Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.781
Filtrar
1.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(9): 1003-1008, 2019 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-31640950

RESUMO

OBJECTIVE: To compare islet ß-cell function in type 2 diabetic (T2DM) patients with different glycosylated hemoglobin (HbA1c) levels and diabetes durations. METHODS: We examined body parameters, biochemical profiles and islet autoantibodies in a total of 803 T2DM patients admitted in the Department of Endocrinology of the First Affiliated Hospital of Nanjing Medical University between December, 2014 and April, 2016. The patients were stratified by HbA1c level and disease course and underwent steamed bun test to evaluate islet ß-cell function and insulin resistance. RESULTS: Linear correlation analysis showed that in T2DM patients, HbA1c level was negatively correlated with HOMA2-IR, HOMA2-%ß, DI30 and DI180 (P=0.000), and disease course was negatively correlated with HOMA2-IR, HOMA2-% ß, and DI180 (P < 0.05). The patients with different HbA1c levels showed significantly different HOMA2-IR, HOMA2-%ß, DI30 and DI180 (P=0.000); HOMA2-%ß, DI30 and DI180 were significantly higher in patients with HbA1c levels < 7.8%, and HOMA2-% ß was significantly decreased in patients with HbA1c levels above 9.8%. The patients with different disease courses also had significant differences in HOMA2-IR, HOMA2-%ß, DI30, and DI180 (P=0.000), and as the disease course extended, DI30 and DI180 tended to decrease progressively. Multivariate linear regression analysis showed that HbA1c, diabetes duration, and body mass index (BMI) were all independent factors affecting islet ß- cell function in T2DM patients. CONCLUSIONS: The secretion function of islet ß cells decreases progressively with the increase of HbA1c level or disease course in T2DM patients, but the disease course does not appear to have an effect as strong as that of HbA1c level on islet ß cell function.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobina A Glicada/análise , Ilhotas Pancreáticas/patologia , Glicemia , Índice de Massa Corporal , Progressão da Doença , Humanos , Resistência à Insulina
2.
Georgian Med News ; (290): 144-149, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31322533

RESUMO

There have been presented the results of the histomorphological research of the effect of the beans' thick extract (BTE) on the state of the pancreas on the model of diabetes mellitus type 2 on the background of obesity in the rats in our research. The simulation of type 2 diabetes on the background of obesity in the animals has led to the development of signs of insulin's inhibition of insulin producing apparatus - some different expressions of dystrophy and degeneration of the ß-cells. The consequence of the hyperfunction has been exhaustion and even death of ß-cells, the development of the diabetic condition. The redistribution of pancreatic islet ß-content of cells has contributed to the increase of the small islands and had a compensatory nature. The treatment of the animals by the BTE has fully prevented an excessive negative impact on revenues of carbohydrates insulin producing apparatus, because it improves the morphological status of ß-cells, reduces the part of small pancreatic islets, almost restores medium and large islets to the level of the «Intact control¼ group. The comparison drug - metformin - has a positive effect on the morphological status of the pancreatic ß-cells, but this effect is obviously not enough for improving or restoring the normal % of distribution of islets.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/terapia , Hipoglicemiantes/uso terapêutico , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Obesidade/complicações , Extratos Vegetais/uso terapêutico , Sementes/química , Animais , Tamanho Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Metformina/administração & dosagem , Extratos Vegetais/química , Ratos , Açúcares
3.
DNA Cell Biol ; 38(10): 1069-1077, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31361511

RESUMO

Long-noncoding RNA AC092159.2, located ∼247 bp upstream of the TMEM18 gene, may play integral roles in metabolic processes, including adipocyte differentiation and glycometabolism. AC092159.2 may be an important regulator of TMEM18, which is an important susceptibility gene related to obesity and type 2 diabetes. We designed a case-control study (including 964 gestational diabetes mellitus [GDM] cases and 1021 controls) to assess the associations of 14 single-nucleotide polymorphisms (SNPs) in AC092159.2 with the GDM risk. Logistic regression analyses showed that rs11127496 A > G, rs12714417 C > T, and rs1320334 A > G conferred a decreased GDM risk in the recessive and additive model, whereas rs11691220 T > C conferred an increased GDM risk in the dominant and additive model. Also, with increasing number of protective alleles of the four SNPs, the risk of GDM was significantly decreased in a dose-dependent manner (ptrend = 0.007). Further function annotation indicated that these four SNPs may fall on the function elements of human pancreatic islets. The genotype-phenotype associations suggested that these SNPs may contribute to GDM by affecting TMEM18 expression. AC092159.2 SNPs (rs11127496 A > G, rs11691220 T > C, rs12714417 C > T, and rs1320334 A > G) may be susceptibility makers for risk of GDM in Chinese females.


