Insulin hypersecretion in islets from diet-induced hyperinsulinemic obese female mice is associated with several functional adaptations in individual β-cells
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Título: | Insulin hypersecretion in islets from diet-induced hyperinsulinemic obese female mice is associated with several functional adaptations in individual β-cells |
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Autor/es: | González, Alejandro | Merino, Beatriz | Marroquí, Laura | Ñeco, Patricia | Alonso Magdalena, Paloma | Caballero Garrido, Ernesto | Vieira, Elaine | Soriano, Sergi | Gomis, Ramón | Nadal, Ángel | Quesada, Iván |
Grupo/s de investigación o GITE: | Fisiología de Membranas |
Centro, Departamento o Servicio: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Palabras clave: | Insulin | Hypersecretion | Hyperinsulinemic | Obese female mice | β-cells |
Área/s de conocimiento: | Fisiología |
Fecha de publicación: | oct-2013 |
Editor: | The Endocrine Society |
Cita bibliográfica: | Endocrinology. 2013, 154(10): 3515-3524. doi:10.1210/en.2013-1424 |
Resumen: | Insulin resistance and hyperinsulinemia are generally associated with obesity. Obese nondiabetic individuals develop a compensatory β-cell response to adjust insulin levels to the increased demand, maintaining euglycemia. Although several studies indicate that this compensation relies on structural changes, the existence of β-cell functional adaptations is incompletely understood. Here, we fed female mice with a high-fat diet (HFD) for 12 weeks. These animals became obese, hyperinsulinemic, insulin-resistant, and mildly glucose-intolerant while fed, and fasting glycemia was comparable in HFD and control mice. Islets from HFD animals exhibited increased β-cell mass and hypertrophy. Additionally, they had enhanced insulin gene expression and content and augmented glucose-induced insulin secretion. Electrophysiological examination of β-cells from both groups showed no differences in KATP channel open probability and conductance. However, action potentials elicited by glucose had larger amplitude in obese mice. Glucose-induced Ca2+ signals in intact islets, in isolated β-cells, and individual β-cells within islets were also increased in HFD mice. Additionally, a higher proportion of glucose-responsive cells was present in obese mice. In contrast, whole-cell Ca2+ current densities were similar in both groups. Capacitance measurements showed that depolarization-evoked exocytosis was enhanced in HFD β-cells compared with controls. Although this augment was not significant when capacitance increases of the whole β-cell population were normalized to cell size, the exocytotic output varied significantly when β-cells were distributed by size ranges. All these findings indicate that β-cell functional adaptations are present in the islet compensatory response to obesity. |
Patrocinador/es: | This work was supported by grants from the Ministerio de Ciencia e Innovación (BFU2010–21773; BFU2011–28358; SAF2010–19527), Generalitat Valenciana(PROMETEO/2011/080; ACOMP/2013/022), Generalitat de Catalunya (2009 SGR 1426) and European Foundation for the Study Diabetes (EFSD/BI Basic Programme). CIBERDEM is an initiative of the Instituto de Salud Carlos III. |
URI: | http://hdl.handle.net/10045/35326 |
ISSN: | 0013-7227 (Print) | 1945-7170 (Online) |
DOI: | 10.1210/en.2013-1424 |
Idioma: | eng |
Tipo: | info:eu-repo/semantics/article |
Derechos: | © 2014 The Endocrine Society |
Revisión científica: | si |
Versión del editor: | http://dx.doi.org/10.1210/en.2013-1424 |
Aparece en las colecciones: | INV - Fisiología de Membranas - Artículos de Revistas INV - FINE - Artículos de Revistas |
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