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1.
Rinsho Shinkeigaku ; 57(12): 759-763, 2017 Dec 27.
Artigo em Japonês | MEDLINE | ID: mdl-29187686

RESUMO

We describe the case of a 90-year-old woman who was hospitalized in July 2016 and subsequently experienced a sudden decline in consciousness level resulting in a state of deep coma. Involuntary movements were not observed, and bilateral Babinski signs were inconclusive. Diffusion-weighted MRI (DWI) of the brain showed bilateral hyperintensity in the thalamus and internal capsule, laboratory testing detected high levels of plasma ammonia, and an electroencephalogram showed delta waves and triphasic waves predominantly in the frontal lobe. Based on these results, treatment for hepatic encephalopathy was administered, which led to an improvement in consciousness level, a decrease in plasma ammonia levels, and a normalization in the DWI scan. Abdominal computed tomography scan showed no abnormality in the liver, but revealed an abnormal blood vessel leading from the ileocolic vein to the inferior vena cava; the patient was diagnosed with portal-systemic encephalopathy. In deep coma patients, acute encephalopathy with hyperammonemia is important for differential diagnosis when DWI shows high-density legions in the thalamus and internal capsule.


Assuntos
Imagem de Difusão por Ressonância Magnética , Encefalopatia Hepática/diagnóstico por imagem , Cápsula Interna/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Eletroencefalografia , Feminino , Encefalopatia Hepática/complicações , Humanos , Hiperamonemia/etiologia , Tomografia Computadorizada por Raios X
2.
Diabetes Res Clin Pract ; 109(2): e8-e10, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26025695

RESUMO

We describe a type 2 diabetes patient with persistent hypoglycemia caused by sulfonylurea misuse on top of a DPP-4 inhibitor. Hyperinsulinemia was exaggerated by dextrose administration, but was successfully treated with octreotide. Since many patients are currently treated with DPP-4 inhibitors, the importance of octreotide has been increasing. For refractory sulfonylurea-induced hypoglycemia, especially when the patient is also being given an incretin-based therapy, octreotide should be considered.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Hipoglicemia/tratamento farmacológico , Octreotida/uso terapêutico , Compostos de Sulfonilureia/efeitos adversos , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores Enzimáticos/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Masculino , Compostos de Sulfonilureia/uso terapêutico
3.
Endocr J ; 62(2): 133-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25328079

RESUMO

This study aimed to explore the effects of the dipeptidyl peptidase-4 inhibitor sitagliptin and the biguanide metformin on the secretion of insulin and glucagon, as well as incretin levels, in Japanese subjects with type 2 diabetes mellitus poorly controlled with insulin monotherapy. This was a single-center, randomized, open-label, parallel group study, enrolling 25 subjects. Eleven patients (hemoglobin A1c [HbA1c] 8.40 ± 0.96%) and 10 patients (8.10 ± 0.54%) on insulin monotherapy completed 12-week treatment with sitagliptin (50 mg) and metformin (750 mg), respectively. Before and after treatment, each subject underwent a meal tolerance test. The plasma glucose, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), C-peptide, and glucagon responses to a meal challenge were measured. HbA1c reductions were similar in patients treated with sitagliptin (0.76 ± 0.18%) and metformin (0.77 ± 0.17%). In the sitagliptin group, glucose excursion during a meal tolerance test was reduced and accompanied by elevations in active GLP-1 and active GIP concentrations. C-peptide levels were unaltered despite reduced glucose responses, while glucagon responses were significantly suppressed (-7.93 ± 1.95% of baseline). In the metformin group, glucose excursion and incretin responses were unaltered. C-peptide levels were slightly increased but glucagon responses were unchanged. Our data indicate that sitagliptin and metformin exert different effects on islet hormone secretion in Japanese type 2 diabetic patients on insulin monotherapy. A glucagon suppressing effect of sitagliptin could be one of the factors improving blood glucose control in patients inadequately controlled with insulin therapy.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Células Secretoras de Glucagon/efeitos dos fármacos , Glucagon/antagonistas & inibidores , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Fosfato de Sitagliptina/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Polipeptídeo Inibidor Gástrico/agonistas , Polipeptídeo Inibidor Gástrico/sangue , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/agonistas , Peptídeo 1 Semelhante ao Glucagon/sangue , Células Secretoras de Glucagon/metabolismo , Hemoglobinas Glicadas/análise , Humanos , Insulina/metabolismo , Insulina/uso terapêutico , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Período Pós-Prandial
4.
Heart Vessels ; 28(2): 157-65, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22457095

RESUMO

Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = -0.24, P < 0.05; r = -0.17, P < 0.05, r = -0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.


Assuntos
Bilirrubina/sangue , Proteína C-Reativa/análise , HDL-Colesterol/sangue , Circulação Coronária , Doença das Coronárias/sangue , Vasos Coronários/metabolismo , Endotélio Vascular/metabolismo , Mediadores da Inflamação/sangue , Idoso , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Glicemia/análise , Distribuição de Qui-Quadrado , Angiografia Coronária , Doença das Coronárias/diagnóstico , Doença das Coronárias/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Estudos Transversais , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Fluxometria por Laser-Doppler , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estresse Oxidativo , Valor Preditivo dos Testes , Ultrassonografia , Vasodilatadores
5.
J Atheroscler Thromb ; 18(5): 403-12, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21350306

RESUMO

AIM: Bilirubin has antioxidant properties and may protect against atherosclerosis and coronary heart disease (CHD). Further, in patients with metabolic syndrome, hyperbilirubinemia is associated with attenuation of insulin resistance. The aim of the present study was to determine the relationship between serum bilirubin concentration and coronary endothelial function in overweight patients. METHODS: The study population consisted of 107 patients without CHD who underwent coronary flow studies. Vascular reactivity was examined by intra-coronary administration of papaverine and nitroglycerin. Coronary endothelial function was evaluated by assessing the change in coronary artery diameter to papaverine [percent change in flow-mediated dilatation (%FMD)] and nitroglycerin (%NTG). Serum total bilirubin, high-sensitivity C-reactive protein (hs-CRP), high density lipoprotein-cholesterol (HDL-C), fasting plasma glucose and immunoreactive insulin levels were also measured, and the homeostasis model assessment insulin resistance (HOMA-IR) index was calculated. Patients were divided into two groups according to body mass index (BMI): an overweight group (BMI ≥ 25; n = 36) and a normal weight group (BMI < 25; n = 71). RESULTS: In the overweight group, univariate analysis revealed that log-transformed total bilirubin was positively correlated with %FMD and HDL-C (r = 0.38, p< 0.05; r = 0.30, p < 0.05, respectively) and was inversely correlated with log-transformed hs-CRP and HOMA-IR (r = -0.45, p < 0.01; r = -0.45, p< 0.05, respectively). Multivariate analysis revealed that log-transformed hs-CRP was the only independent predictor of log-transformed total bilirubin (p< 0.05). CONCLUSIONS: These results suggest that a high bilirubin level was associated with favorable coronary endothelial function in overweight patients. Further, the anti-inflammatory effects of bilirubin may mediate this effect.


Assuntos
Bilirrubina/sangue , Vasos Coronários/patologia , Endotélio Vascular/patologia , Inflamação/etiologia , Inflamação/patologia , Sobrepeso/complicações , Idoso , Feminino , Humanos , Masculino , Fatores de Risco
6.
Endocr J ; 57(7): 639-44, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20431231

RESUMO

The insulin-induced hypoglycemia test (insulin tolerance test: ITT) and corticotropin-releasing hormone (CRH) test are used to examine the activities of the hypothalamo-pituitary-adrenal (HPA) axis. Growth hormone-releasing peptide-2 (GHRP-2), a potent GH secretagogue, also stimulates adrenocorticotropin (ACTH) secretion. To evaluate the role of GHRP-2 in assessing the HPA axis, we examined 6 patients with various hypothalamo-pituitary disorders, and measured ACTH and cortisol responses during provocative tests (ITT, CRH, and GHRP-2 test). None of the 6 patients showed any significant ACTH or cortisol responses to ITT, but significant ACTH release was observed during CRH and GHRP-2 tests. These findings suggest GHRP-2 may directly stimulate ACTH secretion in patients with hypothalamo-pituitary disorders.


Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Hipoglicemia/induzido quimicamente , Doenças Hipotalâmicas/metabolismo , Insulina/farmacologia , Oligopeptídeos/farmacologia , Testes de Função do Córtex Suprarrenal , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/metabolismo , Doenças Hipotalâmicas/sangue , Masculino , Pessoa de Meia-Idade
7.
J Atheroscler Thromb ; 17(3): 259-69, 2010 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-20228613

RESUMO

AIM: The aim of this study was to investigate the role of uric acid (UA) in coronary endothelial function via its effects on renal function, other coronary risk factors and asymmetric dimethylarginine (ADMA) in men and women. METHODS: The study population consisted of 194 consecutive patients (119 men and 75 women) without coronary artery disease. The relationships between UA and coronary endothelial function, estimated glomerular filtration rate (eGFR), ADMA or other biochemical or anthropometric parameters were investigated. RESULTS: Monovariate analysis of female participants demonstrated that % change in coronary blood flow (CBF) induced by acetylcholine (ACh) was inversely correlated with UA, ADMA and age (r=-0.32, p<0.01; r=-0.31, p<0.05; r=-0.23, p<0.05, respectively), and positively correlated with eGFR (r=0.27, p<0.05). Stepwise regression analysis showed that UA was the only independent predictor of % change in CBF induced by ACh (F value 4.969, p<0.05). Similar analysis of male participants failed to show significant correlations of these variables except for age in monovariate analysis (r=-0.19, p<0.05). Meanwhile, UA was inversely correlated with eGFR in both men and in women (r=-0.25, p<0.01; r=-0.59, p<0.0001, respectively), and ADMA was positively correlated with UA and inversely correlated with eGFR (r=0.36, p<0.05; r=-0.42, p<0.01, respectively) in women but not in men. CONCLUSION: High concentrations of UA correlate with coronary endothelial microvascular dysfunction in women. Further, serum UA concentration is related to eGFR and ADMA only in women, which may result in impaired endothelial function in resistance coronary arteries in women but not in men.


Assuntos
Arginina/análogos & derivados , Endotélio Vascular/metabolismo , Taxa de Filtração Glomerular , Microcirculação , Ácido Úrico/farmacologia , Idoso , Angiografia/métodos , Arginina/metabolismo , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Fatores de Risco , Fatores Sexuais , Ácido Úrico/metabolismo
8.
Intern Med ; 48(5): 273-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19252347

RESUMO

OBJECTIVE: To verify the relationships between the values of plasma glucose (PG) and hemoglobin A(1c)(HbA(1c)) in type 2 diabetic outpatients. METHODS: The pre- and postbreakfast PG and HbA(1c) values were monitored every month for 44-90 months. The single regression lines between the values of PG and HbA(1c) were compared for the slopes and intercepts on the designated ordinates of the regression lines. PATIENTS OR MATERIALS: Nine patients of type 2 diabetes not treated with insulin: three males and six females, aged 43-79 years participated. RESULTS: The HbA(1c) level was combined with the pre- and postbreakfast PG values obtained at one month prior to its determination, because the combinations were correlated most strongly. The slopes of the regression line ranged from 0.33-0.50%/mmol/L and the intercepts at PG level equal to 9.6 mmol/L ranged from 6.95-9.77% in the relationship between the values of 1-month earlier prebreakfast PG and HbA(1c). Twenty-eight pairs had significantly different intercepts. Meanwhile, there was no pair that had significantly different slopes. Similar results were obtained in the relationship between the values of 1-month earlier postbreakfast PG and HbA(1c). CONCLUSION: There was interindividual divergence of the regression lines which was due to the difference in the intercepts but not the slopes.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/metabolismo , Modelos Biológicos , Adulto , Idoso , Diabetes Mellitus Tipo 2/fisiopatologia , Jejum/sangue , Feminino , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial/fisiologia
9.
Am J Med Sci ; 332(3): 142-7, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16969146

