Your browser doesn't support javascript.
loading
XPR1 Mediates the Pancreatic ß-Cell Phosphate Flush.
Barker, Christopher J; Tessaro, Fernando Henrique Galvão; Ferreira, Sabrina de Souza; Simas, Rafael; Ayala, Thais S; Köhler, Martin; Rajasekaran, Subu Surendran; Martins, Joilson O; Darè, Elisabetta; Berggren, Per-Olof.
Afiliação
  • Barker CJ; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden chris.barker@ki.se per-olof.berggren@ki.se.
  • Tessaro FHG; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
  • Ferreira SS; Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University São Paulo, São Paulo, Brazil.
  • Simas R; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
  • Ayala TS; Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University São Paulo, São Paulo, Brazil.
  • Köhler M; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
  • Rajasekaran SS; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
  • Martins JO; Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University São Paulo, São Paulo, Brazil.
  • Darè E; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
  • Berggren PO; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
Diabetes ; 70(1): 111-118, 2021 01.
Article em En | MEDLINE | ID: mdl-32826297
ABSTRACT
Glucose-stimulated insulin secretion is the hallmark of the pancreatic ß-cell, a critical player in the regulation of blood glucose concentration. In 1974, the remarkable observation was made that an efflux of intracellular inorganic phosphate (Pi) accompanied the events of stimulated insulin secretion. The mechanism behind this "phosphate flush," its association with insulin secretion, and its regulation have since then remained a mystery. We recapitulated the phosphate flush in the MIN6m9 ß-cell line and pseudoislets. We demonstrated that knockdown of XPR1, a phosphate transporter present in MIN6m9 cells and pancreatic islets, prevented this flush. Concomitantly, XPR1 silencing led to intracellular Pi accumulation and a potential impact on Ca2+ signaling. XPR1 knockdown slightly blunted first-phase glucose-stimulated insulin secretion in MIN6m9 cells, but had no significant impact on pseudoislet secretion. In keeping with other cell types, basal Pi efflux was stimulated by inositol pyrophosphates, and basal intracellular Pi accumulated following knockdown of inositol hexakisphosphate kinases. However, the glucose-driven phosphate flush occurred despite inositol pyrophosphate depletion. Finally, while it is unlikely that XPR1 directly affects exocytosis, it may protect Ca2+ signaling. Thus, we have revealed XPR1 as the missing mediator of the phosphate flush, shedding light on a 45-year-old mystery.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfatos / Receptores Virais / Receptores Acoplados a Proteínas G / Células Secretoras de Insulina / Secreção de Insulina Limite: Animals Idioma: En Revista: Diabetes Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfatos / Receptores Virais / Receptores Acoplados a Proteínas G / Células Secretoras de Insulina / Secreção de Insulina Limite: Animals Idioma: En Revista: Diabetes Ano de publicação: 2021 Tipo de documento: Article