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1.
Mediators Inflamm ; 2019: 1491083, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30983877

RESUMO

Aim: The development of type 2 diabetes (T2DM) is associated with disturbances of immune status that may be reflected by alterations of the profile of circulating immune cells. In order to study whether there exists genetic predisposition to these alterations, we investigated the relative content of circulating monocyte and lymphocyte subpopulations at fasting condition and upon stimulation by short-term hyperinsulinemia in nondiabetic first-degree relatives (FDR) of T2DM patients and in control subjects. Materials and Methods: 19 nondiabetic (FDR) and 19 control subjects without a family history of diabetes (all men) matched for age and BMI underwent 2-hour hyperinsulinemic-euglycemic clamp. Blood samples taken before and at the end of the clamp were used for the flow cytometry analysis of lymphocyte and monocyte populations and for the assessment of cytokine levels. Results: At fasting conditions, FDR showed a higher CD4/CD8 ratio of peripheral lymphocytes, a higher percentage of Th17 lymphocytes, and a lower content of intermediate monocytes when compared to controls. The CD4/CD8 ratio correlated with fat mass, insulin, and HOMA-IR in the entire group of subjects. Hyperinsulinemia decreased a relative content of peripheral CD4+ and increased a relative content of CD8+ T lymphocytes, thus decreasing the CD4/CD8 ratio by 18-22% in both groups of subjects. In FDR but not in controls, the decrease of CD4+ T lymphocyte content was partially based on the decrease of TH2 and TH17 lymphocyte subpopulations. In control subjects but not in FDR, the number of intermediate monocytes has declined in response to hyperinsulinemia. Conclusion: The alterations of the CD4/CD8 lymphocyte ratio, relative content of TH17 cells, and intermediate monocytes in FDR are features of genetic predisposition to T2DM and may play a role in pathogenesis of T2DM. Short-term hyperinsulinemia affected mostly the immune cell populations deregulated in FDR subjects, which suggests important interplay between immune system homeostasis and insulin levels.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Jejum/sangue , Hiperinsulinismo/sangue , Subpopulações de Linfócitos/metabolismo , Monócitos/metabolismo , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Relação CD4-CD8 , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Resistência à Insulina/fisiologia , Masculino , Células Th17/metabolismo , Células Th2/metabolismo
2.
Diab Vasc Dis Res ; 16(2): 171-177, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31014095

RESUMO

BACKGROUND: Despite optimal treatment, type II diabetes mellitus remains associated with an increased risk for future cardiovascular events. We sought to determine the association between baseline fasting plasma insulin levels and major adverse cardiovascular outcomes in patients with type II diabetes mellitus and high-risk vascular disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial. METHODS: We included all patients with type II diabetes mellitus who had a central laboratory measured fasting plasma insulin level drawn at baseline as part of the study protocol. Hazard ratios were generated for the risk of major adverse cardiovascular outcomes (composite of cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina and coronary revascularization) with increasing quartile of baseline fasting plasma insulin level. We then performed a multivariable regression adjusting for significant baseline characteristics. RESULTS: Among 12,092 patients in ACCELERATE, 2042 patients with type II diabetes mellitus had a baseline fasting plasma insulin level drawn. Median follow-up was 28 months. The study population had a mean age of 66.6 years, 79.2% male and 96.2% had established coronary artery disease. During follow-up, major adverse cardiovascular outcomes occurred in 238 patients (11.6%); of these events, 177 were coronary revascularization (8.7%). We observed a statistically significant relationship between rates of revascularization and rising quartile of baseline fasting plasma insulin level which was not noted for the other individual components of major adverse cardiovascular outcomes. Patients with type II diabetes mellitus who underwent revascularization were noted to have significantly higher baseline fasting plasma insulin levels (27.7 vs 21.4 mU/L, p-value = 0.009) although baseline haemoglobin A1c (6.63% vs 6.55%), body mass index (31.5 vs 31.1 kg/m2) and medical therapy were otherwise similar to the group not undergoing revascularization. Following multivariable regression adjusting for significant characteristics including exposure to evacetrapib, the log of baseline fasting plasma insulin level was found to be an independent predictor for major adverse cardiovascular outcomes (hazard ratio = 1.36, 95% confidence interval = 1.09-1.69, p-value = 0.007); this was driven by need for future revascularization (hazard ratio = 1.56, 95% confidence interval = 1.21-2.00, p-value = 0.001). CONCLUSION: In a contemporary population of patients with type II diabetes mellitus and high-risk vascular disease on optimum medical therapy, baseline hyperinsulinaemia was an independent predictor for major adverse cardiovascular outcomes and need of future coronary revascularization. These results suggest a pathophysiological link between hyperinsulinaemia and progression of atherosclerotic vascular disease among diabetics.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/sangue , Jejum/sangue , Hiperinsulinismo/sangue , Insulina/sangue , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/terapia , Feminino , Humanos , Hiperinsulinismo/complicações , Hiperinsulinismo/mortalidade , Hiperinsulinismo/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo
3.
Acta Diabetol ; 56(7): 785-795, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30859314

