Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

XPR1 Mediates the Pancreatic beta-Cell Phosphate Flush

Texto completo
Autor(es):
Barker, Christopher J. [1] ; Tessaro, Fernando Henrique Galvao [1, 2] ; Ferreira, Sabrina de Souza [1, 2] ; Simas, Rafael [1] ; Ayala, Thais S. [1, 2] ; Kohler, Martin [1] ; Rajasekaran, Subu Surendran [1] ; Martins, Joilson O. [2] ; Dare, Elisabetta [1] ; Berggren, Per-Olof [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Stockholm - Sweden
[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Lab Immunoendocrinol, Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Diabetes; v. 70, n. 1, p. 111-118, JAN 2021.
Citações Web of Science: 1
Resumo

Glucose-stimulated insulin secretion is the hallmark of the pancreatic beta-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 (P-i) 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 beta-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 P-i 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 P-i efflux was stimulated by inositol pyrophosphates, and basal intracellular P-i 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. (AU)

Processo FAPESP: 17/11540-7 - Investigando o papel da insulina na vigência da inflamação alérgica pulmonar em camundongos diabéticos e sadios
Beneficiário:Joilson de Oliveira Martins
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 14/05214-1 - Investigando o papel da insulina em diferentes infecções em animais diabéticos e sadios
Beneficiário:Joilson de Oliveira Martins
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 10/02272-0 - Efeito da insulina na inflamação pulmonar secundária a sepse, na imunidade inata, na ativação do seu gene (BGK) e seus receptores (IR-A e IR-B)
Beneficiário:Joilson de Oliveira Martins
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores