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BACKGROUND: Type 2 diabetes is caused by interactions between genetic and environmental factors. Our previous studies reported that paired box 6 mutation heterozygosity (Pax6(m/+)) led to defective proinsulin processing and subsequent abnormal glucose metabolism in mice at 6 months of age. However, high-fat diet exposure could be an important incentive for diabetes development. In this study, we aimed to develop a novel diabetic model imitating human type 2 diabetes by exposing Pax6(m/+) mice to high-fat diet and to explore the underlying mechanism of diabetes in this model. METHODS: Over 300 Pax6(m/+) and wild-type male weanling mice were randomly divided into two groups and were fed an high-fat diet or chow diet for 6-10 weeks. Blood glucose and glucose tolerance levels were monitored during this period. Body weights, visceral adipose weights, blood lipid profiles and insulin sensitivity (determined with an insulin tolerance test) were used to evaluate obesity and insulin resistance. Proinsulin processing and insulin secretion levels were used to evaluate pancreatic ß cell function. RESULTS: After 6 weeks of high-fat diet exposure, only the Pax6(m/+) mice showed dramatic postloading hyperglycaemia. These mice exhibited significant high-fat diet-induced visceral obesity and insulin resistance and displayed defective prohormone convertase 1/3 production, an increased proinsulin:total insulin ratio and impaired early-phase insulin secretion, because of the Pax6 mutation. Hyperglycaemia worsened progressively over time with the high-fat diet, and most Pax6(m/+) mice on high-fat diet developed diabetes or impaired glucose tolerance after 10 weeks. Furthermore, high-fat diet withdrawal partly improved blood glucose levels in the diabetic mice. CONCLUSIONS: By combining the Pax6(m/+) genetic background with an high-fat diet environment, we developed a novel diabetic model to mimic human type 2 diabetes. This model is characterized by impaired insulin secretion, caused by the Pax6 mutation, and high-fat diet-induced insulin resistance and therefore provides an ideal tool for research on type 2 diabetes pathogenesis and therapies.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Proteínas do Olho/metabolismo , Proteínas de Homeodomínio/metabolismo , Resistência à Insulina , Ilhotas Pancreáticas/metabolismo , Mutação , Obesidade Abdominal/etiologia , Fatores de Transcrição Box Pareados/metabolismo , Proteínas Repressoras/metabolismo , Animais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/etiologia , Proteínas do Olho/genética , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Heterozigoto , Proteínas de Homeodomínio/genética , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Masculino , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Obesidade Abdominal/complicações , Obesidade Abdominal/fisiopatologia , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/genética , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações , Estado Pré-Diabético/etiologia , Estado Pré-Diabético/metabolismo , Proinsulina/sangue , Proinsulina/metabolismo , Pró-Proteína Convertase 1/metabolismo , Distribuição Aleatória , Proteínas Repressoras/genética , Desmame , Aumento de PesoRESUMO
OBJECTIVE: To investigate the changes of serum programmed cell death 5 (PDCD5) levels in patients with critical illnesses including systemic inflammatory response syndrome (SIRS, except sepsis), sepsis (except severe sepsis) and severe sepsis. METHODS: A total of 78 patients were enrolled in this study, of whom, 28 were with SIRS, 23 with sepsis and 27 with severe sepsis. Twenty-two healthy individuals were included as controls. The levels of serum PDCD5 were evaluated by enzyme-linked immune sorbent assay. And the correlation analyses were made in the levels of sreum PDCD5 and acute physiology and chronic health evaluation II(APACHE II), high-sensitivity C-reactive protein(hs-CRP), white blood cell count, neutrophil count and age factors. RESULTS: Serum PDCD5 levels in the SIRS, sepsis and severe sepsis groups were (19.07 ± 8.91), (29.03 ± 13.27) and (42.83 ± 17.32) µg/L respectively, which were significantly higher than that in the healthy control group (0.32 ± 0.02) µg/L. Serum PDCD5 levels in SIRS, sepsis and severe sepsis groups were gradually increased with significant difference at any in-between comparison (P<0.05). Moreover, serum PDCD5 levels were positively correlated with the acute physiology and chronic health evaluation II (APACHE II) score (r=0.572, P<0.05). CONCLUSION: The serum PDCD5 levels in the critically ill patients with sepsis were progressively increased with the worsened condition. The up-regulated expression of PDCD5 may play an important role in the development and progression of sepsis.