RESUMO

We herein describe the rare case of a 41-year-old woman with oncogenic osteomalacia due to a tumor in the maxillary sinus who presented with chronic general pain that had been gradually deteriorating. The patient's laboratory findings revealed hypophosphatemia due to renal phosphate wasting, an inappropriately low serum 1 alpha,25-dihydroxyvitamin D3 level for hypophosphatemia and an unusually high serum level of fibroblast growth factor 23 (FGF23). The causative tumor was surgically removed, resulting in a rapid resolution of the patient's biochemical abnormalities. An improvement of the abnormal multiple deposits on (99)Technetium-methylene diphosphonate bone scintigraphy and an increase in the bone metabolism markers suggested the development of bone remodeling within 49 days after the operation. The pathologic diagnosis of the tumor was a "phosphaturic mesenchymal tumor, mixed with a connective tissue variant." The expression of FGF23 was demonstrated in the tumor by the immunohistochemical techniques and a Western analysis.


Assuntos
Condrossarcoma Mesenquimal/complicações , Neoplasias do Seio Maxilar/complicações , Osteomalacia/etiologia , Adulto , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Fatores de Tempo
10.
Diabetes Metab Res Rev ; 22(1): 64-71, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16028217

RESUMO

BACKGROUND: Cyclic AMP (cAMP) plays a pivotal role in insulin secretion induced by incretins. The effects of the second messenger extend to many sites and there has been much controversy on the mechanisms. The aim of this study was to examine how cAMP amplified insulin exocytosis. METHODS: Rat islets were permeabilized with alpha-toxin to measure insulin exocytosis in the fixed conditions of Ca(2+) and ATP. The effects of several agents on insulin exocytosis were observed in perifusion experiments. RESULTS: Cyclic AMP enhanced the Ca(2+)-induced insulin release by around 30%, independent of Ca(2+) concentrations between 10 and 3000 nmol/L. A cAMP-GEF selective cAMP analogue, 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate, also amplified insulin release. The effect disappeared in the absence of ATP. Conversely, cAMP-independent gradual increase in insulin release was observed with ATP. These results suggested that the site of action of cAMP-GEF existed proximal to that of ATP. An analogue selective to PKA, N(6)-Benzoyladenosine-3',5'-cyclic monophosphate, had little effect. Also, a PKA-selective inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide, reduced insulin releases induced by 1000 nmol/L Ca(2+), but did not influence the relative increase produced by Ca(2+) and cAMP. CONCLUSION: Cyclic AMP potentiated Ca(2+) and ATP-induced exocytosis to a similar relative extent independent of Ca(2+) concentrations. The process appeared to be mainly mediated by cAMP-GEF. In addition, the cAMP/cAMP-GEF pathway may enhance insulin release by replenishing the readily releasable pool.


Assuntos
Trifosfato de Adenosina/farmacologia , Cálcio/farmacologia , AMP Cíclico/farmacologia , Exocitose/efeitos dos fármacos , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Animais , Secreção de Insulina , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Masculino , Ratos , Ratos Wistar , Transdução de Sinais
11.
FEBS Lett ; 579(7): 1602-6, 2005 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-15757648