RESUMO

AIMS: Circulating endothelial progenitor cells (EPCs) play a key role in maintaining endothelial function. Dysfunction of EPCs is associated with the cardiovascular complication of diabetes. The purpose of this study is to investigate the direct effects of hyperinsulinemia on EPCs and the underlying mechanisms. METHODS: EPCs isolated from healthy adults were cultured with various concentrations of insulin (control group, without insulin; physiological insulin group, 10 nM insulin and hyperinsulinemia group, 100 nM insulin) with or without phosphatidylinositol-3-kinase (PI3-K) inhibitor (LY294002, 5 µM), endothelial nitric oxide synthase (eNOS) inhibitor (L-NG-nitro-arginine methyl ester (L-NAME), 100 µM), sodium nitroprusside (SNP, 25 µM), p38 mitogen-activated protein kinase(MAPK) inhibitor (SB203580, 5 µM) or extracellular signal-regulated kinases (ERK) 1/2 inhibitor (PD98059, 10 µM). Proliferation, tube formation, and apoptosis of EPCs were determined. Expressions of eNOS, PI3-K, protein kinase B (Akt), p38 MAPK, and ERK 1/2 were assessed. RESULTS: Hyperinsulinemia caused a significant decrease in proliferation and tube formation abilities than control group. Hyperinsulinemia increased apoptosis rate of EPCs than control group. Furthermore, hyperinsulinemia downregulated phosphorylation of eNOS, PI3-K and Akt, and upregulated phosphorylation of p38 MAPK and ERK. SNP could restore impaired tube formation induced by hyperinsulinemia. P38 MAPK inhibitor but not ERK inhibitor could decrease apoptosis induced by hyperinsulinemia. CONCLUSION: Hyperinsulinemia impaired EPCs' tube formation ability by downregulation of PI-3K/Akt/eNOS pathway. Hyperinsulinemia induced apoptosis of EPCs via upregulation of p38 MAPK.


Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/fisiologia , Hiperinsulinismo/fisiopatologia , Insulina/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Adulto , Animais , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Progenitoras Endoteliais/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/patologia , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Transdução de Sinais/efeitos dos fármacos
4.
Nat Commun ; 10(1): 1060, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837465

RESUMO

Circulating levels of glycine have previously been associated with lower incidence of coronary heart disease (CHD) and type 2 diabetes (T2D) but it remains uncertain if glycine plays an aetiological role. We present a meta-analysis of genome-wide association studies for glycine in 80,003 participants and investigate the causality and potential mechanisms of the association between glycine and cardio-metabolic diseases using genetic approaches. We identify 27 genetic loci, of which 22 have not previously been reported for glycine. We show that glycine is genetically associated with lower CHD risk and find that this may be partly driven by blood pressure. Evidence for a genetic association of glycine with T2D is weaker, but we find a strong inverse genetic effect of hyperinsulinaemia on glycine. Our findings strengthen evidence for a protective effect of glycine on CHD and show that the glycine-T2D association may be driven by a glycine-lowering effect of insulin resistance.


Assuntos
Doença das Coronárias/genética , Diabetes Mellitus Tipo 2/genética , Glicina/sangue , Hiperinsulinismo/genética , Redes e Vias Metabólicas/genética , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Glicina/metabolismo , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/epidemiologia , Incidência , Polimorfismo de Nucleotídeo Único
5.
BMC Vet Res ; 15(1): 65, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808423

RESUMO

BACKGROUND: A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 µIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated to receive either velagliflozin (0.3 mg/kg BW orally once daily, n = 12), or a placebo (n = 10-12) for 16 wk. The subjects were fed 7.5 g NSC/kg BW/day to maintain a fat body condition. Safety was assessed through daily monitoring, veterinary examination, and the measurement of fasting blood glucose, biochemistry and haematology. Efficacy at reducing post-prandial hyperinsulinemia was assessed using a diet challenge every 8 wk. during treatment and 4 wk. after withdrawal. RESULTS: Velagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin Cmax) did not change significantly in the control animals over the entire study period (P = 0.101). In contrast, insulin Cmax (mean ± SE) concentrations fell over time in the velagliflozin-treated group from 205 ± 25 µIU/mL in wk. 0, to 119 ± 19 µIU/mL (P = 0.015) and 117 ± 15 µIU/ml (P = 0.029) after 8 and 16 wk. of treatment, respectively. Although the insulin Cmax in this group was not significantly lower than in controls at wk-8 (P = 0.061), it was lower at wk-16 (P = 0.003), and all 12 treated ponies were below the previously-determined risk threshold for laminitis at this time. After 4 wk. withdrawal, the insulin Cmax returned to 199 ± 36 µIU/mL in the treated group, with no rebound effect. CONCLUSIONS: Velagliflozin appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them.


