Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 135
Filtrar
1.
Nutr Metab Cardiovasc Dis ; 27(7): 601-608, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28511905

RESUMO

BACKGROUND AND AIMS: A link between increased blood viscosity and type 2 diabetes has been previously reported. Herein, we investigated the association of blood viscosity with prediabetes, identified by glycated hemoglobin A1c (HbA1c) according to the new American Diabetes Association criteria, and subclinical atherosclerosis. METHODS AND RESULTS: The study cohort includes 1136 non-diabetic adults submitted to anthropometrical evaluation, an oral glucose tolerance test and ultrasound measurement of carotid intima-media thickness (IMT). Whole blood viscosity was estimated using a validated formula based on hematocrit and total plasma proteins. After adjusting for age, and gender, individuals with HbA1c-defined prediabetes (HbA1c 5.7-6.4% [39-47 mmol/mol]) exhibited significantly higher values of hematocrit, and predicted blood viscosity as compared with controls. Increased levels of IMT were observed in subjects with HbA1c-defined prediabetes in comparison to controls. Predicted blood viscosity was positively correlated with age, waist circumference, blood pressure, cholesterol, triglycerides, fibrinogen, white blood cell, HbA1c, fasting and 2-h post-load glucose levels, fasting insulin, IMT and inversely correlated with HDL and Matsuda index of insulin sensitivity. Of the three glycemic parameters, i.e. HbA1c, fasting and 2-h post-load glucose, only HbA1c showed a significant correlation with predicted blood viscosity (ß = 0.054, P = 0.04) in a multivariate regression analysis model including multiple atherosclerosis risk factors. CONCLUSION: The study shows that individuals with HbA1c-defined prediabetes have increased predicted blood viscosity and IMT. The HbA1c criterion may be helpful to capture individuals with an increased risk of diabetes and cardiovascular disease who may benefit from an intensive lifestyle intervention.


Assuntos
Viscosidade Sanguínea , Doenças Cardiovasculares/etiologia , Hemoglobinas Glicadas/análise , Hemorreologia , Estado Pré-Diabético/sangue , Estado Pré-Diabético/fisiopatologia , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/fisiopatologia , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
2.
Nutr Metab Cardiovasc Dis ; 24(1): 27-33, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23601331

RESUMO

BACKGROUND AND AIMS: The A1C diagnostic criterion for identifying individuals at increased risk for diabetes, introduced by the American Diabetes Association in 2010, was not defined on the basis of the principal pathophysiological abnormalities responsible for the development and progression of type 2 diabetes; we therefore wished to gain a deeper insight into the metabolic abnormalities characterizing the group of at risk individuals with an A1C value of 5.7-6.4%. METHODS AND RESULTS: As many as 338 non-diabetic offspring of type 2 diabetic patients were consecutively recruited. Insulin secretion was assessed using both indexes derived from oral glucose tolerance test (OGTT), and intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. As compared with subjects with A1C <5.7%, individuals with A1C of 5.7-6.4% exhibited lower insulin sensitivity after adjusting for age, gender and body mass index (BMI). Insulin secretion estimated from the OGTT, did not differ between the two groups. By contrast, as compared with subjects with A1C <5.7%, the acute insulin response (AIR) during an IVGTT and both IVGTT-derived and OGTT-derived disposition indexes were reduced in individuals with A1C of 5.7-6.4% after adjusting for age, gender and BMI. As A1C increased to ≥ 5.7%, a sharp decrease in insulin sensitivity and ß-cell function, measured as disposition index, was observed. CONCLUSIONS: Caucasian individuals with A1C ≥ 5.7% exhibit both core pathophysiological defects of type 2 diabetes i.e. insulin resistance and ß-cell dysfunction.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobinas Glicadas/metabolismo , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Humanos , Insulina/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-Idade
3.
Nutr Metab Cardiovasc Dis ; 24(12): 1365-72, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25149895