RESUMO

To explore how the sulfonylurea receptor (SUR1) is involved in docking and fusion of insulin granules, dynamic motion of single insulin secretory granules near the plasma membrane was examined in SUR1 knock-out (Sur1KO) beta-cells by total internal reflection fluorescence microscopy. Sur1KO beta-cells exhibited a marked reduction in the number of fusion events from previously docked granules. However, the number of docked granules declined during stimulation as a consequence of the release of docked granules into the cytoplasm vs. fusion with the plasma membrane. Thus, the impaired docking and fusion results in decreased insulin exocytosis from Sur1KO beta-cells.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Exocitose , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Vesículas Secretórias/metabolismo , Animais , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Insulina/análise , Secreção de Insulina , Ilhotas Pancreáticas/ultraestrutura , Camundongos , Camundongos Knockout , Microscopia de Fluorescência , Canais de Potássio Corretores do Fluxo de Internalização , Receptores de Droga , Vesículas Secretórias/química , Vesículas Secretórias/genética , Receptores de Sulfonilureias
12.
Eur J Endocrinol ; 151(5): 587-94, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15538937

RESUMO

OBJECTIVES: The examination of potential associations between Graves' disease and thyrotropin-producing pituitary adenoma (TSHoma) after treatment using octreotide, and of the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma). DESIGN AND METHODS: A specimen of resected TSHoma tissue from our case was immunohistochemically examined for expression of somatostatin receptor 2A (SSTR2A) and PPAR gamma. Specimens of thyroid tissue from two cases with Hashimoto's thyroiditis were immunohistochemically examined for expression of SSTR2A. RESULTS: Expression of SSTR2A and PPAR gamma was identified in TSHoma cells. SSTR2A was also expressed in lymphocytes that had infiltrated thyroid tissue in Hashimoto's thyroiditis. In previous reports, three of four patients with TSHoma displayed Graves' disease after tumor resection, and TSH is also known to play a major role in regulating immunomodulatory gene expression in thyrocytes. CONCLUSIONS: Both the immunomodulatory effects of octreotide on intrathyroidal lymphocytes and rapid reductions in TSH may contribute to the onset of Graves' disease. Patients with TSHoma-associated autoimmune thyroiditis should undergo careful follow-up for development of Graves' disease after treatment. Both octreotide and the PPAR gamma receptor-activating ligands, thiazolidinediones, may be effective for patients with TSHoma.


Assuntos
Adenoma/tratamento farmacológico , Antineoplásicos Hormonais/efeitos adversos , Doença de Graves/etiologia , Octreotida/efeitos adversos , Neoplasias Hipofisárias/tratamento farmacológico , Tireotropina/biossíntese , Adenoma/metabolismo , Adulto , Antineoplásicos Hormonais/uso terapêutico , Feminino , Humanos , Linfócitos/metabolismo , Linfócitos/patologia , Octreotida/uso terapêutico , PPAR gama/metabolismo , Neoplasias Hipofisárias/metabolismo , Receptores de Somatostatina/metabolismo , Glândula Tireoide/patologia , Tireoidite Autoimune/complicações , Tireoidite Autoimune/metabolismo , Tireoidite Autoimune/patologia , Tireoidite Autoimune/fisiopatologia
13.
J Hum Genet ; 49(11): 629-634, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15490285

RESUMO

Type 2 diabetes mellitus is a heterogeneous disorder, and the development of type 2 diabetes mellitus is associated with both insulin secretion defect and insulin resistance. The primary metabolic defect leading to type 2 diabetes mellitus has been thought to be varied among populations, especially in Japanese and Caucasians. Here, we have done the genome-wide scan for type 2 diabetes mellitus using 102 affected Japanese sib-pairs to identify the genetic factors predisposing to type 2 diabetes mellitus. Nonparametric linkage analysis showed one suggestive evidence for linkage to 11p13-p12 [D11S905: two-point maximum LOD score (MLS) of 2.89 and multipoint MLS of 2.32] and one nominally significant evidence for linkage to 6q15-q16 (D6S462: two-point MLS of 2.02). Interestingly, the 11p13-p12 region was reported to be a susceptibility locus for Japanese type 2 diabetes mellitus with suggestive evidence of linkage, and D11S905 was within 5 cM to D11S935 with the highest MLS in the previous linkage analysis reported. The only overlapped susceptibility region with suggestive evidence of linkage for Japanese type 2 diabetes mellitus was D11S935-D11S905 among the three reports including this study. These results taken together suggest that a susceptibility gene for type 2 diabetes mellitus in Japanese will reside in 11p13-p12.


Assuntos
Cromossomos Humanos Par 11/genética , Diabetes Mellitus Tipo 2/genética , Ligação Genética , Genoma Humano , Predisposição Genética para Doença , Humanos , Japão , Escore Lod
14.
Diabetes Res Clin Pract ; 63(3): 171-7, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14757288

RESUMO

We examined the correlations of hemoglobin A(1c) (HbA(1c)) with each plasma glucose (PG) level obtained at 0 (the same day), 1 and 2 month(s) prior to HbA(1c) determination. Data were from glycemic profiles of four patients of type 2 diabetes mellitus treated with tablets whose HbA(1c) and pre- and post-breakfast PG levels were monitored each month. There was no significant difference in the correlation coefficients in cases 1 and 2, who presented with linear glycemic time courses. In contrast, HbA(1c) correlated with 1-month-earlier pre-breakfast PG level more strongly than 2-month-earlier post-breakfast PG level in cases 3 and 4, and than same-day post-breakfast PG level in case 3 (P<0.05, ANOVA). The cases 3 and 4 presented with fluctuating glycemic time courses. Samples were separated into upslope's and downslope's sections according to HbA(1c) fluctuation in the latter two cases. Reflecting around the 1-month lag between HbA(1c) and PG, the two sections' regression lines for PG versus HbA(1c) corresponded in the only samples related to 1-month-earlier pre- and post-breakfast PG (t-test). In conclusion, it appears that pre- and post-breakfast PG levels are the most reliable predictors of 1-month-later HbA(1c) in type 2 diabetic outpatients who undergo medical examinations every month.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/análise , Adulto , Idoso , Jejum , Feminino , Humanos , Cinética , Masculino , Análise de Regressão , Fatores de Tempo
15.
Am J Med Sci ; 327(1): 49-54, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14722398

RESUMO

We describe the case of a 64-year-old woman with Good syndrome who presented with watery diarrhea and abdominal distention caused by cytomegalovirus (CMV) duodenoenteritis. Thymoma and hypogammaglobulinemia were first identified when the patient was 58 years old. She had repeatedly complained of symptoms even after thymectomy. Abdominal radiography revealed multiple air-fluid levels, and computed tomography revealed ascites and dilation of the small intestine. Immunofluorescent staining of specimens obtained by duodenal mucosal biopsy revealed intracellular inclusion bodies of CMV, although serum CMV pp65 antigenemia assays yielded negative results. CMV infection of the small intestine caused mucosal edema resulting in malabsorption. The patient was treated using ganciclovir and an immunoglobulin preparation with a high titer of antibodies against CMV (CMV-Ig), and subsequently made a rapid recovery from abdominal symptoms. When patients with Good syndrome complain of abdominal symptoms, particularly chronic diarrhea, a diagnosis of CMV gastroenteritis should not be excluded, even if negative results are obtained for CMV pp65 antigenemia assays. Combination therapy of ganciclovir and CMV-Ig seems useful for patients with CMV gastroenteritis.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Duodenite/tratamento farmacológico , Gastroenterite/tratamento farmacológico , Timoma/complicações , Neoplasias do Timo/complicações , Infecções por Citomegalovirus/complicações , Quimioterapia Combinada , Duodenite/complicações , Duodenite/virologia , Feminino , Ganciclovir/uso terapêutico , Gastroenterite/complicações , Gastroenterite/virologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pessoa de Meia-Idade , Timectomia , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Resultado do Tratamento
16.
Am J Physiol Endocrinol Metab ; 286(3): E463-71, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14613926

RESUMO

This study examines the effect of epinephrine, a known physiological inhibitor of insulin secretion, on the membrane potential of pancreatic islet cells from sulfonylurea receptor-1 (ABCC8)-null mice (Sur1KO), which lack functional ATP-sensitive K+ (KATP) channels. These channels have been argued to be activated by catecholamines, but epinephrine effectively inhibits insulin secretion in both Sur1KO and wild-type islets and in mice. Isolated Sur1KO beta-cells are depolarized in both low (2.8 mmol/l) and high (16.7 mmol/l) glucose and exhibit Ca(2+)-dependent action potentials. Epinephrine hyperpolarizes Sur1KO beta-cells, inhibiting their spontaneous action potentials. This effect, observed in standard whole cell patches, is abolished by pertussis toxin and blocked by BaCl2. The epinephrine effect is mimicked by clonidine, a selective alpha2-adrenoceptor agonist and inhibited by alpha-yohimbine, an alpha2-antagonist. A selection of K+ channel inhibitors, tetraethylammonium, apamin, dendrotoxin, iberiotoxin, E-4130, chromanol 293B, and tertiapin did not block the epinephrine-induced hyperpolarization. Analysis of whole cell currents revealed an inward conductance of 0.11 +/- 0.04 nS/pF (n = 7) and a TEA-sensitive outward conductance of 0.55 +/- 0.08 nS/pF (n = 7) at -60 and 0 mV, respectively. Guanosine 5'-O-(3-thiotriphosphate) (100 microM) in the patch pipette did not significantly alter these currents or activate novel inward-rectifying K+ currents. We conclude that epinephrine can hyperpolarize beta-cells in the absence of KATP channels via activation of low-conductance BaCl2-sensitive K+ channels that are regulated by pertussis toxin-sensitive G proteins.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Epinefrina/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/fisiologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/deficiência , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Células Cultivadas , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/fisiologia , Masculino , Camundongos , Camundongos Knockout , Nifedipino/farmacologia , Canais de Potássio/classificação , Canais de Potássio/deficiência , Canais de Potássio Corretores do Fluxo de Internalização , Receptores de Droga , Receptores de Sulfonilureias
17.
Hypertens Res ; 26(10): 807-13, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14621184

RESUMO

Pulse wave velocity (PWV) is useful for the evaluation of aortic stiffness. The brachial-ankle PWV (baPWV) and carotid PWV (from heart to carotid) were compared to study the relation of these two types of PWVs to diabetic complications in patients with type 2 diabetes mellitus. The baPWV was determined by oscillometrically measuring the pulse volume record at the upper arm and ankles. The carotid PWV was measured tonometrically. Ninety patients with type 2 diabetes mellitus were divided into tertile groups on the basis of baPWV or carotid PWV. The correlations of these variables with albuminuria, peripheral neuropathy, coefficient of variation of R-R intervals (CV R-R) on the electrocardiogram at rest, and retinopathy were examined by logistic regression analysis. After adjustment for age, systolic blood pressure, and duration of diabetes, logistic regression analysis showed that baPWV was directly related to the frequencies of albuminuria, decreased CV R-R, peripheral neuropathy, and retinopathy. In contrast, carotid PWV did not significantly correlate with any diabetic complications. We conclude that oscillometrically determined baPWV is related to the risk of diabetic microvascular disease in patients with type 2 diabetes mellitus and suggested to be useful for assessing risk factors of diabetic complications.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/fisiopatologia , Hipertensão Renal/diagnóstico , Hipertensão Renal/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/fisiopatologia , Tornozelo/irrigação sanguínea , Aorta/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Artéria Braquial/fisiologia , Nefropatias Diabéticas/fisiopatologia , Retinopatia Diabética/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Pulsátil/fisiologia
18.
Stroke ; 34(1): 164-70, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12511769