Assuntos
Doenças dos Cavalos/tratamento farmacológico , Hiperinsulinismo/veterinária , Nitrilos/uso terapêutico , Animais , Doenças dos Cavalos/sangue , Cavalos , Hiperinsulinismo/sangue , Hiperinsulinismo/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Distribuição Aleatória , Resultado do Tratamento
6.
Diabetes Metab Syndr ; 13(1): 382-388, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641729

RESUMO

AIM: To evaluate the association between high triglyceride/HDL-cholesterol (TG/HDL-C) ratio and insulin resistance (IR) or hyperinsulinemia after oral glucose tolerance test (OGTT) in normal-weight healthy adults. METHODS: We carried out an analytical cross-sectional study in euthyroid non-diabetic adults, who attended the outpatient service of a private clinic in Lima-Peru from 2012 to 2016. Participants were divided in two groups according to the presence or absence of high TG/HDL-C ratio, IR or hyperinsulinemia after OGTT. TG/HDL-C ratio values ≥ 3 were considered as high. IR was defined as a Homeostasis Model Assessment (HOMA-IR) value ≥ 2.28 and hyperinsulinemia after OGTT as a serum insulin value ≥ 80µU/mL after 120 min of 75-g glucose intake. We elaborated crude and adjusted Poisson generalized linear models to evaluate the association between high TG/HDL-C ratio and IR or hyperinsulinemia after OGTT and reported the prevalence ratio (PR) with their respective 95% confidence intervals (95%CI). RESULTS: We analyzed the data of 118 individuals. Prevalence of high TG/HDL-C ratio was 17.8% (n = 21) while the prevalence of IR and hyperinsulinemia after OGTT was 24.6% (n = 29) and 17.0% (n = 20), respectively. TG/HDL-C-ratio values were positively correlated with HOMA-IR (r = 0.498; p < 0.01) and serum insulin after OGTT (r = 0.326; p < 0.001). In the adjusted model, high TG/HDL-C ratio was associated with both IR (aPR = 3.16; 95%CI: 1.80-5.77) and hyperinsulinemia after OGTT (aPR = 2.36; 95%CI: 1.20-4.63). CONCLUSIONS: High TG/HDL-C ratio was associated with both IR markers used in our study, appearing to be a clinically useful tool to assess IR in euthyroid normal-weight adults without type 2 diabetes mellitus.


Assuntos
Biomarcadores/sangue , HDL-Colesterol/sangue , Hiperinsulinismo/epidemiologia , Hipertrigliceridemia/epidemiologia , Resistência à Insulina , Triglicerídeos/sangue , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperinsulinismo/sangue , Hipertrigliceridemia/sangue , Masculino , Peru/epidemiologia , Prevalência , Prognóstico
7.
Diabetes Metab Syndr ; 13(1): 770-775, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641804

RESUMO

AIM: To evaluate the predictive accuracy of surrogate measures of fasting insulin resistance/sensitivity like the Homeostasis model assessment for insulin resistance (HOMA -IR), Fasting glucose/insulin ratio (FG-IR), Quantitative insulin sensitivity check index (QUICKI), and the 20/fasting C peptide x fasting plasma glucose [20/(FCP × FPG)] index in comparison to M value derived from hyperinsulinaemic-euglycaemic clamp (HEC) studies in two birth weight based cohorts of Asian Indian males. METHODS: HEC studies were performed in non-diabetic Asian Indian males (n = 117), born of normal birth weight (n = 59, birth weight > 2.5 kgs) and low birth weight (n = 58, birth weight < 2.5 kgs). Anthropometry and biochemical analysis were done. Surrogate indices of fasting insulin resistance were calculated and data were analysed by Pearson's correlation and Random calibration model analysis. RESULTS: Amongst surrogate indices of fasting insulin resistance/sensitivity, the mean values for HOMA-IR, QUICKI, FG-IR, 20/(FCP × FPG) index and M value were similar between the two groups. Significant positive correlation was observed for FG-IR and QUICKI with M value (the gold standard measure of insulin sensitivity derived from HEC procedure) in the low birth weight cohort in contrast to the normal birth weight cohort, wherein no significant correlation was observed for any of the indices. Random calibration model analysis showed highest predictive accuracy for QUICKI in both the study groups. CONCLUSION: The QUICKI index showed highest predictive accuracy in the normal birth weight and the low birth weight cohorts of Asian Indian males.


Assuntos
Grupo com Ancestrais do Continente Asiático , Peso ao Nascer/fisiologia , Jejum/sangue , Hiperinsulinismo/sangue , Recém-Nascido de Baixo Peso/sangue , Resistência à Insulina/fisiologia , Adolescente , Biomarcadores/sangue , Glicemia/metabolismo , Estudos de Coortes , Estudos Transversais , Teste de Tolerância a Glucose/métodos , Humanos , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/epidemiologia , Índia/epidemiologia , Recém-Nascido , Masculino , Adulto Jovem
8.
Biosci Biotechnol Biochem ; 83(4): 747-750, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30582404
9.
J. physiol. biochem ; 74(4): 667-677, nov. 2018. graf, ilus, tab
Artigo em Inglês | IBECS | ID: ibc-179044

