RESUMO
Glucose-dependent insulinotropic peptide (GIP) contributes to incretin effect of insulin secretion which is impaired in Type 2 diabetes mellitus. The aim of this study was to introduce a simple meal test for evaluation of GIP secretion and action and to examine GIP changes in Type 2 diabetic patients. Seventeen Type 2 diabetic patients, 10 obese non-diabetic and 17 non-obese control persons have been examined before and after 30, 60 and 90 min stimulation by meal test. Serum concentrations of insulin, C-peptide and GIP were estimated during the test. Impaired GIP secretion was found in Type 2 diabetic patients as compared with obese non-diabetic and non-obese control persons. The AUCGIP during 90 min of the meal stimulation was significantly lower in diabetic patients than in other two groups (p<0.03). Insulin concentration at 30 min was lower in diabetic than in non-diabetic persons and the GIP action was delayed. The deltaIRI/deltaGIP ratio increased during the test in diabetic patients, whereas it progressively decreased in obese and non-obese control persons. Simple meal test could demonstrate impaired GIP secretion and delayed insulin secretion in Type 2 diabetic patients as compared to obese non-diabetic and non-obese healthy control individuals.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Técnicas de Diagnóstico Endócrino , Polipeptídeo Inibidor Gástrico/metabolismo , Obesidade/diagnóstico , Obesidade/metabolismo , Adulto , Idoso , Peptídeo C/sangue , Gorduras na Dieta/farmacologia , Proteínas Alimentares/farmacologia , Sacarose Alimentar/farmacologia , Polipeptídeo Inibidor Gástrico/sangue , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/metabolismo , Insulina/sangue , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Organic hyperinsulinism causes hypoglycaemia manifesting mainly in the fasting state. We summarize our experience with diagnosis and treatment of 105 patients with organic hyperinsulinism. METHODS AND RESULTS: The diagnosis was confirmed in all patients by spontaneous hypoglycemia and neuroglycopenic symptoms, both developed during fasting test. Endoscopic ultrasonography was the most reliable method for the insulinoma localization (77% of insulinomas confirmed by surgery in the same location within the pancreas), less positive results were obtained by digital subtraction angiography (29%) and still less was found by computed tomography (18%). The localization remains unclear in about 20-25% of insulinomas despite of combined different exploring techniques. Surgical removal of insulinoma by enucleation is the best way of treatment, in some cases laparoscopic removal is a method of choice. From total number of 95 surgically treated patients the successful removal of insulinoma was performed in 84 patients (88%) and another 3 had histopathology diagnosis of micronodular polyadenomatosis. CONCLUSIONS: Insulinoma was not found during surgery and subsequent thorough histopathology investigation of the whole resecate in 8 patients which have to be treated like other non-surgically treated patients by diazoxide together with diabetic diet.
Assuntos
Hiperinsulinismo/etiologia , Insulinoma/diagnóstico , Insulinoma/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Insulinoma/complicações , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Paraoxonase 1 (PON1), an antioxidant enzyme closely associated with HDL (high-density lipoproteins), preserves LDL (low-density lipoproteins) against oxidation. Less protection may be therefore supposed by decreased PON1 activity. This study was undertaken to investigate the association of PON1 gene polymorphisms with diabetic angiopathy and to evaluate the relationship of these polymorphisms with PON1 activity. Total of 86 Type 1 (T1DM) and 246 Type 2 (T2DM) diabetic patients together with 110 healthy subjects were examined. DNA isolated from leukocytes was amplified with polymerase chain reaction (PCR) followed by restriction enzyme digestion. The products were analyzed for L55M and Q192R polymorphisms in coding region and for -107 C/T and -907 G/C in promotor sequence of PON1. Serum enzyme activity was measured spectrophotometrically. Significant differences were found between T1DM or T2DM and control persons in L55M polymorphism (allele M more frequent in T1DM and T2DM vs. controls, p<0.05) and Q192R polymorphism (R allele less frequent in T1DM and T2DM vs. controls, p<0.01) of the PON1 gene. Serum PON1 activity was significantly decreased in T1DM (110+/-68 nmol/ml/min) and T2DM patients (118+/-69 nmol/ml/min) compared to the control persons (203+/-58 nmol/ml/min), both p<0.01. The presence of MM and QQ genotypes was accompanied by lower PON1 activity than of LL and RR genotypes (p<0.05), respectively. Better diabetes control was found in patients with LL than with MM genotypes and similarly in RR genotype than QQ genotype with p<0.05. Significantly different allele frequencies were found in diabetic patients with macroangiopathy than in those without it (M: 0.59 vs. 0.44. R: 0.12 vs. 0.19, p<0.01). The association of PON1 polymorphisms, lower PON1 activity and poorer diabetes control found in patients with macroangiopathy further support the idea of genetic factors contributing to the development of vascular disorders in diabetes.
Assuntos
Arildialquilfosfatase/genética , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Arildialquilfosfatase/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/enzimologia , Angiopatias Diabéticas/enzimologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fases de Leitura Aberta , Fenótipo , Regiões Promotoras GenéticasRESUMO
Polyunsaturated fatty acids of n-3 series (n-3 PUFA) were shown to increase basal fat oxidation in humans. The aim of the study was to compare the effect of n-3 PUFA added to a very low calorie diet (VLCD), with VLCD only during three-week inpatient weight reduction. Twenty severely obese women were randomly assigned to VLCD with n-3 PUFA or with placebo. Fatty acids in serum lipid fractions were quantified by gas chromatography. Differences between the groups were determined using ANOVA. Higher weight (7.55+/-1.77 vs. 6.07+/-2.16 kg, NS), BMI (2.82+/-0.62 vs. 2.22+/-0.74, p<0.05) and hip circumference losses (4.8+/-1.81 vs. 2.5+/-2.51 cm, p<0.05) were found in the n-3 group as compared to the control group. Significantly higher increase in beta-hydroxybutyrate was found in the n-3 group showing higher ketogenesis and possible higher fatty acid oxidation. The increase in beta-hydroxybutyrate significantly correlated with the increase in serum phospholipid arachidonic acid (20:4n-6; r = 0.91, p<0.001). In the n-3 group significantly higher increase was found in n-3 PUFA (eicosapentaenoic acid, 20:5n-3, docosahexaenoic acid, 22:6n-3) in triglycerides and phospholipids. The significant decrease of palmitoleic acid (16:1n-7) and vaccenic acid (18:1n-7) in triglycerides probably reflected lower lipogenesis. A significant negative correlation between BMI change and phospholipid docosahexaenoic acid change was found (r = -0.595, p<0.008). The results suggest that long chain n-3 PUFA enhance weight loss in obese females treated by VLCD. Docosahexaenoate (22:6n-3) seems to be the active component.
Assuntos
Dieta Redutora , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Obesidade/dietoterapia , Redução de Peso , Ácido 3-Hidroxibutírico/sangue , Restrição Calórica , Ácidos Docosa-Hexaenoicos/análise , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/análise , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos Monoinsaturados/análise , Ácidos Graxos Ômega-3/análise , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Ácidos Oleicos/análise , Fosfolipídeos/sangue , Triglicerídeos/sangueRESUMO
Oxidative stress is higher in obese diabetic than in non-diabetic subjects. This pilot study evaluates oxidative stress during short-term administration of a very low calorie diet in obese persons. Nine obese Type 2 diabetic patients (age 55+/-5 years, BMI 35.9+/-1.9 kg/m2) and nine obese non-diabetic control subjects (age 52+/-6 years, BMI 37.3+/-2.1 kg/m2) were treated by a very low calorie diet (600 kcal daily) during 8 days stay in the hospital. Serum cholesterol, triglycerides, non-esterified fatty acids (NEFA), beta-hydroxybutyrate (B-HB), ascorbic acid (AA), alpha-tocopherol (AT), plasma malondialdehyde (MDA) and superoxide dismutase (SOD) activity in erythrocytes were measured before and on day 3 and 8 of very low calorie diet administration. A decrease of serum cholesterol and triglyceride concentrations on day 8 was associated with a significant increase of NEFA (0.30+/-0.13 vs. 0.47+/-0.11 micromol/l, p<0.001) and B-HB (0.36+/-.13 vs. 2.23+/-1.00 mmol/l, p<0.001) in controls but only of B-HB (1.11+/-0.72 vs. 3.02+/-1.95 mmol/l, p<0.001) in diabetic patients. A significant decrease of plasma MDA and serum AT together with an increase of SOD activity and AA concentration (p<0.01) was observed in control persons, whereas an increase of SOD activity (p<0.01) was only found in diabetic patients after one week of the very low calorie diet. There was a significant correlation between NEFA or B-HB and SOD activity (p<0.01). We conclude that one week of a very low calorie diet administration decreases oxidative stress in obese non-diabetic but only partly in diabetic persons. Diabetes mellitus causes a greater resistance to the effects of a low calorie diet on oxidative stress.
Assuntos
Restrição Calórica , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/dietoterapia , Obesidade/metabolismo , Estresse Oxidativo , Adulto , Idoso , Ácido Ascórbico/sangue , Biomarcadores , Feminino , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Projetos Piloto , Superóxido Dismutase/sangue , alfa-Tocoferol/sangueRESUMO
As an autoimmune disease, type 1 diabetes mellitus (DM) can be associated with other autoimmune disorders. The aim of this study was to detect subclinically associated autoimmune thyroid disease, coeliac disease, and Addison's disease. The presence of autoantibodies was evaluated with special regard to the control of diabetes and to the clinical status of the patient. Fifty-one type 1 diabetic patients (22 men, 29 women, mean age 37+/-11 years, mean duration of diabetes 16+/-13 years) were included into this study. Specific antibodies to islet antigens--glutamic acid decarboxylase (GAD65), protein thyrosine phosphatase IA-2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by RIA. Autoantigens of the small intestine--tissue transglutaminase autoantibodies (ATTG), IgA and IgG antibodies to gliadin (AGA-IgA, AGA-IgG) were evaluated by ELISA. Endomysial autoantibodies (EMA) and adrenal cortex antibodies (ACA) were detected by indirect immunofluorescence microscopy. Eleven new cases of thyreopathy (22 % of patients) were detected by the assessment of thyroid autoantibodies and TSH. Two new cases of thyreotoxicosis were diagnosed during the study. Coeliac disease was diagnosed in at least two cases. Addison's disease was not diagnosed, although the ACA were positive in two patients. No influence of single or combined autoantibody positivity on the control of diabetes was found if normal organ function was preserved. In both patients with thyreotoxicosis the control of diabetes was worsened and improved after treatment. The screening of autoantibodies in type 1 diabetic patients could reveal subclinical cases of AITD or coeliac disease. Subclinical forms of these disorders have no influence on diabetes control. However, impaired organ function may be associated with the worsened control of diabetes as we demonstrated on two newly diagnosed cases of thyreotoxicosis. We suggest the need for the follow-up of patients with positive autoantibodies because further deterioration of the respective organs can be expected.
Assuntos
Doença de Addison/imunologia , Autoimunidade , Doença Celíaca/imunologia , Diabetes Mellitus Tipo 1/imunologia , Tireoidite Autoimune/imunologia , Doença de Addison/complicações , Córtex Suprarrenal/imunologia , Adulto , Autoanticorpos/sangue , Doença Celíaca/complicações , Diabetes Mellitus Tipo 1/complicações , Feminino , Gliadina/imunologia , Glutamato Descarboxilase/imunologia , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Isoenzimas/imunologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Tireoidite Autoimune/complicações , Transglutaminases/imunologiaRESUMO
The influence of either short-term fasting or vitamin E administration on insulin action was studied in two groups of obese Type 2 diabetic patients. Twelve patients underwent 7 days of fasting (group A), whereas 600 mg of vitamin E was administered daily during 3 months in 9 diabetic patients (group B). Insulin action was examined by using hyperinsulinemic isoglycemic clamps (insulin infusion rate, 1.0 mU/kg/min) and insulin receptors on erythrocytes before and after respective regimens. An increase of glucose disposal rate (29.5 +/- 8.9 vs. 24.0 +/- 7.5 mumol/kg/min, p < 0.01) and an increase of metabolic clearance rate of glucose (4.0 +/- 2.5 vs. 2.3 +/- 0.9 mL/kg/min, p < 0.01) were observed in group A after fasting. On the contrary, decreases of glucose disposal rate (21.3 +/- 8.5 vs. 26.6 +/- 9.8 mumol/kg/min, p < 0.02), metabolic clearance rate of glucose (2.9 +/- 0.8 vs. 3.7 +/- 1.7 mL/kg/min, p < 0.05), and insulin receptor number (p < 0.01) were found after vitamin E administration as compared with pretreated values. A worsening of diabetes control as observed by an increase of HbA1C (p < 0.01) was present in the latter group. In summary, we found an improvement of insulin action after short-term fasting in contrast with the worsening of metabolic parameters after vitamin E administration in obese Type 2 diabetic patients.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Jejum , Insulina/metabolismo , Obesidade/metabolismo , Vitamina E/administração & dosagem , Administração Oral , Adulto , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Receptor de Insulina/metabolismoRESUMO
Serum N-acetyl-beta-glucosaminidase activity was evaluated in 40 Type 1 and 40 Type 2 diabetic patients and compared with parameters of diabetes control and oxidative stress. Significantly increased mean serum N-acetyl-beta-glucosaminidase activity was found in both groups of diabetic patients as compared with the corresponding group of healthy persons (p < 0.01). Oxidative stress measured by plasma malondialdehyde concentration was significantly higher in Type 2 than in Type 1 diabetic patients (p < 0.01) but in comparison with control subjects it was higher only in Type 2 diabetes. Plasma malondialdehyde concentration positively correlated with body mass index (r=0.77, p<0.001) and with serum N-acetyl-beta-glucosaminidase activities (r=0.57, p <0.001). Treatment of 10 Type 2 diabetic patients with antioxidant alpha-tocopherol caused a significant decrease in malondialdehyde concentration (p < 0.001) which was accompanied by a decrease of N-acetyl-beta-glucosaminidase activity (p < 0.01). We conclude that serum N-acetyl-beta-glucosaminidase activity may be influenced by oxidative stress which is more pronounced in Type 2 than in Type 1 diabetic patients.
Assuntos
Acetilglucosaminidase/sangue , Diabetes Mellitus/enzimologia , Estresse Oxidativo , Adulto , Índice de Massa Corporal , Diabetes Mellitus/sangue , Humanos , Malondialdeído/sangue , Pessoa de Meia-Idade , Superóxido Dismutase/sangueRESUMO
A modification of the enzymic method of Tabor and Wyngarden for formiminoglutamate (FIGLU) estimation in urine is described. Alkaline degradation of FIGLU in blanks enhanced the sensitivity of the method. FIGLU excretion in 94 healthy persons indicated a sex and age dependence. Short term calorie restriction or fasting led to a decrease of FIGLU excretion while acute alcohol intoxication or chronic alcohol administration were accompanied by enhanced FIGLU excretion. It is suggested that decreased FIGLU excretion was due to histidine deficiency.
Assuntos
Intoxicação Alcoólica , Dieta , Ingestão de Energia , Ácido Formiminoglutâmico/urina , Glutaratos/urina , Adulto , Fatores Etários , Idoso , Alcoolismo/urina , Teste de FIGLU/métodos , Jejum , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores SexuaisRESUMO
The relationship between specific insulin binding to insulin receptors on erythrocytes and erythrocyte membrane phospholipid fatty acid pattern was evaluated in 11 healthy men. A significant negative correlation between insulin binding and the proportion of w-6 family essential fatty acids, especially linoleic acid (r = -0.82, p less than 0.01) and arachidonic acid (r = -0.73, p less than 0.05) in erythrocyte membrane was found. On the other hand significant positive correlation between insulin binding and the content of nonessential fatty acids (r = +0.65, p less than 0.05) was seen. Data presented support the hypothesis that the fatty acid composition of membrane phospholipids may modify properties of insulin receptors.
Assuntos
Membrana Eritrocítica/análise , Eritrócitos/metabolismo , Ácidos Graxos/sangue , Insulina/metabolismo , Lipídeos de Membrana/sangue , Fosfolipídeos/sangue , Adulto , Ácidos Araquidônicos/sangue , Humanos , Ácidos Linoleicos/sangue , Masculino , Pessoa de Meia-Idade , Receptor de Insulina/fisiologiaRESUMO
Biochemical markers of early changes that are characteristic for diabetic microangiopathy are not completely understood. We investigated activities of serum N-acetyl-beta-glucosaminidase (NAG), tissue plasminogen activator and erythrocyte superoxide dismutase in well defined groups of type 1 diabetic patients. Patients were selected on the basis of 4 year follow-up observation. Forty-two type 1 diabetic patients were subdivided into those without retinopathy (n = 13) throughout the study, those with newly developed or worsened retinopathy (n = 12) during 4 years and those with retinopathy already established at the beginning of the study and without evidence of its progression (n = 17). All diabetic patients had albustix-negative urine. A significant increase of the mean serum NAG activity during 4 years was found only in patients without retinopathy (P < 0.01) whereas no changes of the altered enzyme activities were present in patients with developing and established retinopathy. The mean activity of tissue plasminogen activator was elevated in all groups of diabetic patients compared with healthy subjects (P < 0.001). A significant positive correlation was found between plasminogen activator and serum NAG (r = 0.51, P < 0.01). Erythrocyte superoxide dismutase was higher in diabetic patients than in healthy persons (P < 0.01) but no differences were observed between the patients with or without retinopathy. Superoxide dismutase positively correlated with NAG (r = 0.57, P < 0.01). We conclude that early functional changes precede a morphological development of diabetic retinopathy as was evident from the altered enzyme activities.
Assuntos
Acetilglucosaminidase/sangue , Diabetes Mellitus Tipo 1/enzimologia , Retinopatia Diabética/enzimologia , Eritrócitos/enzimologia , Superóxido Dismutase/sangue , Ativador de Plasminogênio Tecidual/sangue , Adulto , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Increased oxidative stress, hypofibrinolysis and insulin resistance are present in obese Type 2 diabetic patients. It is supposed that treatment with antioxidant alpha-tocopherol (vitamin E) could not only decrease free radical production, but also ameliorate insulin action. We evaluated the effect of 3 months administration of vitamin E (600 mg daily) on insulin action examined by hyperinsulinemic clamp in 11 obese Type 2 diabetic patients. Oxidative stress and fibrinolysis were also determined. The administration of vitamin E caused a decrease of glucose disposal rate (26.6 +/- 9.5 vs 21.3 +/- 7.5 micromol/kg/min, P < 0.02) and of metabolic clearance rate of glucose (3.7 +/- 1.6 vs 2.9 +/- 0.8 ml/kg/min. P < 0.02). A decrease of insulin receptor number was observed on erythrocytes after vitamin E (284 +/- 84 vs 171 +/- 59 pmol/l, P < 0.01). Significantly higher plasma malondialdehyde (MDA) concentration documented an increased oxidative stress in diabetic patients as compared with healthy persons (3.13 +/- 0.68 vs 1.89 +/- 0.18 micromol/l, P<0.001). An inverse relationship was found between MDA concentration and insulin sensitivity expressed by glucose disposal rate (r = -0.73). Vitamin E further worsened the hypofibrinolysis documented by a decrease of tissue plasminogen activator (P < 0.01) without changes in its inhibitor PAI-1. In conclusion. our results demonstrate that higher doses of vitamin E may further deteriorate insulin action and fibrinolysis in obese Type 2 diabetic patients.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/fisiopatologia , Fibrinólise/fisiologia , Insulina/farmacologia , Obesidade , Vitamina E/uso terapêutico , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea , Diabetes Mellitus/sangue , Diabetes Mellitus Tipo 2/sangue , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Fibrinólise/efeitos dos fármacos , Técnica Clamp de Glucose , Humanos , Infusões Intravenosas , Insulina/administração & dosagem , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estresse Oxidativo , Inibidor 1 de Ativador de Plasminogênio/sangue , Receptor de Insulina/sangue , Valores de Referência , Ativador de Plasminogênio Tecidual/sangueRESUMO
The relationship between arterial hypertension and insulin resistance has long been established. We used primary hyperaldosteronism as a model of the relationship between secondary hypertension and insulin sensitivity. Our group consisted of 9 patients with arterial hypertension caused by primary hyperaldosteronism. Five of these patients with aldosterone producing adenoma were operated on and four patients with idiopathic hyperaldosteronism were treated with spironolactone. Hyperinsulinaemic euglycaemic clamp technique was performed before and at least 6 months following the treatment to evaluate the insulin action. Significantly lower glucose disposal rate (M), insulin sensitivity index (M/I) and decreased metabolic clearance rate of glucose (MCR(G)) were found in patients before treatment as compared to healthy controls. In both treated groups the blood pressure and plasma potassium concentrations returned to normal values, whereas plasma aldosterone levels were normalised only after surgical removal of the adenoma. Significantly improved insulin action (M/I: 30.2 +/- 5.9 vs. 51.4 +/-12.2 micromol.kg(-1).min(-1) per mU.l(-1) x 100, p = 0.017) was observed in patients after operation of aldosterone producing adenoma. In contrast, spironolactone treatment of patients with idiopathic hyperaldosteronism did not significantly influence insulin action (M/I: 24.5 +/- 7.3 vs. 18.7 +/- 7.6 micromol.kg(-1).min(-1) per mU.l(-1) x 100, p = 0.198). Since plasma aldosterone concentrations have been normalised only in patients after removal of the adenoma whereas they remained increased in spironolactone treated group, we suppose that aldosterone itself could play a role in the development of impaired insulin action.
Assuntos
Hiperaldosteronismo/complicações , Hipertensão/fisiopatologia , Insulina/farmacologia , Adenoma/complicações , Adenoma/metabolismo , Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Aldosterona/biossíntese , Aldosterona/sangue , Glicemia/metabolismo , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Humanos , Hiperaldosteronismo/fisiopatologia , Hiperaldosteronismo/terapia , Hipertensão/etiologia , Resistência à Insulina , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Potássio/sangue , Renina/sangue , Espironolactona/uso terapêuticoRESUMO
Glucose tolerance, insulin binding to erythrocytes, insulinaemia, plasma total cholesterol, plasma triglycerides, weight of fat pads, food consumption and body weight changes were studied in genetically hypertensive lean Koletsky rats. Long-term treatment with dopaminergic agonist terguride (0.2 mg/kg/day) normalized glucose tolerance and increased the percentage of bound insulin to erythrocytes in both sexes. Terguride decreased insulinaemia, cholesterolaemia, fat pads and body weight only in female rats. Food consumption was not influenced by terguride over the injection period.
Assuntos
Agonistas de Dopamina/farmacologia , Hiperlipidemias/fisiopatologia , Insulina/sangue , Lisurida/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Teste de Tolerância a Glucose , Hiperlipidemias/sangue , Lisurida/farmacologia , Masculino , Ratos , Ratos Endogâmicos SHRRESUMO
The presence of insulin resistance is frequently found in essential hypertension. There are, however, only sparse data with respect to the potential presence of insulin resistance in patients with secondary hypertension. We have therefore undertaken a study to reveal the potential occurrence of insulin resistance in primary hyperaldosteronism (PH). The hyperinsulinemic euglycemic clamp technique together with the evaluation of insulin receptor characteristics were used to study insulin resistance in 12 patients with PH. The measured parameters were compared to normal values in control subjects. We have found a significantly lower glucose disposal rate (M, micromol/kg/min) (18.7+/-6 vs. 29.3+/-4), decreased tissue insulin sensitivity index (M/I, micromol/kg/min per mU/l x100) (23.7+/-9.8 vs. 37.5+/-11.6) and also lower metabolic clearance rate of glucose (MCRg, ml/kg/min) (3.8+/-1.5 vs. 7.0+/-1.1) in patients with primary hyperaldosteronism. The insulin receptor characteristics on erythrocytes did not differ in primary hyperaldosteronism as compared to control healthy subjects. We thus conclude that insulin resistance is also present in secondary forms of hypertension (primary hyperaldosteronism) which indicates the heterogeneity of impaired insulin action in patients with arterial hypertension.