RESUMO

BACKGROUND AND PURPOSE: ATP-sensitive K+ (K(ATP)) channels have been implicated in the mechanism of neuronal ischemic preconditioning. To evaluate the role of neuronal/beta-cell-type K(ATP) channels, SUR1 null (Sur1KO) mice lacking (K(IR)6.x/SUR1)(4) K(ATP) channels were subjected to a preconditioning protocol with the use of double carotid occlusion. METHODS: Wild-type C57BL/6 and Sur1KO mice were subjected to a double carotid block for 40 minutes with or without a 20-minute preconditioning block. After a 10-day reperfusion period, damage was assessed histologically in the hippocampal CA1, CA2, and CA3 areas and in the dentate gyrus. The neuroprotective effects of intracerebroventricular injections of diazoxide, which selectively affects mitochondria versus opening SUR1-type K(ATP) channels, and 5-hydroxydecanoate, a selective blocker of mitoK(ATP) channels, were evaluated with the same protocol. RESULTS: Neurons in the CA1 region of both Sur1KO and wild-type animals subjected to a 20-minute ischemic insult were protected equally from neuronal damage produced by a subsequent 40-minute ischemic period. Pretreatment with diazoxide protected both Sur1KO and wild-type neurons, while 5-hydroxydecanoate augmented neurodegeneration in both strains of animals when administered before a 20-minute bout of ischemia. CONCLUSIONS: SUR1-based K(ATP) channels are not obligatory for neuronal preconditioning or augmentation of neurodegeneration by 5-hydroxydecanoate.


Assuntos
Isquemia Encefálica/etiologia , Hipocampo/irrigação sanguínea , Precondicionamento Isquêmico , Camundongos Knockout , Canais de Potássio/genética , Canais de Potássio/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Isquemia Encefálica/patologia , Sobrevivência Celular/efeitos dos fármacos , Ácidos Decanoicos/farmacologia , Diazóxido/uso terapêutico , Hipocampo/patologia , Hidroxiácidos/farmacologia , Hipóxia/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/uso terapêutico , Bloqueadores dos Canais de Potássio/uso terapêutico
19.
Diabetes ; 51(12): 3440-9, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12453898

RESUMO

Whereas the loss of ATP-sensitive K(+) channel (K(ATP) channel) activity in human pancreatic beta-cells causes severe hypoglycemia in certain forms of hyperinsulinemic hypoglycemia, similar channel loss in sulfonylurea receptor-1 (SUR1) and Kir6.2 null mice yields a milder phenotype that is characterized by normoglycemia, unless the animals are stressed. While investigating potential compensatory mechanisms, we found that incretins, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), can increase the cAMP content of Sur1KO islets but do not potentiate glucose-stimulated insulin release. This impairment is secondary to a restriction in the ability of Sur1KO beta-cells to sense cAMP correctly. Potentiation does not appear to require cAMP-activated protein kinase (PKA) because H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) and KT5720, inhibitors of PKA, do not affect stimulation by GLP-1, GIP, or exendin-4 in wild-type islets, although they block phosphorylation of cAMP-response element-binding protein. The impaired incretin response in Sur1KO islets is specific; the stimulation of insulin release by other modulators, including mastoparan and activators of protein kinase C, is conserved. The results suggest that the defect responsible for the loss of cAMP-induced potentiation of insulin secretion is PKA independent. We hypothesize that a reduced release of insulin in response to incretins may contribute to the unexpected normoglycemic phenotype of Sur1KO mice versus the pronounced hypoglycemia seen in neonates with loss of K(ATP) channel activity.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Carbazóis , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , AMP Cíclico/fisiologia , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização , Canais de Potássio/fisiologia , Receptores de Droga/fisiologia , Sulfonamidas , Animais , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ativação Enzimática/fisiologia , Inibidores Enzimáticos/farmacologia , Glucagon , Peptídeo 1 Semelhante ao Glucagon , Peptídeos Semelhantes ao Glucagon , Glucose/farmacologia , Indóis/farmacologia , Secreção de Insulina , Isoquinolinas/farmacologia , Camundongos , Camundongos Knockout/genética , Fragmentos de Peptídeos/fisiologia , Canais de Potássio/deficiência , Canais de Potássio/genética , Proteína Quinase C/metabolismo , Pirróis/farmacologia , Receptores de Droga/deficiência , Receptores de Droga/genética , Valores de Referência , Receptores de Sulfonilureias
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