RESUMO

BACKGROUND AND AIMS: Low insulin-like growth factor-1 (IGF-1) levels and high uric acid concentrations are associated with cardio-metabolic disorders. Acute IGF-1 infusion decreases uric acid concentration in healthy individuals. In this study, we aimed to examine the relationship between IGF-1 and uric acid levels. METHODS AND RESULTS: 1430 adult non diabetic subjects were stratified into quartiles according to their circulating IGF-1 values. Significant differences in uric acid concentration, measured by the URICASE/POD method were observed between low (quartile 1), intermediate (quartile 2 and 3), and high (quartile 4) IGF-1 levels groups after adjusting for age, gender, and body mass index (P = 0.02). These differences remained significant after adjustment for blood pressure, total cholesterol, high density lipoprotein, triglycerides, fasting and 2 h post-load glucose levels, HOMA-IR index (P = 0.005), liver enzymes (P = 0.03), glucose tolerance status (P = 0.02), growth hormone levels (GH) (P = 0.05), anti-hypertensive treatments (P = 0.04) or diuretics use (P = 0.04)). To clarify the molecular links between IGF-1 and uric acid, we performed an in vitro study, incubating human hepatoma cells with uric acid for 24 or 48 h in the presence of GH and observed a 21% and 26% decrease, respectively, in GH-stimulated IGF-1 mRNA expression (P = 0.02 and P = 0.012, respectively). This effect appears to be mediated by uric acid ability to down regulate GH intracellular signaling; in fact we observed a significant decrease of GH activated JAK2 and Stat5 phosphorylation. CONCLUSIONS: These data demonstrate an inverse relationship between IGF-1 and uric acid levels in adults and suggest that uric acid might affect hepatic IGF-1 synthesis.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Ácido Úrico/sangue , Adulto , Idoso , Antropometria , Glicemia/metabolismo , Linhagem Celular Tumoral , Estudos de Coortes , Feminino , Teste de Tolerância a Glucose , Hormônio do Crescimento Humano/sangue , Humanos , Lipídeos/sangue , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco
4.
Nutr Metab Cardiovasc Dis ; 22(7): 561-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21944738

RESUMO

BACKGROUND AND AIMS: The American Diabetes Association (ADA) has revised criteria for diagnosis of type 2 diabetes recommending an A1C cut point of ≥6.5% in addition to criteria based on glucose levels. We compared A1C, fasting plasma glucose (FPG) or 2-h post-challenge glucose (2-hPG) criteria for the diagnosis of diabetes in a cohort of Italian Caucasians. METHODS AND RESULTS: A total of 1019 individuals without known diabetes completed an oral glucose tolerance test (OGTT) and had A1C measured. Moderate agreement existed for A1C and FPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.522), with 85.5% of individuals classified as not having diabetes by both A1C and FPG criteria, and 5.8% classified as having diabetes by both A1C and FPG criteria. Discordant classifications occurred for 5.5% of individuals who had an A1C ≥ 6.5% and FPG <126 mg dl(-1), and for 3.2% who had an A1C <6.5% and FPG ≥126 mg dl(-1). Modest agreement existed for A1C and 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.427), with 81.8% of individuals classified as not having diabetes by both A1C and 2-hPG criteria, and 6.0% classified as having diabetes by both A1C and 2-hPG criteria. The area under the receiver operating characteristic curve of A1C for identifying subjects with diabetes according to FPG or 2-hPG criteria was 0.856 and 0.794, respectively. Modest agreement existed for A1C and FPG and/or 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.446). CONCLUSIONS: A1C ≥ 6.5% demonstrates a moderate agreement with fasting glucose and 2-hPG for diagnosing diabetes among adult Italian Caucasians subjects.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobinas Glicadas/análise , População Branca , Adulto , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Jejum , Feminino , Teste de Tolerância a Glucose , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco
5.
Diabetologia ; 54(4): 795-802, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21234743

