Local and regional control of calcium dynamics in the pancreatic islet.
Diabetes Obes Metab
; 19 Suppl 1: 30-41, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28466490
ABSTRACT
Ca2+ is the key intracellular regulator of insulin secretion, acting in the ß-cell as the ultimate trigger for exocytosis. In response to high glucose, ATP-sensitive K+ channel closure and plasma membrane depolarization engage a sophisticated machinery to drive pulsatile cytosolic Ca2+ changes. Voltage-gated Ca2+ channels, Ca2+ -activated K+ channels and Na+ /Ca2+ exchange all play important roles. The use of targeted Ca2+ probes has revealed that during each cytosolic Ca2+ pulse, uptake of Ca2+ by mitochondria, endoplasmic reticulum (ER), secretory granules and lysosomes fine-tune cytosolic Ca2+ dynamics and control organellar function. For example, changes in the expression of the Ca2+ -binding protein Sorcin appear to provide a link between ER Ca2+ levels and ER stress, affecting ß-cell function and survival. Across the islet, intercellular communication between highly interconnected "hubs," which act as pacemaker ß-cells, and subservient "followers," ensures efficient insulin secretion. Loss of connectivity is seen after the deletion of genes associated with type 2 diabetes (T2D) and follows metabolic and inflammatory insults that characterize this disease. Hubs, which typically comprise ~1%-10% of total ß-cells, are repurposed for their specialized role by expression of high glucokinase (Gck) but lower Pdx1 and Nkx6.1 levels. Single cell-omics are poised to provide a deeper understanding of the nature of these cells and of the networks through which they communicate. New insights into the control of both the intra- and intercellular Ca2+ dynamics may thus shed light on T2D pathology and provide novel opportunities for therapy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comunicação Celular
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Ilhotas Pancreáticas
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Sinalização do Cálcio
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Modelos Biológicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article