Assuntos
Hiperaldosteronismo/fisiopatologia , Resistência à Insulina , Adulto , Glicemia/análise , Eritrócitos/metabolismo , Glucose/metabolismo , Técnica Clamp de Glucose , Humanos , Pessoa de Meia-Idade , Receptor de Insulina/sangue , Valores de ReferênciaRESUMO
Androgen receptors were found both in cytosol prepared from intact thymuses of the adult castrated B10. A male and in cytosol from thymuses of the castrated males that had been previously given whole-body irradiation with 6.0 Gy (60Co). Histologically, these thymuses were represented by the reticuloepithelial component, no lymphocytes were found in the cortex and small numbers of lymphocytes remained in the medulla. The 3H-dihydrotestosterone-receptor complex sedimented in the 4S region, as revealed by the 5-20% sucrose gradient centrifugation in buffer containing 0.4 M KC1. Free androgen and non-specifically bound androgen were removed by specific antibody coupled to CNBr-activated Sepharose-4B.
Assuntos
Receptores Androgênicos/análise , Receptores de Esteroides/análise , Timo/análise , Animais , Epitélio/análise , Linfócitos/análise , Masculino , Camundongos , Camundongos Endogâmicos , Reticulócitos/análiseRESUMO
Experiments were carried out in the genetically hypertensive obese rats of Koletsky type (SHR/N-cp) and in their lean siblings. Regression analysis was performed when plasma triglycerides was used as a dependent variable and plasma insulin, insulin binding to erythrocytes, basal plasma glucose tolerance data were used as independent variables. Coefficient determination (R2) as well as the tests of hypotheses of regression coefficients being zero were used to indicate which independent variables contributed the least in the explanation of dependent variable. This way we reduced the list of variables to give a simpler regression equation. In the control animals insulinemia was found to be dominant independent variable in all groups except SHR/N-cp obese females where the dominant independent variable was represented by the basal plasma glycaemia. Under the terguride treatment only in SHR/N-cp female rats the dominant independent variable remained the same as in controls. In the other groups the dominant independent variable was different in relation to the control animals. Long lasting terguride treatment normalized hypertriglyceridemia only in SHR/N-cp obese females. Thus the data obtained by multiple regression analysis of parameters of lipide and glycide metabolism show the close relationship to alleviating effect of terguride in hypertriglyceridemia.
Assuntos
Agonistas de Dopamina/farmacologia , Glucose/metabolismo , Hipertensão/metabolismo , Lisurida/análogos & derivados , Obesidade/metabolismo , Triglicerídeos/sangue , Animais , Feminino , Teste de Tolerância a Glucose , Hipertensão/complicações , Insulina/sangue , Lisurida/farmacologia , Masculino , Obesidade/complicações , Ratos , Ratos Endogâmicos SHR , Análise de RegressãoRESUMO
Experiments were performed in the genetically hypertensive lean males of Koletsky type. It was monitored the effect of dehydroepiandrosterone (DHEA) treatment on lipemia, glucose tolerance, insulinemia, insulin binding to erythrocytes, fat pads, body weight and pellet intake. DHEA was applied in two doses: 10 and 20 mg per kg b.w., i.p., for 11 days when glucose tolerance was monitored and for 21 days when the remaining parameters were analyzed. DHEA shows dose dependent decrease in changes of body weight over injection period, in plasma triglycerides and total plasma cholesterol, decrease being most expressed under the higher dose. High as well low of DHEA decreases the sum of glycaemia obtained 30, 60, 120 and 180 min after glucose loading (area under the curve) i.e., DHEA alleviates genetically based glucose intolerance. DHEA induced hypophagia under the higher dose treatment. Insulin binding to erythrocytes was not influenced by DHEA.
Assuntos
Desidroepiandrosterona/farmacologia , Eritrócitos/metabolismo , Teste de Tolerância a Glucose , Insulina/sangue , Lipídeos/sangue , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Endogâmicos SHRRESUMO
Two series of experiments were performed. In the first one experiments were carried out in Koletsky genetically hypertensive lean female rats and in the normotensive female rats of Wistar strain. Glucose intolerance was induced by oligemic brain hypoxia (4 hours of occlusion of both common carotid arteries followed by 44 hours reperfusion). Brain water content were used as a marker of brain edema. Changes in insulinemia and specific insulin binding were used as expression of regulative mechanisms participating in modification of glucose tolerance. The effect of terguride (trans-dihydro-lisuride) was tested. Brain hypoxia induced glucose intolerance in both strains of rat but brain edema was found only in the normotensive females. Both abnormalities were alleviated by terguride treatment. Basal glycaemia was not changed either by the brain hypoxia or by terguride treatment, except normotensive female where brain hypoxia induced hyperglycaemia. The second series of experiments were carried out in the normotensive females. The arrangement of experiments was the same as in first series except omission of the final glucose tolerance test. Brain hypoxia causes increase in brain water content. The mentioned elevation of brain water content was alleviated by terguride treatment. Insulin binding to erythrocytes was not influenced by brain hypoxia. Terguride treatment shows decrease of insulin binding to erythrocytes. Brain hypoxia elevates insulinemia which was not alleviated by terguride treatment.
Assuntos
Agonistas de Dopamina/uso terapêutico , Intolerância à Glucose/tratamento farmacológico , Hipóxia Encefálica/tratamento farmacológico , Lisurida/análogos & derivados , Animais , Glicemia/metabolismo , Água Corporal/metabolismo , Química Encefálica , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Feminino , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Hipóxia Encefálica/complicações , Hipóxia Encefálica/metabolismo , Insulina/sangue , Lisurida/uso terapêutico , Ratos , Ratos Endogâmicos SHR , Ratos WistarRESUMO
Experiments were performed in the genetically hypertensive obese rats of Koletsky type (SHR/N-cp) and in their lean siblings. The effect of long lasting terguride treatment on glycide and lipid metabolism was monitored. Terguride decreases insulinemia in all groups of rats. In all groups of rats terguride increases tolerance glucose. Terguride increases insulin binding to erythrocytes in all groups of rats except SHR/N-cp obese females. The mentioned drug decreases plasma triglycerides in SHR/N-cp obese females. On the other hand, this drug increases plasma triglycerides in SHR/N-cp obese males. Correlation between basal glycemia and insulin binding to erythrocytes as well as between triglycerides and insulinemia which was found in control SHR/N-cp lean males is missing under the terguride treatment. Similarly, correlation between plasma triglycerides and insulinemia, glucose tolerance and insulinemia, basal glycemia and insulinemia, plasma triglycerides and basal glycemia are missing under the terguride treatment in SHR/N-cp lean females. Under the terguride treatment there appears correlation between insulin binding to erythrocytes and basal glycemia. We found in SHR/N-cp obese males opposite changes in number of correlations when we compare control and terguride animals. While in controls only one correlation was detected, i.e., correlation between glucose tolerance and insulin binding to erythrocytes, then under the terguride treatment there appear correlations when basal glycemia is computed versus insulin binding to erythrocytes or to glucose tolerance and/or to triglycerides. Moreover, there is under the terguride treatment correlation insulin binding to erythrocytes versus plasma triglycerides or versus insulinemia. While in SHR/N-cp lean of both sexes and in SHR/N-cp obese males profound changes in the number of statistically significant correlation coefficients were found when controls are compared with animals under the terguride treatment, the different picture we found in SHR/N-cp obese females, i.e., under the terguride treatment correlation basal glycemia versus insulinemia or versus insulin binding to erythrocytes as well as correlation insulin binding to erythrocytes versus insulinemia is present in controls as well as in terguride treated animals. In comparison with controls under terguride only two correlations are missing, i.e., glucose tolerance versus insulinemia or versus insulin binding to erythrocytes.