HR) measured in baseline under conditions and in response to insulin infusion in postmenopausal histeroctomyzed women, who were receiving ET or not. METHODS: 13 women were randomized into 2 groups: 7 received ET (estradiol valerate, 1mg/dia) and 6 placebo. After 6 months, both groups performed 2 experimental sessions: exercise (cyclergometer, 45 min, 50%VO2peak) and rest (60 min seated). One hour after sessions, blood pressure (oscilometric), BF (pletsmography) and HR (ECG) were measured in the supine position for 10 min. After that, an euglicemic/hiperinsulinemic clamp was performed (120 min, 100 U/ml), and these variables were measured in steady-state period. RESULTS: IS was similar between groups in both sessions. Estrogen therapy did not affect blood pressure and heart rate responses to exercise and to hiperinsulinemia. Therefore, in rest session, in both groups, insulin infusion increased SBP (141±4 vs 147±6 mmHg), DBP (74±3 vs 79±3 mmHg), and HR (66±3 vs 70±3 beats/min). Previous exercise decreased blood pressure levels in baseline condition and during insulin infusion, and attenuated the increase in DBP during infusion. Moreover, previous exercise increased baselçine HR, and attenuated its increase during insulin infusion. BF increased with insulin infusion only in the group who received ET in the rest session (2.07±0.24 vs 3.16±0.38 ml.min-1.100ml-1), and in this group, previous exercise tended to increase baseline BF (2.07± 0.24 vs 2.83± 0.76 ml.min-1.100ml-1,P=0.06). CONCLUSION: In post-menopausal healthy women, one aerobic exercise bout decreased BP and increased HR, attenuating the increase in DBP and HR during insulin infusion. Moreover, in women that were receiving ET, one exercise bout tended to promote vasodilation, and improved the vasodilation induced by insulin. This responses ocurred even with no change in IS

Orientadores: Dora Maria Grassi-Kassisse, Regina Celia Spadari-Bratfisch / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-08T18:16:30Z (GMT). No. of bitstreams: 1 Miotto_AlexandreMarcucci_D.pdf: 1787456 bytes, checksum: dd0dd1fd4def2c09dbdbcec80f8f9888 (MD5) Previous issue date: 2006 / Resumo: Diversas doenças como dislipidemia, hiperinsulinemia associada a diabetes tipo 2, hipertensão, aterosclerose e outras doenças cardiovasculares são decorrentes do estilo de vida moderno, principalmente aquele verificado nos ricos países ocidentais. Estas desordens, antes prevalentes nas pessoas mais idosas, estão se tornando atualmente epidêmicas e afetando pessoas de todas as idades. A dieta desbalanceada é, certamente, um dos maiores contribuidores para estas anormalidades. Neste estudo nós alimentamos ratos com uma dieta hiperlípidica por 6 semanas para indução de um estado de hiperlipidemia, com elevação das concentrações plasmáticas de colesterol total, do LDL-colesterol e dos triglicerídeos, além de apresentar também significativo aumento do índice aterogênico. Os resultados mostraram também um desenvolvimento paralelo de hiperinsulinemia (0,75±0,02 vs 1,30 vs 0,12 ng/mL; N vs H) com níveis glicêmicos elevados nos ratos alimentados com dieta hiperlipídica e após jejum overnight (72,6±3 vs 84,1±1,5 mg/dL; N vs H), além de suave hipertensão e hipertrofia ventricular cardíaca. Nós concluímos que estas alterações metabólicas e cardiovasculares foram iniciadas pela dieta hiperlipídica administrada aos ratos, que esta condição se estabeleceu de forma relativamente rápida e que se encontra ainda em estágio inicial, podendo caracterizar o início da Síndrome Plurimetabólica, também conhecida como Síndrome X / Abstract: Several diseases, such as dyslipidemia, hyperinsulinemia and type 2 diabetes mellitus, hypertension, atherosclerosis, cardiovascular diseases, seem to be decurrent of the modern life style, mainly verified in the rich occidental countries. These disorders incidence, before prevalent in the elderly are more and more frequent and became nowepidemic by affecting people of all ages. The disbalanced diet is a greater contributor for these abnormalities. In this study we fed rats with a high fat-cholesterol diet for six weeks to induce a hyperlipidaemia, which showed enhanced levels of total cholesterol, LDLcholesterol and triglycerides, beyond presentate also a significative increase in the atherogenic index. The results showed also a parallel development of hyperinsulinemia (0.75±0.02 vs 1.30 vs 0.12 ng/mL; N vs H) with glicemic levels elevated in rats fed with hyperlipidemic diet and after overnight fast (72.6±3 vs 84.1±1.5 mg/dL; N vs H), beyond mild hypertension and ventricular cardiac hypertrophy after diet administration. We conclude that there was hazardous metabolic and cardiovascular alterations and all of them were triggered by the high fat-cholesterol diet administered to the rats in a very short time, which may characterize the beggining of Plurimetabolic Syndrome or Syndrome X / Doutorado / Fisiologia / Mestre em Biologia Funcional e Molecular