Assuntos
Diabetes Gestacional/genética , Ilhotas Pancreáticas/metabolismo , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/etnologia , Diabetes Gestacional/patologia , Feminino , Regulação da Expressão Gênica , Estudos de Associação Genética , Humanos , Ilhotas Pancreáticas/patologia , Proteínas de Membrana/metabolismo , Modelos Genéticos , Gravidez , RNA Longo não Codificante/metabolismo , Risco
4.
Transplant Proc ; 51(5): 1451-1457, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31079939

RESUMO

BACKGROUND: Quercetin (QE) is an antioxidant, anti-inflammatory, flavonoid compound. It was shown that islets are susceptible to oxidative stress due to their inherent low antioxidant capacity. In the present study, we investigated whether treatment of mouse islets with QE could enhance their function before transplantation. METHODS: Balb/c mouse islets were treated with various concentrations of QE and their viability, function, and nitric oxide (NO) and the expression of inducible NO synthase (iNOS) were determined before and after cytokine treatment. The expression of antioxidant genes was determined. Apoptosis and apoptosis-associated gene expression was measured using INS-1 cells with or without QE treatment before and after cytokine treatment. RESULTS: The QE-treated islets and INS-1 cells showed higher cell function compared to untreated control. The expression of heme oxygenase-1, manganese-dependent superoxide dismutase, and B-cell lymphoma-2 (Bcl-2) were enhanced, and the expression of NO, iNOS, and Bcl-2-associated X protein were reduced before and after cytokine treatment. CONCLUSIONS: Our results show that QE could enhance the viability and reduce apoptosis of mouse islets and improve their function before transplantation.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas/efeitos dos fármacos , Quercetina/farmacologia , Animais , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos
5.
Nutrients ; 11(4)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987324

RESUMO

Alcalase- generated potato protein hydrolysate (APPH) is a potential bioactive peptide against diabetes mellitus (DM) and DM-associated secondary effects in animal models. The aim of the present study was to find the efficiency of a deca-peptide DIKTNKPVIF (DF) from APPH against DM. Six-week-old male ICR mice were divided into the following groups: Control, Control+DF (received 50 mg/kg DF), streptozotocin (STZ)-induced DM group, DM+Acarbose group (20 mg/kg of acarbose), DM+DF-L (25 mg/kg of DF), DM+DF-H (50 mg/kg of DF), and DM+APPH (50 mg/kg of APPH). Comparable to APPH, treatment with DF effectively regulated blood glucose level and also controlled plasma total glycerol (TG), total cholesterol (TC), insulin, and HbA1c levels in DM animals. DF treatment also showed evidence of ameliorating DM-associated damages in the pancreatic islets and in the liver, heart, and kidney tissues. Therefore, the results demonstrate that the short synthetic peptide-DF may effectively provide protection against DM-associated damages.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/prevenção & controle , Hipoglicemiantes/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Oligopeptídeos/farmacologia , Proteínas de Plantas/metabolismo , Hidrolisados de Proteína/metabolismo , Solanum tuberosum/metabolismo , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Hemoglobina A Glicada/metabolismo , Hipoglicemiantes/metabolismo , Insulina/sangue , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos ICR , Oligopeptídeos/metabolismo , Estreptozocina , Subtilisinas/metabolismo
7.
Dokl Biol Sci ; 484(1): 1-4, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31016494

RESUMO

T1R3 protein, the main subunit of the sweet taste receptor and receptor of amino acid taste, is expressed in the epithelium of the tongue and gastrointestinal tract, in ß cells of the pancreas, hypothalamus, and numerous other organs. Recently, convincing evidences on the involvement of T1R3 in the control of carbohydrate and lipid metabolism, and the control of incretin and insulin production were obtained. In the study on Tas1r3-gene knockout mouse strain and parent C57BL/6J strain as a control, the data on the effect of T1R3 on morphological characteristics of Langerhans islets in the pancreas were obtained. In Tas1r3 knockout animals, we found a reduction in the size of islets and their density in pancreatic tissue as compared to the parent strain. In addition, a decrease in the expression of active caspase-3 in the islets of gene-knockout mice was demonstrated. The data obtained indicate that the lack of functioning gene encoding sweet taste receptor protein causes a dystrophy of the islet tissue and is associated with the development of pathological changes in the pancreas specific to type 2 diabetes mellitus and obesity in humans.