RESUMO

AIMS/HYPOTHESIS: The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry. METHODS: Sample 1 comprised 845 non-diabetic offspring of type 2 diabetes patients recruited in five European centres participating in the EUGENE2 study. Samples 2 and 3 comprised, respectively, 864 and 524 Italian non-diabetic participants. All individuals underwent an OGTT. Screening for the rs10811661 polymorphism was performed using a TaqMan allelic discrimination assay. RESULTS: The rs10811661 polymorphism did not show a significant association with age, BMI and insulin sensitivity. Participants carrying the TT genotype showed a significant reduction in insulin release, measured by an OGTT-derived index, compared with carriers of the C allele, in the three samples. When these results were pooled with those of three published studies, and meta-analysed with a random-effects model, the T allele was significantly associated with reduced insulin secretion (-35.09 [95% CI 14.68-55.52], p = 0.0008 for CC+CT vs TT; and -29.45 [95% CI 9.51-49.38], p = 0.0038, for the additive model). In addition, in our three samples, participants carrying the TT genotype exhibited an increased risk for impaired glucose tolerance (IGT) compared with carriers of the C allele (OR 1.55 [95% CI 1.20-1.95] for the meta-analysis of the three samples). CONCLUSIONS/INTERPRETATION: Our data, together with the meta-analysis of previously published studies, show that the rs10811661 polymorphism is associated with impaired insulin release and IGT, suggesting that this variant may contribute to type 2 diabetes by affecting beta cell function.


Assuntos
Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Resistência à Insulina/genética , Insulina/metabolismo , Polimorfismo Genético/genética , Adulto , Diabetes Mellitus Tipo 2/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA
6.
Nutr Metab Cardiovasc Dis ; 19(10): 713-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19346116

RESUMO

BACKGROUND AND AIM: Weight gain is associated with a decline in insulin sensitivity and a compensatory increase in insulin secretion. IGF-1 is a plausible candidate to explain these divergent phenomena. In this cross-sectional study, we analyzed the relationship between IGF-1 levels, insulin sensitivity and secretion in 110 nondiabetic subjects with a wide range of BMI to verify this hypothesis. METHODS AND RESULTS: Subjects underwent OGTT, IVGTT and euglycemic-hyperinsulinemic clamp. HOMA-beta, IVGTT-derived and OGTT-derived indexes for first-phase and second-phase insulin secretion were higher in obese as compared with overweight and normal-weight groups, while glucose disposal was lower. IGF-1 levels were negatively correlated with IVGTT-derived and OGTT-derived indexes first-phase and second-phase insulin secretion, and positively correlated with glucose disposal. These correlations were no longer significant after adjustment for BMI. In a multivariate analysis, the variables associated with glucose disposal were IGF-1, age, triglycerides, and 2-h post-load glucose accounting for 23.4% of its variation. When BMI was entered into the model, the variables associated with glucose disposal were triglycerides, 2-h post-load glucose and BMI accounting for 27.2% of variation. In a multivariate analysis, the only variable associated with IVGTT-derived first-phase and second-phase insulin secretion was IGF-1 accounting for 10.4% and 15.1% of variation, respectively. When BMI was entered into the model, it became the only variable associated with both first-phase and second-phase insulin secretion accounting for 25.7% and 37.6% of variation, respectively. CONCLUSION: These data suggest that progressive reduction in IGF-1 levels may be involved in obesity-related changes in both insulin sensitivity and secretion.


Assuntos
Adiposidade , Resistência à Insulina , Fator de Crescimento Insulin-Like I/análise , Insulina/metabolismo , Adulto , Idoso , Envelhecimento , Glicemia/análise , Índice de Massa Corporal , Estudos Transversais , Feminino , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Sobrepeso/sangue , Sobrepeso/complicações , Triglicerídeos/sangue , População Branca , Adulto Jovem
7.
Braz J Biol ; 67(3): 537-40, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18094838

RESUMO

Nest and or nest site reuse within and between breeding seasons was reported by the Euler's Flycatcher (Lathrotriccus euleri), the Sepia-capped Flycatcher (Leptopogon amaurocephalus) and the Gray-hooded Flycatcher (Mionectes -rufiventris) in forest fragments from southeastern Brazil. Nest and or nest site reuse between some years was frequent within a single breeding season by the Sepia-capped Flycatcher. Nest reuse, however, was not related to nesting success in the previous breeding attempt. Nest turnover rates (movement to a new site between years) were low for L. amaurocephalus, intermediate for L. euleri and high for M. rufiventris.


Assuntos
Comportamento de Nidação/fisiologia , Aves Canoras/fisiologia , Animais , Feminino , Estações do Ano
8.
Braz J Biol ; 67(4 Suppl): 873-82, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18278354

RESUMO

The Thamnophilus punctatus complex has been recently reviewed on the basis of morphological and vocal characters, and is divided in six different species. Two of the new species, although well defined on the basis of morphological differences, could not be unambiguously distinguished through their loud songs. The Planalto Slaty-antshrike (Thamnophilus pelzelni) and the Sooretama Slaty-antshrike (T. ambiguus) are most easily distinguished by subtle and localized changes in plumage colors of males and females. In the present study we used sequences of the control region, Cytochrome b, and ND2 genes, of the mitochondrial DNA (mtDNA) to evaluate the levels of molecular differentiation between these two species. The mean pairwise distance between the two species was 3.8%, while it varied from 2.7% to 4.9% for each mtDNA region. Although extensive variation was also detected among haplotypes within species, especially for T. ambiguus, we suggest that the genetic divergence found between T. ambiguus and T. pelzelni is high enough to corroborate the separate species status of these two antbird taxa.


Assuntos
DNA Mitocondrial/genética , Variação Genética/genética , Passeriformes/genética , Animais , Sequência de Bases , Feminino , Marcadores Genéticos/genética , Masculino , Dados de Sequência Molecular , Passeriformes/classificação , Análise de Sequência de DNA
9.
Braz J Biol ; 67(4 Suppl): 859-65, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18278352

RESUMO

Forest fragmentation affects bird populations in many ways, modifying the composition of communities and favouring open country species. The Atlantic Forest is considered one of the most important biomes in the world, due to its great biodiversity, accelerated rates of deforestation, and high endemism. Despite these characteristics, few studies have evaluated the effects of forest fragmentation in the genetic structure of Atlantic forest bird populations. So, this study aims to verify the effects of forest fragmentation in the genetic population structure of Conopophaga lineata, through RAPD markers. To achieve this goal, 89 C. lineata individuals were captured in nine Atlantic Forest fragments in Minas Gerais State. The RAPD data indicate that forest fragmentation has not affected the genetic variation of C. lineata populations (Mann-Whitney U=3.50; p=0.11). Great part of the genetic variability of this species is found within populations and it was not observed a correlation between genetic and geographic distance (Mantel test t=0.6250; p=073). UPGMA analyses did not show defined clades and all branches showed low statistical support. The low population differentiation observed in this species can be due to a high gene flow among populations or a recent fragmentation. Thus, the current diversity status of C. lineata populations indicates that this species is not significantly affected by fragmentation. However, more genetic studies are essential to improve conservation strategies of Brazilian Atlantic Forest birds.


Assuntos
Variação Genética/genética , Passeriformes/genética , Árvores , Análise de Variância , Animais , Brasil , Passeriformes/classificação , Reação em Cadeia da Polimerase , Técnica de Amplificação ao Acaso de DNA Polimórfico
10.
Biochim Biophys Acta ; 1036(3): 202-6, 1990 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-2257276

RESUMO

Erythrocytes, suspended in a glucose-containing buffer, catalyzed the partial reduction of extracellular methemoglobin. Physiological concentrations of ascorbic acid or dehydroascorbic acid greatly enhanced the rate of reaction and the ultimate extent of reduction. The relationship between erythrocyte concentration and initial reaction rate was nonlinear, which suggested that the rate limiting factor was not an erythrocyte membrane enzyme. Also, significant dehydroascorbate-stimulated reduction occurred even when the erythrocytes and methemoglobin were separated by a dialysis membrane. The above observations indicate that the transfer of reducing equivalents across the erythrocyte membrane and reduction of extracellular methemoglobin can be accomplished by release and recycling of ascorbic acid.


