RESUMO
OBJECTIVES: Metabolic surgery has been proven to be widely effective for the control of glucose and weight in patients with type 2 diabetes and obesity. However, the effects of bariatric surgery on nonobesity type 2 diabetes and its metabolism are still unclear. This study aimed to measure the effects of duodenal-jejunal exclusion on glycometabolism in nonobese rats with type 2 diabetes and to investigate its mechanisms. METHODS: Goto-Kakizaki rats and Sprague-Dawley rats were divided into duodenal-jejunal exclusion operation groups and sham operation groups, respectively. The glucose-relative parameters were measured before and after operation. Eight weeks postoperation, the levels of the key regulators of intestinal gluconeogenesis and the crucial proteins of hepatic insulin signalling were evaluated. RESULTS: Postoperatively, the concentrations of blood glucose declined, and the insulin sensitivity increased significantly in rats with diabetes. However, there was no obvious reduction in weight. Eight weeks postoperatively, the mRNA levels of glucose-6-phosphatase and phosphoenolpyruvate pyruvate kinase in the jejunum and the levels of insulin receptor substrate-2 and glucose transporter-2 in the liver were significantly increased compared with the rats that had undergone the sham operation. CONCLUSIONS: Duodenal-jejunal exclusion surgery is an effective procedure for improving glucose metabolism independent of weight loss in nonobese rats with diabetes. The molecular mechanisms might be associated with a series of processes, including intestinal gluconeogenesis and the hepatic insulin signaling pathway.
Assuntos
Cirurgia Bariátrica , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/cirurgia , Duodeno/cirurgia , Gluconeogênese/genética , Jejuno/cirurgia , Fígado/metabolismo , Estômago/cirurgia , Anastomose Cirúrgica , Animais , Peso Corporal , Diabetes Mellitus Tipo 2/metabolismo , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 2/metabolismo , Glucose-6-Fosfatase/genética , Glucose-6-Fosfatase/metabolismo , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Jejuno/metabolismo , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , RNA Mensageiro/metabolismo , RatosRESUMO
Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.
Assuntos
Carcinoma/genética , Proteínas de Ciclo Celular/genética , Ciclo Celular/genética , Proliferação de Células/genética , Neoplasias da Glândula Tireoide/genética , Idoso , Animais , Apoptose/genética , Carcinoma/patologia , Carcinoma Papilar , Proteínas de Ciclo Celular/biossíntese , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Thyroid cancer is the most common malignancy of endocrine system, and papillary thyroid cancer (PTC) is the most common subtype. E2F8, a novel identified E2F family member, was reported to associate with progression of several human cancers, however, its clinical significance and biological role in PTC remain unknown. METHODS: E2F8 or miR-144 expression profiles in PTC tissues were obtained from The Cancer Genome Atlas (TCGA) datasets, and the correlation of E2F8 expression with clinicopathological features was analyzed in a cohort PTC patients. The effects of E2F8 and miR-144 on proliferation were evaluated both in vitro and in vivo. Luciferase reporter assay was used to determine E2F8 was a direct target of miR-144. RESULTS: E2F8 was widely upregulated in PTC tissues, and overexpression of E2F8 was correlated with more aggressive clinicopathological features. In contrast, we found that silence of E2F8 significantly suppressed proliferation of PTC cells by inducing G1-phase arrest via downregulating Cyclin D1 (CCND1) both in vitro and in vivo. We also identified miR-144 as a tumor-suppressive microRNA that directly targeted E2F8 to inhibit proliferation of PTC cells in vitro and in vivo. Moreover, miR-144 was widely downregulated in PTC, where its expression correlated inversely with E2F8 expression. CONCLUSIONS: Our results demonstrate a new miR-144/E2F8/CCND1 regulatory axis controlling PTC development, which may offer a potential prognostic and therapeutic strategy. TRIAL REGISTRATION: No applicable.
Assuntos
Carcinoma Papilar/patologia , MicroRNAs/genética , Proteínas Repressoras/genética , Neoplasias da Glândula Tireoide/patologia , Regulação para Cima , Regiões 3' não Traduzidas , Animais , Carcinoma Papilar/genética , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Bases de Dados Genéticas , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Transplante de Neoplasias , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/genéticaRESUMO
Objective. The aim of our study was to explore the dependent condition of the relationship between uric acid and blood glucose in type 2 diabetes. Research Design and Methods. We measured the HbA1c, serum uric acid, creatinine, lipids profiles, and so forth of 605 newly diagnosed type 2 diabetes patients, and oral glucose tolerance tests (OGTTs) were performed on each patient. The population was divided into high and low insulin groups. Multiple linear regression analyses were conducted to assess the relationship between uric acid and HbA1c. Results. Serum uric acid and HbA1c levels were low in newly diagnosed type 2 diabetes patients. However, we found no significant relationship between uric acid and HbA1c by regression analysis after adjusting total insulin. The concentration of uric acid was inversely correlated with HbA1c in the high insulin group, regardless of patient sex. However, no associations were found in low insulin group. Conclusions. The negative correlation between uric acid and HbA1c is conditional in newly diagnosed type 2 diabetes patients and is related to hyperinsulinemia. Therefore, uric acid is likely only useful as a biomarker of blood glucose in patients exhibiting hyperinsulinemia.