Assuntos
Proteínas Reguladoras de Apoptose/sangue , Proteínas de Neoplasias/sangue , Sepse/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para CimaRESUMO
Insufficient pupil dilation, a common challenge in cataract surgery, may lead to surgical complications. After a quality improvement project was conducted, the proportion of patients with the desired pupil dilation of > or = 7 mm increased from 39.5% to 88.0% (Implementation phase) and then to 82.2% (Sustaining phase).
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Extração de Catarata , Procedimentos Clínicos , Midriáticos/administração & dosagem , Pupila/efeitos dos fármacos , Distribuição de Qui-Quadrado , Humanos , Melhoria de Qualidade , Singapura , Resultado do TratamentoRESUMO
OBJECTIVE: Coronary flow velocity reserve (CFVR) is an important indicator of coronary endothelial functions and microcirculation. Pulse wave velocity (PWV) reflects the degree of aortic sclerosis and it is an independent predictor of cardiovascular events. The present study was designed to evaluate the correlation of large artery stiffness and CFVR. METHODS: A total of 101 consecutive subjects were enrolled to measure the brachial-ankle pulse wave velocity (baPWV). According to the presence or absence of higher baPWV (> 1400 cm/s), they were divided into 2 groups. Transthoracic echocardiography was employed to measure coronary flow velocity in coronary left anterior descending (LAD). Then after an intravenous infusion of adenosine triphosphate, the velocity of blood flow was measured when the vessel was in maximal dilation. The ratio of flow velocity of those in maximal dilation to those at rest was CFVR. RESULTS: The subjects with a higher baPWV (> 1400 cm/s) were markedly elder and had higher risks of hypertension and diabetes. Thus age, hypertension and diabetes contributed to arteriosclerosis. More importantly, the subjects with a higher baPWV (> 1400 cm/s) had a much lower level of CFVR (2.66 ± 0.74 vs 2.95 ± 0.76; P < 0.01) than those with a lower baPWV (< 1400 cm/s). Furthermore correlation analysis showed that CFVR and baPWV levels were significantly negatively correlated (r = -0.35, P < 0.01). CONCLUSIONS: A negative correlation exists between artery stiffness and coronary flow velocity reserve. The increased vascular stiffness may impair coronary endothelial function, cause the dysfunction of coronary microcirculation and raise the risks of cardiovascular events.
Assuntos
Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Rigidez Vascular , Idoso , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de PulsoRESUMO
AIM: Ghrelin is involved in regulating the differentiation of mesoderm-derived precursor cells. The aim of this study was to investigate whether ghrelin modulated the differentiation of human embryonic stem (hES) cells into cardiomyocytes and, if so, whether the effect was mediated by growth hormone secretagogue receptor 1α (GHS-R1α). METHODS: Cardiomyocyte differentiation from hES cells was performed according to an embryoid body (EB)-based protocol. The cumulative percentage of beating EBs was calculated. The expression of cardiac-specific markers including cardiac troponin I (cTnI) and α-myosin heavy chain (α-MHC) was detected using RT-PCR, real-time PCR and Western blot. The dispersed beating EBs were examined using immunofluorescent staining. RESULTS: The percentage of beating EBs and the expression of cTnI were significantly increased after ghrelin (0.1 and 1 nmol/L) added into the differentiation medium. From 6 to 18 d of differentiation, the increased expression of cTnI and α-MHC by ghrelin (1 nmol/L) was time-dependent, and in line with the alteration of the percentages of beating EBs. Furthermore, the dispersed beating EBs were double-positively immunostained with antibodies against cTnI and α-actinin. However, blockage of GHS-R1α with its specific antagonist D-[lys(3)]-GHRP-6 (1 µmol/L) did not alter the effects of ghrelin on cardiomyocyte differentiation. CONCLUSION: Our data show that ghrelin enhances the generation of cardiomyocytes from hES cells, which is not mediated via GHS-R1α.