Assuntos
Ilhotas Pancreáticas/metabolismo , Receptores Acoplados a Proteínas-G/genética , Animais , Caspase 3/genética , Caspase 3/metabolismo , Deleção de Genes , Ilhotas Pancreáticas/crescimento & desenvolvimento , Ilhotas Pancreáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas-G/metabolismo
8.
Nature ; 567(7746): 43-48, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30760930

RESUMO

Cell-identity switches, in which terminally differentiated cells are converted into different cell types when stressed, represent a widespread regenerative strategy in animals, yet they are poorly documented in mammals. In mice, some glucagon-producing pancreatic α-cells and somatostatin-producing δ-cells become insulin-expressing cells after the ablation of insulin-secreting ß-cells, thus promoting diabetes recovery. Whether human islets also display this plasticity, especially in diabetic conditions, remains unknown. Here we show that islet non-ß-cells, namely α-cells and pancreatic polypeptide (PPY)-producing γ-cells, obtained from deceased non-diabetic or diabetic human donors, can be lineage-traced and reprogrammed by the transcription factors PDX1 and MAFA to produce and secrete insulin in response to glucose. When transplanted into diabetic mice, converted human α-cells reverse diabetes and continue to produce insulin even after six months. Notably, insulin-producing α-cells maintain expression of α-cell markers, as seen by deep transcriptomic and proteomic characterization. These observations provide conceptual evidence and a molecular framework for a mechanistic understanding of in situ cell plasticity as a treatment for diabetes and other degenerative diseases.


Assuntos
Diabetes Mellitus/patologia , Diabetes Mellitus/terapia , Células Secretoras de Glucagon/citologia , Células Secretoras de Glucagon/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/patologia , Animais , Biomarcadores/análise , Linhagem da Célula/efeitos dos fármacos , Reprogramação Celular/efeitos dos fármacos , Diabetes Mellitus/imunologia , Diabetes Mellitus/metabolismo , Modelos Animais de Doenças , Feminino , Glucagon/metabolismo , Células Secretoras de Glucagon/efeitos dos fármacos , Células Secretoras de Glucagon/transplante , Glucose/farmacologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/metabolismo , Fatores de Transcrição Maf Maior/genética , Fatores de Transcrição Maf Maior/metabolismo , Masculino , Camundongos , Especificidade de Órgãos/efeitos dos fármacos , Polipeptídeo Pancreático/metabolismo , Células Secretoras de Polipeptídeo Pancreático/citologia , Células Secretoras de Polipeptídeo Pancreático/efeitos dos fármacos , Células Secretoras de Polipeptídeo Pancreático/metabolismo , Proteômica , Análise de Sequência de RNA , Transativadores/genética , Transativadores/metabolismo , Transcriptoma , Transdução Genética
9.
J Med Food ; 22(2): 196-201, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30730805

RESUMO

Malva verticillata (Chinese mallow) has long been used in traditional medicines and herbal teas in Asia. The n-BuOH fraction (Fr) from M. verticillata promoted significant recovery of alloxan-damaged (AXD) pancreatic islets (PIs) in zebrafish (ZF). Two major components were isolated from M. verticillata through repeated-column chromatography. Based on several spectroscopic methods, including nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and fast atom bombardment-mass spectrometry (FAB-MS), the chemical structures of compounds 1 and 2 were determined. In addition, the quantity of both compounds in the n-BuOH Fr was investigated through high-performance liquid chromatography (HPLC) and the quantities of compounds 1 and 2 in the n-BuOH Fr were determined to be 5.58% ± 0.16% and 2.85% ± 0.13%, respectively. The n-BuOH Fr, compounds 1 and 2, and the mixture of compounds 1 and 2 (MX, 1 and 2, the ratio of both compounds in n-BuOH Fr, 1.96:1) were evaluated for their ability to recover AXD PIs and for their KATP channel-blocking mechanism using diazoxide in ZF. The n-BuOH Fr (10 µg/mL) and compounds 1 and MX (1 µg/mL) exhibited a recovery effect on AXD PIs. The n-BuOH Fr (10 µg/mL) and MX (1 µg/mL) were also confirmed to be useful KATP channel activators. A synergistic effect of MX in the recovery of AXD PIs was first confirmed in ZF, and it was discovered that 2 acted as an insulin sensitivity activator that increased the activity of compound 1.


Assuntos
Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Malva/química , Pancreatopatias , Extratos Vegetais/farmacologia , Aloxano , Animais , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Sinergismo Farmacológico , Resistência à Insulina , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Canais KATP/metabolismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Pancreatopatias/induzido quimicamente , Pancreatopatias/metabolismo , Pancreatopatias/patologia , Fitoterapia , Extratos Vegetais/química , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Infravermelho , Peixe-Zebra
12.
Int J Nanomedicine ; 14: 339-351, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30655667

RESUMO

Background: Hepatic ischemia/reperfusion-induced pancreatic islet injury (HI/RIPII) was an important pathophysiological phenomenon in clinics. In the present study, we observed the effects of phycocyanin on HI/RIPII. However, the half-life of phycocyanin was extremely short and limited its use in vivo. Materials and methods: In order to overcome this shortcoming, poly(ethylene glycol)-b-(poly(l-glutamic acid)-g-polyethylenimine) (PEG-b-(PG-g-PEI)) was synthesized and estimated as a nanocarrier for lengthening delivery of phycocyanin through the abdominal subcutaneous injection in rats. Phycocyanin (isoelectric point=4.3) was encapsulated with PEG-b-(PG-g-PEI) via electrostatic interactions at pH 7.4. Results: In vitro phycocyanin was fast and efficiently encapsulated and showing efficient loading and sustained release. In vivo the anti-HI/RIPII function of phycocyanin/PEG-b-(PG-g-PEI) complex was surveyed in rats using free phycocyanin as the controls, and the results showed that phycocyanin/PEG-b-(PG-g-PEI) complex reduced HI/RIPII property and enlarged islet functionality. Conclusion: These results suggested that PEG-b-(PG-g-PEI) might be treated as a potential phycocyanin nanocarrier.


Assuntos
Ilhotas Pancreáticas/lesões , Ficocianina/uso terapêutico , Polietilenoglicóis/química , Polietilenoimina/análogos & derivados , Ácido Poliglutâmico/análogos & derivados , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Alanina Transaminase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Metabolismo Basal , Glicemia/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Insulina/sangue , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Fígado/efeitos dos fármacos , Fígado/lesões , Fígado/patologia , Malondialdeído/metabolismo , Ficocianina/química , Ficocianina/farmacologia , Polietilenoimina/química , Ácido Poliglutâmico/química , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/sangue , Superóxido Dismutase/metabolismo
14.
Methods Mol Biol ; 1916: 49-65, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30535681

RESUMO

In 1976, an animal model of type 2 diabetes (T2DM) was described by Cameron et al. using injection of monosodium glutamate (MSG) in KK mice during the neonatal period. Some years later, similar models have been developed by various doses and durations and the main of these models exhibited obesity and features of diabetes mellitus, including glycosuria, hyperglycemia, hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. Studies indicated that MSG treatment of newborn animals generates necrosis of neuronal cells of the hypothalamic ventromedial nucleus and arcuate nucleus. Neonatal MSG-treatment was related to normoglycemic-normoinsulinemic state at young ages and development of obesity and hyperinsulinemia at adult ages. Following observation of a severe hypertrophy of pancreatic islets due to the proliferation of ß-cells in MSG-treated mice, this model has been proposed as a useful animal model of human T2DM. A higher dose of MSG (≥4 mg/g body weight) accompanied by a longer follow-up duration (>6 months) are needed to establish a typical animal model of T2DM.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Hiperinsulinismo/patologia , Ilhotas Pancreáticas/patologia , Obesidade/patologia , Animais , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Humanos , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/metabolismo , Resistência à Insulina/genética , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/patologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Obesidade/induzido quimicamente , Obesidade/metabolismo , Glutamato de Sódio/toxicidade
15.
Methods Mol Biol ; 1916: 213-222, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30535698

RESUMO

This chapter describes the propagation and characterization of transplantable insulinoma cells as model of insulin-producing pancreatic islet cells in the rat. Here, the cells are propagated by transplantation into rats followed by harvesting after growth for approximately 1 month. The cells are then purified by Percoll density gradient centrifugation and characterized by pulse-chase radiolabelling and immunoprecipitation of the insulin-related peptides. The results show that the transplantable insulinoma cells produce insulin in a manner similar to that found in normal pancreatic islets.


Assuntos
Técnicas de Cultura de Células/métodos , Imunoprecipitação/métodos , Insulinoma/patologia , Neoplasias Pancreáticas/genética , Animais , Proliferação de Células/genética , Humanos , Insulina/genética , Secreção de Insulina/genética , Insulinoma/genética , Ilhotas Pancreáticas/crescimento & desenvolvimento , Ilhotas Pancreáticas/patologia , Neoplasias Pancreáticas/patologia , Ratos
16.
Methods Mol Biol ; 1916: 223-232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30535699

RESUMO

The islets of Langerhans release vital hormones involved in the regulation of blood sugar and other aspects of metabolism. The islets are housed in diffuse clusters of cells within the exocrine pancreas and, therefore, purification of these cells for research or transplant purposes is a difficult undertaking. Here, a detailed protocol is presented for purification of islets from rat pancreas using limited collagenase digestion and step gradient centrifugation techniques. In addition, a method for assessing islet viability is presented using perifusion under both basal and stimulatory glucose conditions, with measurement of the hormone released using an immunoassay for insulin.


Assuntos
Separação Celular/métodos , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas/ultraestrutura , Pâncreas/metabolismo , Animais , Glucose/metabolismo , Humanos , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Pâncreas/patologia , Ratos
17.
Front Immunol ; 9: 2800, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555479

RESUMO

Diabetogenic T cells infiltrate the pancreatic islets by transmigrating across the microcapillaries residing close to, or within, the pancreatic islets. Deficiency in IFNγ signaling prevents efficient migration of T cells into the pancreatic islets, but the IFNγ-regulated molecules that mediate this are uncertain. Homing of autoreactive T cells into target tissues may require antigen specificity through presentation of cognate antigen by MHC expressed on the vascular endothelium. We investigated the hypothesis that IFNγ promotes the migration of islet antigen-specific CD4+ T cells by upregulating MHC class II on islet endothelial cells (IEC), thereby providing an antigen-specific signal for islet infiltration. Upon IFNγ stimulation, MHC class II, which is not constitutively expressed on IEC, was induced. IFNγ-dependent upregulation of MHC class II was detected in IEC isolated from prediabetic NOD mice at the earliest stages of insulitis, before other markers of inflammation were present. Using a CD4+ T cell-mediated adoptive transfer model of autoimmune diabetes we observed that even though diabetes does not develop in recipient mice lacking IFNγ receptors, mice with MHC class II-deficient IEC were not protected from disease. Thus, IFNγ-regulated molecules, but not MHC class II or antigen presentation by IECs is required for the early migration of antigen-specific CD4+ T cells into the pancreatic islets.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Células Endoteliais/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Interferon gama/imunologia , Ilhotas Pancreáticas/imunologia , Estado Pré-Diabético/imunologia , Animais , Biomarcadores , Linfócitos T CD4-Positivos/patologia , Células Endoteliais/patologia , Regulação da Expressão Gênica/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Interferon gama/genética , Ilhotas Pancreáticas/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Estado Pré-Diabético/genética , Estado Pré-Diabético/patologia
18.
J Biosci ; 43(5): 921-929, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30541952

RESUMO

5rolGLP-HV is a promising dual-function peptide for the treatment of diabetes and thrombosis simultaneously. For investigating the therapeutic mechanism of 5rolGLP-HV for type 2 diabetes mellitus (T2DM), STZ-induced diabetic mice were established and treated with 5rolGLP-HV. The results showed that daily water and food intake, blood glucose, serum and pancreatic insulin levels significantly decreased after 5rolGLP-HV treatment with various oral concentrations, and 16 mg/kg was the optimal dose for controlling diabetes. 5rolGLP-HV treatment decreased the MDA levels and the T-SOD activity in serum and pancreatic of diabetic mice (but not up to significant difference), and significantly increased the expression of signal pathways related genes of rolGLP-1, also the density of insulin expression and the numbers of apoptosis cells in islets of diabetic mice were significantly decreased in comparison to the negative diabetic mice. These effects above may be clarified the hypoglycemic mechanisms of 5rolGLP-HV, and 5rolGLP-HV may be as a potential drug for diabetes in future.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Hipoglicemiantes/farmacologia , Insulina/sangue , Proteínas Recombinantes/farmacologia , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Ingestão de Líquidos/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ingestão de Alimentos/efeitos dos fármacos , Regulação da Expressão Gênica , Peptídeo 1 Semelhante ao Glucagon/biossíntese , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hirudinas/química , Hipoglicemiantes/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Masculino , Malondialdeído/antagonistas & inibidores , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Recombinantes/biossíntese , Estreptozocina , Superóxido Dismutase/metabolismo
19.
J. physiol. biochem ; 74(4): 667-677, nov. 2018. graf, ilus, tab
Artigo em Inglês | IBECS | ID: ibc-179044

RESUMO

The adrenomedullary chromaffin cells' hormonal pathway has been related to the pathophysiology of diabetes mellitus. In mice, the deletion of insulin receptor substrate type 2 (Irs2) causes peripheral insulin resistance and reduction in Beta-cell mass, leading to overt diabetes, with gender differences on adrenergic signaling. To further unravel the relevance of Irs2 on glycemic control, we analyzed in adult Irs2 deficient (Irs2-/-) mice, of both sexes but still normoglycemic, dopamine effects on insulin secretion and glycerol release, as well as their adrenal medulla by an immunohistochemical and morphologic approach. In isolated islets, 10 μM dopamine significantly inhibited insulin release in wild-type (WT) and female Irs2−/− mice; however, male Irs2−/− islets were insensitive to that catecholamine. Similarly, on isolated adipocytes, gender differences were observed between WT and Irs2-/- mice in basal and evoked glycerol release with crescent concentrations of dopamine. By immunohistochemistry, reactivity to tyrosine hydroxylase (TH) in female mice was significantly higher in the adrenal medulla of Irs2-/- compared to WT; although no differences for TH-immunopositivity were observed between the male groups of mice. However, compared to their corresponding WT animals, adrenomedullary chromaffin cells of Irs2-/- mice showed a significant decrease in the cellular and nuclear areas, and even in their percentage of apoptosis. Therefore, our observations suggest that, together with gender differences on dopamine responses in Irs2-/- mice, disturbances in adrenomedullary chromaffin cells could be related to deficiency of Irs2. Accordingly, Irs2 could be necessary for adequate glucose homeostasis and maintenance of the population of the adrenomedullary chromaffin cells


No disponible


Assuntos
Animais , Masculino , Feminino , Camundongos , Medula Suprarrenal/metabolismo , Dopamina/metabolismo , Hiperinsulinismo/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Estado Pré-Diabético/metabolismo , Adipócitos Brancos , Hiperinsulinismo/sangue , Hiperinsulinismo/patologia , Técnicas In Vitro , Proteínas Substratos do Receptor de Insulina/genética , Ilhotas Pancreáticas/patologia , Estado Pré-Diabético/patologia
20.
Diabetes ; 67(9): 1807-1815, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30084829

RESUMO

Type 2 diabetes mellitus (T2DM) is characterized by the inability of the insulin-producing ß-cells to overcome insulin resistance. We previously identified an imprinted region on chromosome 14, the DLK1-MEG3 locus, as being downregulated in islets from humans with T2DM. In this study, using targeted epigenetic modifiers, we prove that increased methylation at the promoter of Meg3 in mouse ßTC6 ß-cells results in decreased transcription of the maternal transcripts associated with this locus. As a result, the sensitivity of ß-cells to cytokine-mediated oxidative stress was increased. Additionally, we demonstrate that an evolutionarily conserved intronic region at the MEG3 locus can function as an enhancer in ßTC6 ß-cells. Using circular chromosome conformation capture followed by high-throughput sequencing, we demonstrate that the promoter of MEG3 physically interacts with this novel enhancer and other putative regulatory elements in this imprinted region in human islets. Remarkably, this enhancer is bound in an allele-specific manner by the transcription factors FOXA2, PDX1, and NKX2.2. Overall, these data suggest that the intronic MEG3 enhancer plays an important role in the regulation of allele-specific expression at the imprinted DLK1-MEG3 locus in human ß-cells, which in turn impacts the sensitivity of ß-cells to cytokine-mediated oxidative stress.


Assuntos
Metilação de DNA , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Ilhotas Pancreáticas/metabolismo , Proteínas de Membrana/metabolismo , Regiões Promotoras Genéticas , RNA Longo não Codificante/metabolismo , Animais , Linhagem Celular , Citocinas/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/química , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Diabetes Mellitus Tipo 2/patologia , Elementos Facilitadores Genéticos , Epigênese Genética , Loci Gênicos , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Homeodomínio/química , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Ilhotas Pancreáticas/patologia , Região de Controle de Locus Gênico , Proteínas de Membrana/genética , Camundongos , Mutação , Estresse Oxidativo/efeitos dos fármacos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/química , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Bancos de Tecidos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA