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J Clin Endocrinol Metab ; 98(5): 2053-61, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23539729

RESUMO

CONTEXT: A decrease in pancreatic ß-cell mass is involved in the development of type 2 diabetes. OBJECTIVE: The purpose of this study was to evaluate the ß-cell mass and the incidence of ß-cell neogenesis, replication, and apoptosis at both the prediabetic and diabetic stages. METHODS: We conducted a cross-sectional study of pancreatic tissues obtained from 42 patients undergoing a pancreatectomy who were classified into 4 groups: normal glucose tolerance (n = 11), impaired glucose tolerance (n = 11), newly diagnosed diabetes (n = 10), and long-standing type 2 diabetes (n = 10). RESULTS: The relative ß-cell area decreased and the ß-cell apoptosis increased during the development of diabetes. The number of single and clustered ß-cells, some of which coexpressed nestin, increased in the patients with impaired glucose tolerance and newly diagnosed diabetes. The prevalence of cells positive for both insulin and glucagon or somatostatin also increased in these patients compared with those with normal glucose tolerance. These double-positive cells were mainly localized in single and clustered ß-cells, rather than large islets, and were also positive for Pdx1 or Ngn3. The percentage of insulin-positive cells embedded within ducts increased in the impaired glucose tolerance group. There were no significant differences in the incidence of cells positive for both insulin and Ki67 among the groups. CONCLUSIONS: These results suggest that ß-cell neogenesis, rather than replication, predominates during impaired glucose tolerance and newly diagnosed diabetes in humans and may serve as a compensatory mechanism for the decreased ß-cell mass.


Assuntos
Apoptose , Proliferação de Células , Diabetes Mellitus Tipo 2/patologia , Intolerância à Glucose/patologia , Células Secretoras de Insulina/fisiologia , Estado Pré-Diabético/patologia , Regeneração , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Progressão da Doença , Feminino , Intolerância à Glucose/metabolismo , Intolerância à Glucose/fisiopatologia , Proteínas de Homeodomínio/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Proteínas de Filamentos Intermediários/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Nestina , Pâncreas/metabolismo , Pâncreas/patologia , Pâncreas/fisiopatologia , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/fisiopatologia , Transativadores/metabolismo
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