Assuntos
Células-Tronco Embrionárias/citologia , Grelina/metabolismo , Miócitos Cardíacos/citologia , Receptores de Grelina/metabolismo , Diferenciação Celular , Linhagem Celular , Células-Tronco Embrionárias/metabolismo , Humanos , Miócitos Cardíacos/metabolismoRESUMO
BACKGROUND: The purpose of present study was to explore the mechanism of nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B(PKB/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways after intervention of advanced glycosylation end products (AGEs) on rat bone-marrow stromal cells (BMSCs). METHODS: Prepare and identify AGEs. BMSCs were isolated from 16 SD rats and cultured with different concentration of AGEs. Cell viability was detected by cell counting kit-8 (CCK-8). BMSCs were cultured with AGEs (0.25 mg/ml) for 30 min, 12 h, 24 h, 72 h and 120 h. In addition, BMSCs were cultured with AGEs, AGEs + JNK inhibitor and AGEs + P38 inhibitor for 24 h and 48 h, respectively. Western blotting and RT-PCR were used to determine the protein and mRNA expression levels, respectively. RESULTS: Cell viability of BMSCs was significantly correlated with concentration and effect time of AGEs (P < 0.05), and the most appropriate concentration was 0.25 mg/ml. AGEs stimulation significantly increased the protein expression levels of NF-κB p65, JNK, p38 (P < 0.05), decreased IκB (P < 0.05), but had no effect on the protein expression of Akt in BMSCs (P > 0.05). At the mRNA level, JNK and p38 inhibitors significantly reduced the levels of NF-κB p65, p38 and JNK, increased IκB (P > 0.05), but had no effect on Akt in BMSCs (P > 0.05). At the protein level, JNK and p38 inhibitors notably decreased the expression of NF-κB p65, p38, p-JNK, P-IκB and JNK (P < 0.001), and increased IκB (P < 0.05). CONCLUSION: Advanced glycosylation end products can inhibit the proliferation of bone-marrow stromal cells through activating MAPK pathway.
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Células da Medula Óssea/metabolismo , Proliferação de Células , Produtos Finais de Glicação Avançada/metabolismo , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/metabolismo , Animais , Células da Medula Óssea/fisiologia , Células Cultivadas , MAP Quinase Quinase 4/metabolismo , Masculino , Células-Tronco Mesenquimais/fisiologia , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Graves' disease (GD) occurs due to an autoimmune dysfunction of thyroid gland cells, leading to manifestations consistent with hyperthyroidism. Various studies have confirmed the link between autoimmune conditions and changes in the composition of intestinal microbial organisms. However, few studies have assessed the relationship between the GD and the changes in intestinal microbiota. Therefore, the present study aimed to investigate changes in intestinal flora that may occur in the setting of GD. Thirty-nine patients with GD and 17 healthy controls were enrolled for fecal sample collection. 16S rRNA sequencing was used to analyze the diversity and composition of the intestinal microbiota. High-throughput sequencing of 16S rRNA genes of intestinal flora was performed on Illumina Hiseq2500 platform. Comparing to healthy individuals, the number of Bacilli, Lactobacillales, Prevotella, Megamonas and Veillonella strains were increased, whereas the number of Ruminococcus, Rikenellaceae and Alistipes strains were decreased among patients with GD. Furthermore, patients with GD showed a decrease in intestinal microbial diversity. Therefore, it indicates that the diversity of microbial strains is significantly reduced in GD patients, and patients with GD will undergo significant changes in intestinal microbiota, by comparing the intestinal flora of GD and healthy controls. These conclusions are expected to provide a preliminary reference for further researches on the interaction mechanism between intestinal flora and GD.
Assuntos
Microbioma Gastrointestinal/fisiologia , Doença de Graves/microbiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Microbioma Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
The researches of therapeutic cloning and somatic cell reprogramming, two strategies used to generate patient-specific autologous stem cells, have recently made great progress. Therapeutic cloning refers to derivation of embryonic stem cells from blastocyst produced by somatic cell nuclear transfer, whereas somatic cell reprogramming refers to establishment of induced pluripotent stem (iPS) cells from differentiated somatic cells by ectopic expression of specific transcription factors. The two strategies differ in their methodological approaches, technical obstacles and ethical debates, but confront similar problems including the differentiation of stem cells and the feasibility of cell-replacement therapy. This review discusses the research advance of these two biotechnologies and summarizes their difference and similarity.
Assuntos
Reprogramação Celular , Células-Tronco Pluripotentes Induzidas , Células-Tronco/citologia , Animais , Células Clonais , Humanos , Técnicas de Transferência Nuclear , Fatores de TranscriçãoRESUMO
AIM: To investigate the effects of rosiglitazone (RGZ) on expression of interleukin-18 (IL-18) and caspase-1 in liver of non-alcoholic fatty liver disease (NAFLD) rats. METHODS: Twenty-eight Sprague-Dawley (SD) rats were randomly divided into control, NAFLD, and RGZ treated NAFLD groups. A NAFLD rat model of NAFLD was established by feeding the animals with a high-fat diet for 12 wk. The NAFLD animals were treated with RGZ or vehicle for the last 4 wk (week 9-12) and then sacrificed to obtain liver tissues. Histological changes were analyzed with HE, oil red O and Masson's trichrome staining. Expressions of IL-18 and caspase-1 were detected using immunohistochemical staining and semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis. RESULTS: The expression levels of both IL-18 and caspase-1 were higher in the liver of NAFLD group than in the control group. Steatosis, inflammation and fibrosis, found in the liver of NAFLD rats, were significantly improved 4 wk after RGZ treatment. The elevated hepatic IL-18 and caspase-1 expressions in NAFLD group were also significantly attenuated after RGZ treatment. CONCLUSION: RGZ treatment can ameliorate increased hepatic IL-18 production and histological changes in liver of NAFLD rats. The beneficial effects of RGZ on NAFLD may be partly due to its inhibitory effect on hepatic IL-18 production.
Assuntos
Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Hipoglicemiantes/farmacologia , Interleucina-18/metabolismo , Fígado/metabolismo , Tiazolidinedionas/farmacologia , Animais , Caspase 1/metabolismo , Modelos Animais de Doenças , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , RosiglitazonaRESUMO
A 16-year-old "female" patient presented as hypertension, hypokalemia, male pseudohermaphroditism, lowered gonadal steroids and cortisol, elevated adrenocorticotropic hormone and pituitary gonadotropin, and 46 XY karyotype. The patient was diagnosed as 17 alpha-hydroxylase deficiency, a rare case of congenital adrenal hyperplasia. "She" chose to remain female appearance and social gender after negotiation with the parents. Cryptor-chidism of both inguinal canals was surgically removed for preventing canceration. After the surgery, a very small daily dose of dexamethasone (0.187 5 mg at bedtime) was enough to control hypertension and hypokalemia, and the therapy of conjugated estrogens (Premarin) was given to promote the development of female characters. After 6 months of treatment, normotension and normokalemia remained, and pubarche and mammogenesis emerged.
Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Dexametasona/uso terapêutico , Esteroide 17-alfa-Hidroxilase/sangue , Adolescente , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/metabolismo , Humanos , MasculinoRESUMO
OBJECTIVE: To investigate the IL-18 expression in the thyroid tissues of Hashimoto's thyroiditis (HT) and its cellular localization and the effect of interferon-gamma (IFN-gamma) on the interleukin- (IL)-18 expression in thyrocytes. METHODS: RT-PCR and immunohistochemistry were used to detect the IL-18 expression and its cellular localization in the thyroid tissues biopsy specimens of 6 HT patients with normal thyroid function, 6 normal thyroid specimens resected from patients with pharyngeal carcinoma, and 16 specimens of thyroid tissues adjacent to the thyroid adenoma obtained during operation. Thyrocytes were isolated, cultured, and exposed to IL-1beta, tumor necrosis factor-alpha (TNF-alpha), or IFN-gamma for 48 h. RT-PCR and Western blotting were used to detect the IL-18 expression. RESULTS: IL-18 mRNA expression was at an extremely low levels in the normal thyroid tissues and at a significantly higher level in the thyroid tissues of HT. Immunohistochemical staining showed that IL-18 expression was augmented in the thyroid tissues of HT and was mainly localized in the thyroid follicular cells. The IL-18 mRNA expression in the isolated human thyrocytes was dose-dependently elevated by IFN-gamma rather than TNF-alpha or IL-1beta. Western blotting showed that pro-IL-18, but not mature IL-18, was detected in the lysates of the cultured human thyrocytes and the expression of pro-IL-18 was increased by IFN-gamma. CONCLUSION: IL-18 expression is elevated in the thyroid follicular cells of HT. IL-18 is constitutively expressed in the isolated human thyrocytes and its expression is up-regulated by IFN-gamma. Therefore, interplay between IL-18 and IFN-gamma may have an important role in the thyrocytes destruction in HT.
Assuntos
Doença de Hashimoto/metabolismo , Interleucina-18/biossíntese , Glândula Tireoide/metabolismo , Adulto , Proliferação de Células , Células Epiteliais/citologia , Feminino , Doença de Hashimoto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Tireoide/citologiaRESUMO
OBJECTIVE: To study the efficacy and safety of extended-release metformin and Glucophage in treatment of type 2 diabetes mellitus. METHODS: 150 out-patients with type 2 diabetes mellitus visiting 3 hospitals in Beijing were randomly divided into two equal groups: study group treated with extended-release metformin 1500 mg qd for 12 weeks, and control group treated with Glucophage (tablet of metformin, 500 mg, tid) and in for 12 weeks. The levels of fasting plasma glucose (FPG), plasma glucose 2 h after meal (2 hPG), and glycated hemoglobin (HbA1c) were examined before and 12 weeks after treatment. Plasma insulin was detected by radioimmunoassay. RESULTS: Completed study had been obtained in 140 patients, 71 in the control group and 69 in the study group. 12 weeks after treatment there was no significant difference in the FPG level between these two groups (P = 0.07), the postprandial plasma glucose level decreased by 0.4 (-1.4 approximately 1.7) mmol/L in the control group and increased slightly in the study group (P = 0.002), however, the levels plasma glucose area under curve 2 hours after meal in these 2 groups did not changed significantly (P = 0.64). HbA1c decreased in both groups and there was not significant difference between these two groups (P = 0.73). The adverse event rates of the study and control groups were 10.8% and 4.3% respectively (P = 0.21), and the main adverse events were gastrointestinal side effects. No serious adverse events were found in both groups, and no patient was withdrawn due to adverse events of medication. CONCLUSION: The efficacy and safety of extended-release metformin within 12 week treatment for type 2 diabetes mellitus is comparable to those of Glucophage treatment with good compliance and mild adverse side effects.
Assuntos
Preparações de Ação Retardada , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Feminino , Gastroenteropatias/induzido quimicamente , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Radioimunoensaio , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate whether ghrelin, a novel endogenous ligand of growth hormone secretagogue receptor (GHS-R), was expressed in the thyroid tissues of different thyroid diseases, and its implication. METHODS: The paraffin-embedded specimens of thyroid tissues from 2000 to 2004 were obtained from 57 patients with different thyroid diseases, including 5 subacute thyroiditis, 8 Hashimoto's thyroiditis, 7 hyperthyroidism (Graves disease), 8 nodular goiter, 5 thyroid adenoma, 3 thyroid lymphoma, 8 papillary carcinoma, 3 follicular carcinoma, 5 medullary carcinoma and 5 undifferentiated carcinoma cases. The specimens of normal peri-adenoma thyroid tissues served as controls. Immunohistochemical staining was used to detect ghrelin expression. RESULTS: (1) ghrelin expression was undetectable in the thyroid tissues of normal control, subacute thyroiditis, Hashimoto's thyroiditis and Graves disease. (2) ghrelin expression was also undetected in the tissues of nodular goiter, thyroid adenoma and thyroid lymphoma. (3) ghrelin-positive staining was found in the tumor cells of different types of thyroid carcinoma. Five cases were positive within 8 cases in papillary carcinoma, 2 cases were positive within 3 cases in follicular carcinoma, 3 cases were positive within 5 cases in medullary carcinoma, 3 cases were positive within 5 cases in undifferentiated carcinoma. CONCLUSION: Ghrelin is expressed in malignant epithelial thyroid neoplasms, but not in autoimmune or inflammatory thyroid diseases and benign nodular thyroid diseases. The results indicate that ghrelin expression may play an important role in the occurrence and development of thyroid carcinoma.
Assuntos
Grelina/metabolismo , Doenças da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Adulto , Idoso , Feminino , Doença de Graves/metabolismo , Doença de Graves/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Glândula Tireoide/classificação , Doenças da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto JovemRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus. METHODS: This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of <40 years were included, and the control group consisted of subjects aged <40 years with normal blood glucose level. RESULTS: In patients with young-onset T2DM, the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%, respectively. Most of the patients were obese, followed irregular diet pattern and sedentary lifestyle, had life or work pressure, and had a family history of diabetes mellitus. Compared with subjects with normal blood glucose level, logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99, 95% confidence interval [CI] 42.37-4714.87), family history of diabetes mellitus (OR 23.46, CI 14.47-38.03), dyslipidemia (OR 2.65, CI 1.54-4.56), diastolic blood pressure (OR 1.02, CI 1.00-1.04), and body mass index (OR 0.95, CI 0.92-0.99) are independent factors for early-onset T2DM. CONCLUSIONS: We observed that abdominal obesity, family history of diabetes mellitus, and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM. It is, therefore, necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.
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Diabetes Mellitus Tipo 2/etiologia , Adulto , Glicemia/análise , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Fatores de Risco , Relação Cintura-QuadrilRESUMO
AIM: To isolate nestin-positive progenitor cells from human fetal pancreas and to detect their surface markers and their capability of proliferation and differentiation into pancreatic islet endocrine cells in vitro. METHODS: Islet-like cell clusters (ICCs) were isolated from human fetal pancreas by using collagenase digestion. The free-floating ICCs were handpicked and cultured in a new dish. After the ICCs developed into monolayer epithelium-like cells, they were passaged and induced for differentiation. Reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence stain, fluorescence-activated cell sorting (FACS) and radioimmunoassay (RIA) were used to detect the expression of cell markers. RESULTS: (1) The monolayer epithelium-like cells had highly proliferative potential and could be passaged more than 16 times in vitro; (2) RT-PCR analysis and immunofluorescence stain showed that these cells expressed both nestin and ABCG2, two of stem cell markers; (3) FACS analysis revealed that CD44, CD90 and CD147 were positive, whereas CD34, CD38, CD45, CD71, CD117, CD133 and HLA-DR were negative on the nestin-positive cells; (4) RT-PCR analysis showed that the mRNA expression of insulin, glucagon and pancreatic-duodenal homeobox gene-1 was detected, whereas the expression of nestin and neurogenin 3 disappeared in these cells treated with serum-free media supplemented with the cocktail of growth factors. Furthermore, the intra-cellular insulin content was detected by RIA after the induction culture. CONCLUSION: Nestin-positive cells isolated from human fetal pancreas possess the characteristics of pancreatic progenitor cells since they have highly proliferative potential and the capability of differentiation into insulin-producing cells in vitro. Interestingly, the nestin-positive pancreatic progenitor cells share many phenotypic markers with mesenchymal stem cells derived from bone marrow.
Assuntos
Proteínas de Filamentos Intermediários/metabolismo , Ilhotas Pancreáticas/citologia , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Biomarcadores , Diferenciação Celular , Divisão Celular , Feto/citologia , Citometria de Fluxo , Humanos , Ilhotas Pancreáticas/embriologia , Mesoderma/citologia , Nestina , FenótipoRESUMO
OBJECTIVE: To verify the hypothesis that selected nestin positive cells derived from human fetal pancreas (according as medical ethnics) have surface markers similar to bone marrow mesenchymal stem cells (MSCs), and that these cells have multilineage potential. METHOD: The cell surface markers were determined by flow cytometry, and then the potential that these cells might be differentiated into adipocytes and osteoplasts were explored. RESULT: These cells have similar surface markers as MSCs of bone marrow origin. These cells was induced to differentiate into adipocytes and osteoplasts. CONCLUSION: Selected nestin positive cells derived from human fetal pancreas have certain characteristics of MSCs.
Assuntos
Adipócitos/citologia , Células da Medula Óssea/citologia , Diferenciação Celular , Células-Tronco Fetais/citologia , Células-Tronco Fetais/metabolismo , Separação Celular/métodos , Células Cultivadas , Células-Tronco Fetais/química , Citometria de Fluxo , Humanos , Proteínas de Filamentos Intermediários , Células-Tronco Mesenquimais/metabolismo , Proteínas do Tecido Nervoso , Nestina , Pâncreas/citologia , Pâncreas/embriologiaRESUMO
BACKGROUND: At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone. METHODS: This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment. RESULTS: At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 µU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 µU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups. CONCLUSIONS: Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated. REGISTRATION NUMBER: ChiCTR-TRC-13003776.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Metformina/efeitos adversos , Metformina/uso terapêutico , Tiazóis/efeitos adversos , Tiazóis/uso terapêutico , Adulto , Glicemia/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/sangue , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Tiazóis/administração & dosagemRESUMO
Kallmann syndrome, a form of idiopathic hypogonadotropic hypogonadism, is characterized by developmental abnormalities of the reproductive system and abnormal olfaction. Despite association of certain genes with idiopathic hypogonadotropic hypogonadism, the genetic inheritance and expression are complex and incompletely known. In the present study, seven Kallmann syndrome pedigrees in an ethnic Han Chinese population were screened for genetic mutations. The exons and intron-exon boundaries of 19 idiopathic hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism)-related genes in seven Chinese Kallmann syndrome pedigrees were sequenced. Detected mutations were also tested in 70 sporadic Kallmann syndrome cases and 200 Chinese healthy controls. In pedigrees 1, 2, and 7, the secondary sex characteristics were poorly developed and the patients' sense of smell was severely or completely lost. We detected a genetic mutation in five of the seven pedigrees: homozygous KAL1 p.R191ter (pedigree 1); homozygous KAL1 p.C13ter (pedigree 2; a novel mutation); heterozygous FGFR1 p.R250W (pedigree 3); and homozygous PROKR2 p.Y113H (pedigrees 4 and 5). No genetic change of the assayed genes was detected in pedigrees 6 and 7. Among the 70 sporadic cases, we detected one homozygous and one heterozygous PROKR2 p.Y113H mutation. This mutation was also detected heterozygously in 2/200 normal controls and its pathogenicity is likely questionable. The genetics and genotype-phenotype relationships in Kallmann syndrome are complicated. Classical monogenic inheritance does not explain the full range of genetic inheritance of Kallmann syndrome patients. Because of stochastic nature of genetic mutations, exome analyses of Kallmann syndrome patients may provide novel insights.
Assuntos
Análise Mutacional de DNA , Síndrome de Kallmann/etnologia , Síndrome de Kallmann/genética , Adolescente , Adulto , Sequência de Aminoácidos , Criança , China , Códon sem Sentido , Éxons , Proteínas da Matriz Extracelular/genética , Saúde da Família , Feminino , Estudos de Associação Genética , Heterozigoto , Homozigoto , Humanos , Hipogonadismo/etnologia , Hipogonadismo/genética , Íntrons , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/genética , Linhagem , Fenótipo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Peptídeos/genética , Homologia de Sequência de Aminoácidos , Adulto JovemRESUMO
OBJECTIVE: To investigate whether TF-1 cell apoptosis-related gene 19 (TFAR19), a novel apoptosis-related protein, is expressed in the tissue of thyroid adenoma (TA) or papillary thyroid carcinoma (PTC) and the cellular location of the expression. METHODS: Thyroid tumor tissue specimens were obtained from six patients with TA and six patients with PTC by surgical biopsies for pathological diagnosis. Normal peri-tumor thyroid tissue from the six TA patients served as control. Immunohistochemical staining was used to detect TFAR19 expression. RESULTS: TFAR19 expression was barely detectable in normal thyroid tissue. However, TFAR19 expression was strongly positive in the thyroid tumor tissue of TA group but negative in that of PTC group. CONCLUSION: Our preliminary data have demonstrated for the first time that TFAR19-related apoptotic pathway is activated in the tumor cells of TA and inhibited in those of PTC. The imbalance between cell apoptosis and proliferation might have an important role in the pathogenesis of PTC.