Assuntos
Eritrócitos/metabolismo , Metemoglobina/metabolismo , Oxirredutases/metabolismo , Ácido Ascórbico/metabolismo , Membrana Eritrocítica/metabolismo , Eritrócitos/enzimologia , Humanos , Oxirredução
11.
Diabetes ; 41(1): 6-11, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1727740

RESUMO

The IgG from a patient (Italy 2 [I2]) with hypoglycemia, due to autoantibodies to the insulin receptor, was purified on protein A Sepharose into two fractions that were tested in various human tissues and cells. The IgG fraction that bound protein A (absorbed IgG [IgGa]) nearly completely inhibited the binding of 125I-labeled insulin to various cells or tissues (placenta, IM-9, adipocytes, HEp-2-larynx cells, Epstein-Barr virus lymphocytes) but not greater than 50% of 125I-labeled insulin binding to human liver membranes. Conversely, both the IgG fraction from this patient, which did not bind protein A (flow-through IgG [IgGb]), and the IgGa fraction from a second similar patient (Italy 1 [I-1]) almost completely inhibited the binding of 125I-labeled insulin to liver membranes. The IgGa fraction from patient I-2 did not change receptor affinity because 50% inhibition of 125I-labeled insulin binding was not affected by either the presence or absence of these IgG fractions. Furthermore, liver binding data were not due to cross-reaction of 125I-labeled insulin to the insulinlike growth factor I receptor, and treatment of liver membranes with neuraminidase did not alter the inhibitory effect of the IgGa fraction from patient I-2 on 125I-labeled insulin binding to liver. Binding inhibition experiments performed with cells transfected with and overexpressing the -12 (human insulin receptor [HIR]-A) or the +12 (HIR-B) variant of HIR revealed that the IgGa fraction from patient I-2 inhibited 125I-labeled insulin binding to the HIR-A receptor but not to the HIR-B receptor.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Variação Genética , Imunoglobulina G , Receptor de Insulina/genética , Tecido Adiposo/metabolismo , Anticorpos Monoclonais , Linhagem Celular , Membrana Celular/metabolismo , Feminino , Humanos , Hipoglicemia/imunologia , Imunoglobulina G/classificação , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Cinética , Fígado/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Substâncias Macromoleculares , Placenta/metabolismo , Gravidez , Receptor de Insulina/imunologia , Receptor de Insulina/metabolismo
12.
Braz J Biol ; 75(1): 191-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25945637

RESUMO

Suitability of degraded areas as breeding habitats can be tested through assessment of nest predation rates. In this study we estimated nest success in relation to several potential predictors of nest survival in the Stripe-tailed Yellow-finch (Sicalis citrina) breeding in abandoned mining pits at Brasília National Park. We monitored 73 nests during the 2007-breeding season. Predation was the main cause of nest failure (n = 48, 66%); while six nests were abandoned (8%) and 19 nests produced young (26%). Mayfield's daily survival rates and nest success were 0.94 and 23%, respectively. Our results from nest survival models on program MARK indicated that daily survival rates increase linearly towards the end of the breeding season and decrease as nests aged. None of the nest individual covariates we tested - nest height, nest size, nest substrate, and edge effect - were important predictors of nest survival; however, nests placed on the most common plant tended to have higher survival probabilities. Also, there was no observer effect on daily survival rates. Our study suggests that abandoned mining pits may be suitable alternative breeding habitats for Striped-tailed Yellow-finches since nest survival rates were similar to other studies in the central cerrado region.


Assuntos
Ecossistema , Tentilhões/fisiologia , Comportamento de Nidação/fisiologia , Reprodução/fisiologia , Animais , Brasil , Feminino , Tentilhões/classificação , Masculino , Estações do Ano
13.
Mol Cell Endocrinol ; 86(1-2): 111-8, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1511777

RESUMO

Androgen receptors have been found in human larynx and androgens have been supposed to play an important role in promoting the growth of laryngeal carcinomas. The molecular mechanism underlaying this phenomenon is not at all understood. Aim of this work was to investigate the effects of two androgens (testosterone and dihydrotestosterone) on insulin receptor mRNA levels and insulin binding activity as well as on either metabolic or growth-promoting actions of insulin in a human larynx carcinoma cell line (HEp-2). We found that HEp-2 cells express a high affinity insulin receptor. Both androgens significantly increase insulin receptor mRNA levels and insulin receptor number in HEp-2 cells. Insulin action, evaluated either as total glucose utilization or as [3H]thymidine incorporation into DNA, significantly increased in HEp-2 treated with androgens in comparison to control cultures. Altogether, our data allow us to speculate that the increased insulin effectiveness we observed in the larynx carcinoma cell line HEp-2 after androgen treatment might be involved in the regulation of larynx cancer cells growth.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Di-Hidrotestosterona/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Insulina/metabolismo , Neoplasias Laríngeas/metabolismo , RNA Mensageiro/biossíntese , Receptor de Insulina/biossíntese , Testosterona/farmacologia , Carcinoma de Células Escamosas/patologia , Divisão Celular/efeitos dos fármacos , Humanos , Insulina/farmacologia , Neoplasias Laríngeas/patologia , Receptor de Insulina/efeitos dos fármacos , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Regulação para Cima/efeitos dos fármacos
14.
Mol Cell Endocrinol ; 135(1): 41-7, 1997 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-9453239

RESUMO

Insulin/IGF-I hybrid receptors composed of an insulin receptor (IR) alphabeta-hemireceptor and a type 1 IGF receptor (IGF-IR) alphabeta-hemireceptor are formed in tissues expressing both molecules. To date there is a limited information about the proportion of hybrids in tissues of normal or diabetic subjects. In this study, we determined the abundance of hybrids in fat from control and NIDDM subjects by using a microwell-based immunoassay. Microwells coated with MA-20 anti-IR or alpha-IGF-IR-PA anti-IGF-IR antibody were incubated with tissue extracts. Immunoadsorbed receptors were incubated with 125I-insulin or 125I-IGF-I in the presence or absence of unlabeled ligands, and hybrids were quantitated as the fraction of 125I-IGF-I binding immunoadsorbed with MA-20. Abundance of hybrids was increased in NIDDM patients as compared with controls (B/T = 1.29 +/- 0.18 and 0.52 +/- 0.06%; P < 0.008, respectively), and it was inversely correlated with both IR number (r = -0.65; P < 0.002), and in vivo insulin sensitivity measured by insulin tolerance test (r = -0.75; P < 0.005), whereas it was positively correlated with insulinemia (r = 0.63; P < 0.003). Insulin binding affinity was lower in NIDDM subjects than in controls (ED50 = 1.87 +/- 0.32 and 0.54 +/- 0.20 nmol/l; P < 0.009, respectively), and was correlated with the percentage of hybrids. Maximal IGF-I binding was significantly greater in NIDDM patients than controls and was positively correlated with the percentage of hybrids whereas IGF-I binding affinity did not differ between the two groups. Results show that expression of hybrids is increased in fat of NIDDM patients compared to control subjects and is correlated with in vivo insulin sensitivity thus raising the possibility that alterations in expression of hybrids which bind IGF-I with higher affinity than insulin may contribute, at least in part, to insulin resistance.


Assuntos
Tecido Adiposo/química , Diabetes Mellitus Tipo 2/metabolismo , Receptor IGF Tipo 1/análise , Receptor de Insulina/análise , Idoso , Feminino , Humanos , Imunoensaio , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Receptor de Insulina/metabolismo
15.
Mol Cell Endocrinol ; 101(1-2): 121-7, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-9397944

RESUMO

The insulin receptor exists in two isoforms differing by the absence (HIR-A) or presence (HIR-B) of 12 amino acids in the C-terminus of the alpha-subunit as a consequence of alternative splicing of exon 11. It was shown that the two isoforms exhibit different binding affinities for insulin, thus suggesting that the sequence encoded by exon 11 may be important for insulin binding. To further investigate this issue, we generated polyclonal antibodies against C-terminal peptides of the two HIR alpha-subunit variants. Herein, we characterized two antibodies, PA-11 and PA-12, directed against the C-terminus or the N-terminus of the sequence encoded by exon 11, respectively, and one (PA-13) directed against a sequence in the carboxy-terminal region of the alpha-subunit which is common to HIR-A and HIR-B. Antibodies were characterized for their ability to immunoprecipitate the receptor and to inhibit [125I]insulin binding to both isoforms. We found that PA-13 immunoprecipitates both the HIR-A and the HIR-B, PA-12 immunoprecipitates exclusively the HIR-B, and PA-11 fails to precipitate both isoforms. Interestingly, PA-12 inhibits specifically insulin to the HIR-B, whereas other PAs fail to affect insulin binding to either isoforms. Furthermore, PA-12 linearises the Scatchard plot of binding data, and retards the dissociation rate of insulin, thus suggesting that antibody affects cooperative interactions among binding sites. We conclude that the sequence encoded by exon 11 may play a role in modulating the binding of insulin to the receptor and negative cooperativity.


Assuntos
Éxons/genética , Insulina/metabolismo , Receptor de Insulina/genética , Células 3T3 , Sequência de Aminoácidos , Animais , Sítios de Ligação/genética , Humanos , Camundongos , Dados de Sequência Molecular , Ligação Proteica/genética , Receptor de Insulina/metabolismo , Transfecção
16.
Exp Clin Endocrinol Diabetes ; 103(1): 15-20, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7621099

RESUMO

The aim of the present study was to evaluate the effect of low dose GnRH analogue (Buserelin) on gonadal steroid secretion and hair growth in hirsute women. The drug was administered as a nasal spray (200 micrograms tid) to reduce gonadal steroid secretion. Eight hirsute women were treated for six month with the gonadotropin-releasing hormone analog. All had subclinical polycystic ovary syndromes on the basis of ultrasound or hormonal data, together with ovary dysfunctions and irregular menses. None had adrenal or pituitary dysfunction. The score of hirsutism was evaluated according to Ferriman and Gallway; pituitary function was evaluated measuring the FSH and LH response to GnRH stimulation and gonadal steroid secretion by measuring estradiol, progesterone, total plasma testosterone, androstenedione and androstanediol. Sex hormone binding globulin, insulin, prolactin and DHEA-S were also measured. The suppression of ovarian steroid secretion was confirmed by reductions in total plasma testosterone, and rostenedione and androstanediol that were detectable after one month of treatment. FSH and LH responses to GnRH stimulation were inhibited consistent with pituitary desensitization. No significant side effects were observed and all patients completed the trial. The score of hirsutism was 24 +/- 5 before, 19.6 +/- 6 by the 3rd month and 16.8 +/- 5.1 by the 6th month of treatment (p < 0.001); the effect was still evident 1 and 6 months after the withdrawal of the therapy (14.8 +/- and 15.8 +/- 5 respectively; p < 0.001). Our findings indicate that Buserelin is useful in the treatment of non adrenal hirsutism when other forms of therapy are contraindicated or poorly tolerated by the patient.


Assuntos
Busserrelina/uso terapêutico , Hirsutismo/tratamento farmacológico , Adolescente , Adulto , Androstano-3,17-diol/sangue , Androstenodiona/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Seguimentos , Hirsutismo/sangue , Humanos , Hormônio Luteinizante/sangue , Distúrbios Menstruais/fisiopatologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/fisiopatologia , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue , Fatores de Tempo
17.
J Inorg Biochem ; 23(2): 109-17, 1985 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3973582