RESUMO

The adrenomedullary chromaffin cells' hormonal pathway has been related to the pathophysiology of diabetes mellitus. In mice, the deletion of insulin receptor substrate type 2 (Irs2) causes peripheral insulin resistance and reduction in Beta-cell mass, leading to overt diabetes, with gender differences on adrenergic signaling. To further unravel the relevance of Irs2 on glycemic control, we analyzed in adult Irs2 deficient (Irs2-/-) mice, of both sexes but still normoglycemic, dopamine effects on insulin secretion and glycerol release, as well as their adrenal medulla by an immunohistochemical and morphologic approach. In isolated islets, 10 μM dopamine significantly inhibited insulin release in wild-type (WT) and female Irs2−/− mice; however, male Irs2−/− islets were insensitive to that catecholamine. Similarly, on isolated adipocytes, gender differences were observed between WT and Irs2-/- mice in basal and evoked glycerol release with crescent concentrations of dopamine. By immunohistochemistry, reactivity to tyrosine hydroxylase (TH) in female mice was significantly higher in the adrenal medulla of Irs2-/- compared to WT; although no differences for TH-immunopositivity were observed between the male groups of mice. However, compared to their corresponding WT animals, adrenomedullary chromaffin cells of Irs2-/- mice showed a significant decrease in the cellular and nuclear areas, and even in their percentage of apoptosis. Therefore, our observations suggest that, together with gender differences on dopamine responses in Irs2-/- mice, disturbances in adrenomedullary chromaffin cells could be related to deficiency of Irs2. Accordingly, Irs2 could be necessary for adequate glucose homeostasis and maintenance of the population of the adrenomedullary chromaffin cells


No disponible


Assuntos
Animais , Masculino , Feminino , Camundongos , Medula Suprarrenal/metabolismo , Dopamina/metabolismo , Hiperinsulinismo/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Estado Pré-Diabético/metabolismo , Adipócitos Brancos , Hiperinsulinismo/sangue , Hiperinsulinismo/patologia , Técnicas In Vitro , Proteínas Substratos do Receptor de Insulina/genética , Ilhotas Pancreáticas/patologia , Estado Pré-Diabético/patologia
10.
Pharm Biol ; 56(1): 302-308, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29952676

RESUMO

CONTEXT: Galangin, a natural flavonoid, is found in honey and Alpinia officinarum Hance (Zingiberaceae). Galangin has antiviral, antimicrobial, antidiabetic and anticancer properties, without side effects. The effects of galangin on hyperglycaemia and lipid abnormalities are not known. OBJECTIVE: To elucidate the effectiveness of galangin on hyperglycaemia-associated complications and lipid changes in rats with streptozotocin (STZ)-induced hyperglycaemia. MATERIALS AND METHODS: Diabetes was induced in adult Wistar rats by administering 40 mg/kg of STZ. In our previous study, galangin had no toxicity at concentrations up to 320 mg/kg. Therefore three doses of galangin (4, 8 or 16 mg/kg BW) or glibenclamide (600 µg/kg BW) were administered daily to diabetic rats orally for 45 days. RESULTS: Diabetic rats showed a significant (p < 0.05) increased levels of plasma glucose (281.10 mg/dL) and decreased levels of insulin (6.01 µU/mL). Additionally, diabetic rats showed a significant (p < 0.05) increased levels of plasma lipid profiles such as total cholesterol (149.05 mg/dL), triglycerides (143.28 mg/dL), free fatty acids (139.37 mg/dL), phospholipids (127.53 mg/dL), plasma low-density lipoprotein-cholesterol (98.72 mg/dL), plasma very low-density lipoprotein-cholesterol (28.65 mg/dL), and significant (p < 0.05) decreased in plasma high-density lipoprotein-cholesterol (21.68 mg/dL). When galangin was administered to the hyperglycaemic rats, plasma glucose and insulin levels and lipid profiles reverted to levels similar to those in healthy control rats. DISCUSSION AND CONCLUSIONS: Administration of galangin reduced hyperlipidaemia related to the risk of diabetic complications and could be beneficial for diabetic hyperlipidaemic patients. Further work detailing its mechanism-of-action for improving hyperglycaemic-associated lipid abnormalities is needed.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides/uso terapêutico , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Animais , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Hiperinsulinismo/sangue , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/tratamento farmacológico , Hiperlipidemias/sangue , Hiperlipidemias/induzido quimicamente , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Ratos , Ratos Wistar , Estreptozocina/toxicidade , Triglicerídeos/antagonistas & inibidores , Triglicerídeos/sangue
11.
Biomed Pharmacother ; 105: 182-186, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29857297

RESUMO

Fructose administration can induce hypertension, insulin resistance and hypertriglyceridemia. Here, we investigated the possible protective effect of infliximab (IFX), a tumor necrosis factor alpha (TNF-α) inhibitor, or tocilizumab (TOC), an interleukin-6 (IL6) inhibitor, on fructose-induced increase in blood pressure, insulin resistance and hyperlipidemia in rats. The animals were fed a 60% fructose diet in the absence or presence of IFX (5 mg/kg, i.p., once weekly) or TOC (8 mg/kg, i.p., once every two weeks). Fructose significantly increased blood pressure, heart rate and homeostatic model assessment of insulin resistance (HOMA-IR). Fructose also significantly raised the concentrations of fasting plasma insulin, triglycerides, total cholesterol, uric acid, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), malondialdhyde (MDA) and nitric oxide. Fructose also significantly decreased plasma superoxide dismutase (SOD) and catalase activities. In addition, fructose significantly increased aortic endothelin and nitric oxide concentrations. Both IFX and TOC attenuated the fructose-induced increase in blood pressure, insulin resistance, and the concentrations of uric acid, MDA and IL-6. TOC significantly reduced fructose-induced increase in triglycerides and cholesterol. In addition, IFX increased plasma SOD and catalase activities. Our results showed that both IFX and TOC were partially successful in reversing fructose - induced changes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Hiperinsulinismo/tratamento farmacológico , Hipertensão/tratamento farmacológico , Infliximab/uso terapêutico , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Aorta/metabolismo , Biomarcadores/sangue , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Catalase/metabolismo , Colesterol/sangue , Endotelina-1/metabolismo , Frutose , Frequência Cardíaca/efeitos dos fármacos , Hiperinsulinismo/sangue , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/fisiopatologia , Hipertensão/sangue , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Mediadores da Inflamação/sangue , Infliximab/farmacologia , Insulina/sangue , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/sangue , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Superóxido Dismutase/metabolismo , Triglicerídeos/sangue
12.
PLoS One ; 13(5): e0196895, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29718998

RESUMO

Although exercise is effective in improving obesity and hyperinsulinemia, the exact influence of exercise on the capillary density of skeletal muscles remains unknown. The aim of this study was to investigate the effects of low-intensity exercise training on metabolism in obesity with hyperinsulinemia, focusing specifically on the capillary density within the skeletal muscle. Otsuka Long-Evans Tokushima fatty (OLETF) rats were used as animal models of obesity with hyperinsulinemia, whereas Long-Evans Tokushima Otsuka (LETO) rats served as controls (no obesity, no hyperinsulinemia). The animals were randomly assigned to either non-exercise or exercise groups (treadmill running for 60 min/day, for 4 weeks). The exercise groups were further divided into subgroups according to training mode: single bout (60 min, daily) vs. multiple bout (three bouts of 20 min, daily). Fasting insulin levels were significantly higher in OLETF than in LETO rats. Among OLETF rats, there were no significant differences in fasting glucose levels between the exercise and the non-exercise groups, but the fasting insulin levels were significantly lower in the exercise group. Body weight and triacylglycerol levels in the liver were significantly higher in OLETF than in LETO rats; however, among OLETF rats, these levels were significantly lower in the exercise than in the non-exercise group. The capillary-to-fiber ratio of the soleus muscle was significantly higher in OLETF than in LETO rats; however, among OLETF rats, the ratio was lower in the exercise group than in the non-exercise group. No significant differences in any of the studied parameters were noted between the single-bout and multiple-bout exercise training modes among either OLETF or LETO rats. These results suggest that low-intensity exercise training improves insulin sensitivity and fatty liver. Additionally, the fact that attenuation of excessive capillarization in the skeletal muscle of OLETF rats was accompanied by improvement in increased body weight.


Assuntos
Capilares/patologia , Hiperinsulinismo/sangue , Músculo Esquelético/irrigação sanguínea , Obesidade/sangue , Adiponectina/sangue , Animais , Glicemia , Terapia por Exercício , Ácidos Graxos/sangue , Hiperinsulinismo/patologia , Hiperinsulinismo/terapia , Insulina/sangue , Metabolismo dos Lipídeos , Masculino , Músculo Esquelético/metabolismo , Obesidade/patologia , Obesidade/terapia , Ratos Endogâmicos OLETF , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue
13.
Diabetes ; 67(7): 1237-1245, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29666062

RESUMO

We observed that a 4-h morning (AM) duodenal infusion of glucose versus saline doubled hepatic glucose uptake (HGU) and storage during a hyperinsulinemic-hyperglycemic (HIHG) clamp that afternoon (PM). To separate the effects of AM hyperglycemia versus AM hyperinsulinemia on the PM response, we used hepatic balance and tracer ([3-3H]glucose) techniques in conscious dogs. From 0 to 240 min, dogs underwent a euinsulinemic-hyperglycemic (GLC; n = 7) or hyperinsulinemic-euglycemic (INS; n = 8) clamp. Tracer equilibration and basal sampling occurred from 240 to 360 min, followed by an HIHG clamp (360-600 min; four times basal insulin, two times basal glycemia) with portal glucose infusion (4 mg ⋅ kg-1 ⋅ min-1). In the HIHG clamp, HGU (5.8 ± 0.9 vs. 3.3 ± 0.3 mg ⋅ kg-1 ⋅ min-1) and net glycogen storage (6.0 ± 0.8 vs. 2.9 ± 0.5 mg ⋅ kg-1 ⋅ min-1) were approximately twofold greater in INS than in GLC. PM hepatic glycogen content (1.9 ± 0.2 vs. 1.3 ± 0.2 g/kg body weight) and glycogen synthase (GS) activity were also greater in INS versus GLC, whereas glycogen phosphorylase (GP) activity was reduced. Thus AM hyperinsulinemia, but not AM hyperglycemia, enhanced the HGU response to a PM HIHG clamp by augmenting GS and reducing GP activity. AM hyperinsulinemia can prime the liver to extract and store glucose more effectively during subsequent same-day meals, potentially providing a tool to improve glucose control.


Assuntos
Ritmo Circadiano/fisiologia , Glucose/metabolismo , Hiperinsulinismo/metabolismo , Glicogênio Hepático/metabolismo , Animais , Metabolismo dos Carboidratos , Cães , Feminino , Glicogênio/metabolismo , Hiperinsulinismo/sangue , Insulina/sangue , Fígado/metabolismo , Masculino , Fatores de Tempo
14.
Nutrients ; 10(2)2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29419785

RESUMO

Glycaemic index (GI) is used as an indicator to guide consumers in making healthier food choices. We compared the GI, insulin index (II), and the area under the curve for blood glucose and insulin as glucose (GR) and insulin responses (IR) of a newly developed liquid nutritional formula with one commercially available liquid product with different types of carbohydrates. We then evaluated the glucose and insulin responses of two test foods with comparable energy density and protein percentage but presented in different food forms (liquid vs. solid). Fourteen healthy women participated in the study. GI, II, GR, and IR were assessed after (independent) consumption of two liquid products and a solid breakfast meal. The two liquid foods showed comparable GI, whilst the liquid form appeared to produce lower median GI (25 vs. 54), and II (52 vs. 98) values compared to the solid breakfast (p < 0.02). The median GR and IR for solid breakfast were respectively 44% and 45% higher compared to the liquid product (p < 0.02). Liquid formulas with different carbohydrate qualities produced comparable glucose responses, while foods with comparable energy density and protein percentage but different food form elicited differential effects on GI, II, GR, and IR. Nutrient quality and food form need to be taken into consideration when developing low GI products to manage glycaemic responses.


Assuntos
Bebidas , Carboidratos da Dieta/uso terapêutico , Alimentos Formulados , Índice Glicêmico , Hiperglicemia/prevenção & controle , Hiperinsulinismo/prevenção & controle , Resistência à Insulina , Adulto , Área Sob a Curva , Bebidas/efeitos adversos , Biomarcadores/sangue , Glicemia/análise , Desjejum , Estudos Cross-Over , Dieta/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Carboidratos da Dieta/metabolismo , Digestão , Feminino , Alimentos Formulados/efeitos adversos , Humanos , Hiperglicemia/sangue , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperinsulinismo/sangue , Hiperinsulinismo/etiologia , Hiperinsulinismo/metabolismo , Insulina/sangue , Valor Nutritivo , Período Pós-Prandial , Reprodutibilidade dos Testes , Adulto Jovem
15.
Nutrients ; 10(2)2018 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-29373530

RESUMO

Resistant starch (RS) is a type of dietary fiber that has been acknowledged for multiple physiological benefits. Resistant starch type 4 (RS4) is a subcategory of RS that has been more intensively studied as new types of RS4 emerge in the food supply. The primary aim of this randomized, double-blind, controlled study was to characterize the postprandial glucose response in healthy adults after consuming a high fiber scone containing a novel RS4 or a low fiber control scone without RS4. Secondary aims included assessment of postprandial insulin response, postprandial satiety, and gastrointestinal tolerance. The fiber scone significantly reduced postprandial glucose and insulin incremental areas under the curves (43-45% reduction, 35-40% reduction, respectively) and postprandial glucose and insulin maximum concentrations (8-10% and 22% reduction, respectively). The fiber scone significantly reduced hunger and desire to eat during the 180 min following consumption and yielded no gastrointestinal side effects compared with the control scone. The results from this study demonstrate that a ready-to-eat baked-good, such as a scone, can be formulated with RS4 replacing refined wheat flour to yield statistically significant and clinically meaningful reductions in blood glucose and insulin excursions. This is the first study to report increased satiety after short-term RS4 intake, which warrants further investigation in long-term feeding studies.


Assuntos
Pão , Dieta com Restrição de Carboidratos , Fibras na Dieta/administração & dosagem , Alimentos Fortificados , Índice Glicêmico , Resposta de Saciedade , Amido/análogos & derivados , Adolescente , Adulto , Idoso , Dieta com Restrição de Carboidratos/efeitos adversos , Fibras na Dieta/efeitos adversos , Fibras na Dieta/metabolismo , Método Duplo-Cego , Feminino , Manipulação de Alimentos , Preferências Alimentares , Temperatura Alta , Humanos , Hidrólise , Hiperglicemia/sangue , Hiperglicemia/prevenção & controle , Hiperinsulinismo/sangue , Hiperinsulinismo/prevenção & controle , Masculino , Pessoa de Meia-Idade , Amido/administração & dosagem , Amido/efeitos adversos , Amido/metabolismo , Adulto Jovem
16.
J Diabetes ; 10(5): 357-364, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29281182

RESUMO

BACKGROUND: The aim of this study was to investigate the association between branched-chain amino acid (BCAA) intake and markers of insulin metabolism in adults. METHODS: This cohort study was conducted within the framework of the Tehran Lipid and Glucose Study on 1205 subjects, aged ≥20 years, who were followed-up for a mean of 2.3 years. Dietary intake of BCAAs, including valine, leucine, and isoleucine, was determined using a valid and reliable food frequency questionnaire. Hyperinsulinemia, ß-cell dysfunction, insulin resistance (IR), and insulin insensitivity were determined according to optimal cut-off values. Logistic regression was to estimate the occurrence of IR across tertiles of BCAA intake. RESULTS: The mean (± SD) age and BCAA intake of participants (43% male) at baseline were 42.7 ± 13.1 years and 13.8 ± 5.1 g/day, respectively. The incidence of hyperinsulinemia, ß-cell dysfunction, insulin insensitivity, and IR was 19.5%, 24.0%, 28.0%, and 12.5%, respectively. After adjustment for confounding variables, subjects in the highest tertile for total BCAAs (odds ratio [OR] 1.67; 95% confidence interval [CI] 1.03-2.71), leucine (OR 1.75; 95% CI 1.09-2.82), and valine (OR 1.61; 95% CI 1.01-2.60) intake had a greater risk of incident IR than subjects in the lowest tertile. A higher intake of isoleucine was not associated with risk of incident IR. There was no association of total BCAAs, leucine, isoleucine, and valine intake with the risk of hyperinsulinemia, insulin insensitivity, or ß-cell dysfunction. CONCLUSION: The findings of this study support the hypothesis that higher intakes of BCAAs may have adverse effects on the development of IR.


Assuntos
Aminoácidos de Cadeia Ramificada/efeitos adversos , Glicemia/metabolismo , Dieta Rica em Proteínas/efeitos adversos , Resistência à Insulina , Insulina/sangue , Adulto , Aminoácidos de Cadeia Ramificada/administração & dosagem , Aminoácidos de Cadeia Ramificada/metabolismo , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/epidemiologia , Incidência , Células Secretoras de Insulina/metabolismo , Irã (Geográfico)/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
17.
Reprod Biomed Online ; 36(2): 172-180, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29217128

RESUMO

There is growing interest in exploring circulating (plasma/serum) irisin in polycystic ovary syndrome (PCOS) patients. This meta-analysis aimed to summarize the evidence assessing circulating irisin changes in this population. A systematic search was conducted in three databases: PubMed, Cochrane Library and Web of Science, for studies reporting irisin in PCOS patients compared with healthy controls or stratified by body mass index (BMI), or assessing irisin response to hyperinsulinemia. Effect sizes (Cohen's d with 95% confidence intervals [CI]) were calculated using random-effects models. Eight studies with 918 PCOS patients and 528 healthy controls were included. Results showed that circulating irisin was higher in PCOS patients than in overall healthy controls (d = 0.37, 95% CI 0.05 to 0.70), but not compared with BMI-matched or age- and BMI-matched controls. Circulating irisin was higher in PCOS patients with higher BMI than lower (d = 0.36, 95% CI 0.16 to 0.56). Circulating irisin decreased 2 h later in response to euglycemic hyperinsulinemia in PCOS patients with a larger magnitude than healthy controls (d = -0.32, 95% CI -0.53 to -0.11). In summary, with adjustment for BMI, circulating irisin in PCOS patients seems comparable to healthy controls, but its response to hyperinsulinemia might be impaired.


Assuntos
Fibronectinas/sangue , Síndrome do Ovário Policístico/sangue , Feminino , Técnica Clamp de Glucose , Humanos , Hiperinsulinismo/sangue , Estudos Observacionais como Assunto
18.
Arch Physiol Biochem ; 124(4): 300-305, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29113498

RESUMO

BACKGROUND: Recently, much attention has been paid to the role of circulating microRNAs (miRNAs) as novel biomarkers for various diseases. The aim of this study was to investigate the level of a subset of miRNAs in serum samples of the diabetic and healthy subjects. METHODS: Forty two healthy and 45 T2D subjects participated in this study. Serum miR-21, miR-126, and miR-146a levels were measured using real-time PCR. RESULTS: There was no significant difference in the serum level of miR-21, miR-126, and miR-146a between the diabetic and non-diabetic groups. The level of miR-21 in obese non-diabetic and diabetic subjects was significantly lower than lean subjects. Correlation analyses in non-diabetic and diabetic groups revealed a significant negative correlation between the amount of miR-21 and body mass index, waist circumference, insulin, and HOMA-IR levels. CONCLUSIONS: A reduced level of miR-21 might associate with obesity and its related metabolic traits such as hyperinsulinaemia.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Regulação para Baixo , Resistência à Insulina , MicroRNAs/sangue , Obesidade/sangue , Adulto , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobina A Glicada/análise , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/complicações , Hiperinsulinismo/epidemiologia , Hiperinsulinismo/metabolismo , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Fatores de Risco , Circunferência da Cintura
19.
Arch Physiol Biochem ; 124(4): 306-312, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29113509

RESUMO

CONTEXT: We have previously shown that an antidepressant-like effect of probiotics in rats was associated with a higher plasma level of the microbial tryptophan metabolite indole-3-propionic acid (IPA). OBJECTIVE: We therefore wanted to study the isolated effect of IPA on behaviour and glucose metabolism in rats. METHODS: Male Sprague-Dawley rats were fed control or IPA-enriched diet for six weeks (n = 12 per group) and assessed in the elevated plus maze, open field and forced swim test. Blood glucose, metabolic hormones and the white blood cell (WBC) composition were analysed. RESULTS: IPA (mean intake 27.3 mg/kg/day) significantly lowered fasting blood glucose level by 0.42 mM (95% CI 0.11-0.73). Similarly, fasting plasma insulin levels and the homeostatic model assessment (HOMA) index of insulin resistance were reduced, whereas plasma metabolic hormones, behaviour and WBC composition remained unaffected by IPA. CONCLUSIONS: Our findings highlight IPA as a promising candidate for treatment of metabolic disorders associated with insulin resistance.


Assuntos
Suplementos Nutricionais , Hiperinsulinismo/prevenção & controle , Hipoglicemiantes/uso terapêutico , Indóis/uso terapêutico , Resistência à Insulina , Estado Pré-Diabético/prevenção & controle , Propionatos/uso terapêutico , Animais , Ansiedade/sangue , Ansiedade/imunologia , Ansiedade/metabolismo , Ansiedade/prevenção & controle , Comportamento Animal , Glicemia/análise , Depressão/sangue , Depressão/imunologia , Depressão/metabolismo , Depressão/prevenção & controle , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/prevenção & controle , Suplementos Nutricionais/efeitos adversos , Hiperinsulinismo/sangue , Hiperinsulinismo/imunologia , Hiperinsulinismo/metabolismo , Hipoglicemiantes/efeitos adversos , Indóis/efeitos adversos , Insulina/sangue , Contagem de Leucócitos , Masculino , Estado Pré-Diabético/sangue , Estado Pré-Diabético/imunologia , Estado Pré-Diabético/metabolismo , Propionatos/efeitos adversos , Distribuição Aleatória , Ratos Sprague-Dawley
20.
J Med Food ; 21(3): 269-273, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28976801

RESUMO

Alpha-lipoic acid (ALA) is known to lower insulin resistance (IR), which is common among migraineurs. To assess the effect of ALA on headache in migraineurs with IR, we performed an exploratory study on a cohort of patients with migraine, followed at our Headache Center. The 32 patients took ALA 400 mg b.i.d. for 6 months in addition to their on-going treatment. The percentage of patients with a reduction of at least 50% of the attacks was 0.53 (confidence interval [95% CI] 0.36-0.70) at 2 months, 0.56 (0.39-0.73) at 4 months, and 0.69 (0.53-0.85) at 6 months. The incidence rate ratio of attacks at 6 months versus baseline was 0.48 (0.43-0.53, P < .001), corresponding to a mean (95% CI) number of attacks of 5 (4-6) versus 11 (10-12). The number of days of treatment in the previous month was 7.7 (6.8-8.7) at baseline, 5.4 (4.6-6.2) at 2 months, 5.3 (4.5-6.1) at 4 months, and 4.3 (3.6-5.0) at 6 months. Baseline and 120-min glucose and insulin and quantitative insulin sensitivity check index (QUICKI) and the Stumvoll index did not change at 6 months versus baseline. This exploratory study shows that the administration of ALA may be associated with a reduction in the number of attacks and the days of treatment in migraineurs with IR. A randomized controlled trial is needed to test this possibility.


Assuntos
Antioxidantes/uso terapêutico , Hiperinsulinismo/dietoterapia , Resistência à Insulina , Enxaqueca com Aura/dietoterapia , Enxaqueca sem Aura/dietoterapia , Ácido Tióctico/uso terapêutico , Adulto , Biomarcadores/sangue , Glicemia/análise , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Teste de Tolerância a Glucose , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/complicações , Hiperinsulinismo/metabolismo , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Enxaqueca com Aura/complicações , Enxaqueca com Aura/fisiopatologia , Enxaqueca com Aura/terapia , Enxaqueca sem Aura/complicações , Enxaqueca sem Aura/fisiopatologia , Enxaqueca sem Aura/terapia , Ambulatório Hospitalar , Índice de Gravidade de Doença
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