Friend and foe: ß-cell Ca2+ signaling and the development of diabetes.
Mol Metab
; 21: 1-12, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30630689
ABSTRACT
BACKGROUND:
The divalent cation Calcium (Ca2+) regulates a wide range of processes in disparate cell types. Within insulin-producing ß-cells, increases in cytosolic Ca2+ directly stimulate insulin vesicle exocytosis, but also initiate multiple signaling pathways. Mediated through activation of downstream kinases and transcription factors, Ca2+-regulated signaling pathways leverage substantial influence on a number of critical cellular processes within the ß-cell. Additionally, there is evidence that prolonged activation of these same pathways is detrimental to ß-cell health and may contribute to Type 2 Diabetes pathogenesis. SCOPE OF REVIEW This review aims to briefly highlight canonical Ca2+ signaling pathways in ß-cells and how ß-cells regulate the movement of Ca2+ across numerous organelles and microdomains. As a main focus, this review synthesizes experimental data from in vitro and in vivo models on both the beneficial and detrimental effects of Ca2+ signaling pathways for ß-cell function and health. MAJORCONCLUSIONS:
Acute increases in intracellular Ca2+ stimulate a number of signaling cascades, resulting in (de-)phosphorylation events and activation of downstream transcription factors. The short-term stimulation of these Ca2+ signaling pathways promotes numerous cellular processes critical to ß-cell function, including increased viability, replication, and insulin production and secretion. Conversely, chronic stimulation of Ca2+ signaling pathways increases ß-cell ER stress and results in the loss of ß-cell differentiation status. Together, decades of study demonstrate that Ca2+ movement is tightly regulated within the ß-cell, which is at least partially due to its dual roles as a potent signaling molecule.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article