RESUMO

Dithionite causes the depletion of dioxygen from suspensions of erythrocytes by reduction of the external dioxygen and not by diffusion into the cell. The molar enthalpy for the reduction shows a small difference with respect to the values found for free hemoglobin; and the normal stoichiometry of 2 moles dithionite/mole dioxygen found there is not observed with erythrocytes. At low hematocrit, the stoichiometry is 2.6:1 and decreases to 1.5:1 at high hematocrit. The change is not due to differences in the hemoglobin saturation or to an inability of dithionite to reduce all dioxygen present at the higher hematocrit. Neither catalase nor peroxidase added to the extracellular volume significantly alters the stoichiometry or the enthalpy of dioxygen reduction by dithionite. Addition of superoxide dismutase, however, restores the normal stoichiometry at high hematocrit and further increases the stoichiometry at low hematocrit. The calorimetrical signal of hydrogen peroxide, clearly seen with free dioxygen, is not present with erythrocytes. In all these cases the total heat evolved is the same.


Assuntos
Ditionita/farmacologia , Eritrócitos/efeitos dos fármacos , Oxiemoglobinas/metabolismo , Sulfitos/farmacologia , Animais , Calorimetria , Bovinos , Eritrócitos/metabolismo , Técnicas In Vitro , Superóxido Dismutase/farmacologia
18.
J Inorg Biochem ; 26(4): 289-94, 1986 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3711889

RESUMO

Calorimetric studies of the effect of superoxide dismutase and/or catalase on the reduction of dioxygen into water by dithionite in oxyhemoglobin have been carried out and the results compared with those in red cell hemolysates. In the absence of the enzymes the stoichiometry (moles dithionite/mole dioxygen) is less than the value of 2:1 which was found previously in red cell hemolysates [Forlani et al., J. Inorg. Biochem. 20, 147-155 (1984)]. In the presence of either superoxide dismutase or catalase alone the stoichiometry increases but is still less than 2:1. In the presence of both enzymes the stoichiometry and the shape of the thermogram is that previously observed for hemolysates, suggesting the presence of a hemoglobin-catalase-superoxide dismutase integrated system. The absence of a calorimetric signal for hydrogen peroxide in the reduction of oxyhemoglobin in the presence of superoxide dismutase suggests a wider biological role of superoxide dismutase than previously thought.


Assuntos
Catalase/sangue , Ditionita/farmacologia , Hemoglobinas/metabolismo , Oxiemoglobinas/metabolismo , Sulfitos/farmacologia , Superóxido Dismutase/sangue , Eritrócitos/enzimologia , Humanos , Cinética , Termodinâmica
20.
Acta Diabetol ; 40 Suppl 1: S263-5, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14618489

RESUMO

Morbid obesity is frequently associated with other characteristics of metabolic syndrome and is related to an increased risk of cardiovascular disease. This study aimed at evaluating time-course changes in body weight, body mass index (BMI), insulin sensitivity indexes and lipid profile in severely obese patients who underwent adjustable silicone gastric banding. We studied 19 obese subjects before and 6-36 months after surgery. An oral glucose tolerance test was performed in all non-diabetic patients. All subjects were evaluated using insulin sensitivity indexes (ISI-HOMA and QUICKI), lipid profile, and anthropometric parameters (WHR, WC, BMI), and body composition was assessed with bioelectrical impedance analysis (BIA). Most of the weight reduction occurred within the first 6-12 months, followed by near stabilisation or even weight regain. We found a significant decrease in fasting insulin, improvement in waist-hip ratio, reduction in BMI and fat mass percent. We observed an improvement in insulin sensitivity evaluated by means of ISI-HOMA and QUICKI. Bariatric surgery was an effective therapeutic approach for these obese patients because it reduced both weight and insulin resistance, along with improving metabolic parameters. Improvement in metabolic parameters appears to precede body weight reduction.


Assuntos
Índice de Massa Corporal , Balão Gástrico , Obesidade Mórbida/terapia , Adolescente , Adulto , Idoso , Área Sob a Curva , Glicemia/metabolismo , Impedância Elétrica , Feminino , Seguimentos , Balão Gástrico/efeitos adversos , Humanos , Resistência à Insulina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Aumento de Peso/fisiologia , Redução de Peso/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA