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Dimensionality and size scaling of coordinated Ca(2+) dynamics in MIN6 ß-cell clusters.
Hraha, Thomas H; Bernard, Abigail B; Nguyen, Linda M; Anseth, Kristi S; Benninger, Richard K P.
Afiliação
  • Hraha TH; Department of Bioengineering, University of Colorado, Anschutz Medical campus, Aurora, CO.
  • Bernard AB; Department of Biological and Chemical Engineering and the Howard Hughes Medical Institute, University of Colorado, Boulder, CO.
  • Nguyen LM; Department of Bioengineering, University of Colorado, Anschutz Medical campus, Aurora, CO.
  • Anseth KS; Department of Biological and Chemical Engineering and the Howard Hughes Medical Institute, University of Colorado, Boulder, CO.
  • Benninger RK; Department of Bioengineering, University of Colorado, Anschutz Medical campus, Aurora, CO; Barbara Davis Center for Childhood Diabetes, University of Colorado, Anschutz Medical Campus, Aurora, CO. Electronic address: richard.benninger@ucdenver.edu.
Biophys J ; 106(1): 299-309, 2014 Jan 07.
Article em En | MEDLINE | ID: mdl-24411262
Pancreatic islets of Langerhans regulate blood glucose homeostasis by the secretion of the hormone insulin. Like many neuroendocrine cells, the coupling between insulin-secreting ß-cells in the islet is critical for the dynamics of hormone secretion. We have examined how this coupling architecture regulates the electrical dynamics that underlie insulin secretion by utilizing a microwell-based aggregation method to generate clusters of a ß-cell line with defined sizes and dimensions. We measured the dynamics of free-calcium activity ([Ca(2+)]i) and insulin secretion and compared these measurements with a percolating network model. We observed that the coupling dimension was critical for regulating [Ca(2+)]i dynamics and insulin secretion. Three-dimensional coupling led to size-invariant suppression of [Ca(2+)]i at low glucose and robust synchronized [Ca(2+)]i oscillations at elevated glucose, whereas two-dimensional coupling showed poor suppression and less robust synchronization, with significant size-dependence. The dimension- and size-scaling of [Ca(2+)]i at high and low glucose could be accurately described with the percolating network model, using similar network connectivity. As such this could explain the fundamentally different behavior and size-scaling observed under each coupling dimension. This study highlights the dependence of proper ß-cell function on the coupling architecture that will be important for developing therapeutic treatments for diabetes such as islet transplantation techniques. Furthermore, this will be vital to gain a better understanding of the general features by which cellular interactions regulate coupled multicellular systems.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cálcio / Sinalização do Cálcio / Células Secretoras de Insulina Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Biophys J Ano de publicação: 2014 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cálcio / Sinalização do Cálcio / Células Secretoras de Insulina Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Biophys J Ano de publicação: 2014 Tipo de documento: Article País de publicação: Estados Unidos