RESUMO
Mexico is a megadiverse country that has 3,600 to 4,000 species of medicinal plants, of which approximately 800 are used to treat conditions related to diabetes mellitus (DM). DM is a chronic degenerative disease of energy metabolism that exists as two types: type 1 (DM1) and type 2 (DM2). DM is considered a public health problem that affects 7% of the Mexican population older than 20 years. DM is clinically controlled with hypoglycaemic drugs, alpha-glucosidase inhibitors, insulin secretion stimulants or the direct application of insulin. The hypoglycaemic effectiveness of specific molecules has been determined only for some medicinal plants in Mexico used to treat DM2. The presence of molecules called glucokinins, wich are similar to animal insulin molecules, has been reported in some plant species; glucokinins act as both growth factors and regulators of glucose metabolism in plants. Therefore, we hypothesized that the hypoglycaemic effectiveness of some of the popularly used species for the control of DM could be due to the presence of glucokinin, as reported for Bauhinia variegata. The goal of this work was to use histochemistry to detect, the accumulation of protein that is immunocytochemically compatible with glucokinin in slide sections of hypoglycaemic species used as remedies for DM2. The top fourteen most used medicinal plants in Mexico were selected for study via microscopic sections. Proteins were histochemically detected using naphthol blue black and Johansen's quadruple stain, and the immunocytochemical correspondence of the proteins with glucokinin was investigated using an insulin antibody. All species studied reacted positively to proteins and glucokinin in the same structures. The presence of glucokinin in these structures and the corresponding hypoglycaemic effects are discussed in the contex of the actions of other compounds.
Assuntos
Hipoglicemiantes/isolamento & purificação , Plantas Medicinais/metabolismo , Animais , Anticorpos Anti-Insulina/metabolismo , México , Camundongos , Pâncreas/metabolismo , Estruturas Vegetais/metabolismo , Plantas Medicinais/química , Coloração e RotulagemRESUMO
OBJECTIVE: While it is known that there is progression to diabetes in <10 years in 70% of children with two or more islet autoantibodies, predictors of the progression to diabetes are only partially defined. RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study has observed 8,503 children who were at increased genetic risk for autoimmune diabetes. Insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and insulinoma-associated protein 2 autoantibodies (IA-2As) were measured every 3 months until 4 years of age and every 6 months thereafter; if results were positive, the autoantibodies were measured every 3 months. RESULTS: Life table analysis revealed that the cumulative incidence of diabetes by 5 years since the appearance of the first autoantibody differed significantly by the number of positive autoantibodies (47%, 36%, and 11%, respectively, in those with three autoantibodies, two autoantibodies, and one autoantibody, P < 0.001). In time-varying survival models adjusted for first-degree relative status, number of autoantibodies, age at first persistent confirmed autoantibodies, and HLA genotypes, higher mean IAA and IA-2A levels were associated with an increased risk of type 1 diabetes in children who were persistently autoantibody positive (IAAs: hazard ratio [HR] 8.1 [95% CI 4.6-14.2]; IA-2A: HR 7.4 [95% CI 4.3-12.6]; P < 0.0001]). The mean GADA level did not significantly affect the risk of diabetes. CONCLUSIONS: In the TEDDY study, children who have progressed to diabetes usually expressed two or more autoantibodies. Higher IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive.
Assuntos
Autoanticorpos/metabolismo , Diabetes Mellitus Tipo 1/imunologia , Anticorpos Anti-Insulina/metabolismo , Ilhotas Pancreáticas/imunologia , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/imunologia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Genótipo , Glutamato Descarboxilase/imunologia , Antígenos HLA-DQ/imunologia , Antígenos HLA-DR/imunologia , Humanos , Lactente , Masculino , Fatores de RiscoRESUMO
We can now predict the development of Type 1A (Immune Mediated) diabetes primarily through the determination of four biochemically characterized islet autoantibodies [insulin, GAD65, IA-2 (ICA512) and (Znt8)]. Prediction is possible because beta-cell destruction is chronically progressive and very slow in most, but not all individuals. We can also prevent type 1A diabetes in animal models and a major goal is the prevention of type 1A diabetes in man with multiple clinical trials underway.
Assuntos
Diabetes Mellitus Tipo 1/imunologia , Animais , Autoimunidade/imunologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Predisposição Genética para Doença/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Haplótipos , Humanos , Insulina/imunologia , Insulina/metabolismo , Anticorpos Anti-Insulina/imunologia , Anticorpos Anti-Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NODRESUMO
We can now predict the development of Type 1A (Immune Mediated) diabetes primarily through the determination of four biochemically characterized islet autoantibodies [insulin, GAD65, IA-2 (ICA512) and (Znt8)]. Prediction is possible because beta-cell destruction is chronically progressive and very slow in most, but not all individuals. We can also prevent type 1A diabetes in animal models and a major goal is the prevention of type 1A diabetes in man with multiple clinical trials underway.
Atualmente o desenvolvimento do diabetes melito tipo 1 A( imune mediado) pode ser predito através da determinação de quatro auto-anticorpos antiilhotas [antiinsulina, anti-GAD65, anti-IA2 (ICA512) e (anti-Znt8)] caracterizados bioquimicamente. A predição dessa doença é possível devido a destruição das células-beta, não em todos os indivíduos mas na sua maioria, ser crônica e lentamente progressiva. Também é possível prevenir o DM1 A em modelos animais e o objetivo maior é a prevenção dessa doença em humanos, para os quais vários protocolos clínicos estão em andamento.
Assuntos
Animais , Feminino , Humanos , Masculino , Camundongos , Diabetes Mellitus Tipo 1/imunologia , Autoimunidade/imunologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Predisposição Genética para Doença/genética , Haplótipos , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Anticorpos Anti-Insulina/imunologia , Anticorpos Anti-Insulina/metabolismo , Insulina/imunologia , Insulina/metabolismo , Camundongos Endogâmicos NODAssuntos
Complexo Antígeno-Anticorpo/análise , Diabetes Mellitus/sangue , Anticorpos Anti-Insulina/análise , Insulina/sangue , Adolescente , Adulto , Idoso , Sítios de Ligação de Anticorpos , Feminino , Humanos , Fragmentos de Imunoglobulinas/análise , Insulina/metabolismo , Anticorpos Anti-Insulina/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
El tamaño de los complejos inmunes insulina: antiinsulina (CII:A) presentes en el suero de pacientes diabéticos tratados con insulina, se estudió mediante su marcación con mono 125I-insulina y separación cromatográfica en columna de Sepharose CL-6B. Dicho tamaño se comparó con el título de anticuerpos antiinsulina y con la concentración total de insulina de esos sueros. Se identificaron dos tipos de CII:A cuyos tamaños, expresados como Kav, fueron de 0,41 ñ 0,002 y 0,32 ñ 0,01 (equivalentes a PMs de 170 y 300 Kd, rspectivamente), los que indicarían asociaciones anticuerpos: insulina del tipo 1:1 (1:2) y 2:1, respectivamente. Los complejos del tipo 2:1 se encontraron en sueros de bajo títulos de anticuerpos, mientras que a los 1:1 (o1:2) se los halló en sueros con títulos medianos y altos.
Assuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Complexo Antígeno-Anticorpo/análise , Diabetes Mellitus/sangue , Anticorpos Anti-Insulina/análise , Insulina/sangue , Sítios de Ligação de Anticorpos , Fragmentos de Imunoglobulinas/análise , Anticorpos Anti-Insulina/metabolismo , Insulina/metabolismoRESUMO
El tamaño de los complejos inmunes insulina: antiinsulina (CII:A) presentes en el suero de pacientes diabéticos tratados con insulina, se estudió mediante su marcación con mono 125I-insulina y separación cromatográfica en columna de Sepharose CL-6B. Dicho tamaño se comparó con el título de anticuerpos antiinsulina y con la concentración total de insulina de esos sueros. Se identificaron dos tipos de CII:A cuyos tamaños, expresados como Kav, fueron de 0,41 ñ 0,002 y 0,32 ñ 0,01 (equivalentes a PMs de 170 y 300 Kd, rspectivamente), los que indicarían asociaciones anticuerpos: insulina del tipo 1:1 (1:2) y 2:1, respectivamente. Los complejos del tipo 2:1 se encontraron en sueros de bajo títulos de anticuerpos, mientras que a los 1:1 (o1:2) se los halló en sueros con títulos medianos y altos.