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@article{Rutter:2017:10.1111/dom.12990,
author = {Rutter, GA and Hodson, DJ and Chabosseau, P and Haythorne, E and Pullen, TJ and Leclerc, I},
doi = {10.1111/dom.12990},
journal = {Diabetes, Obesity and Metabolism},
pages = {30--41},
title = {Local and regional control of calcium dynamics in the pancreatic islet},
url = {http://dx.doi.org/10.1111/dom.12990},
volume = {19},
year = {2017}
}

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TY  - JOUR
AB  - Ca2+ is the key intracellular regulator of insulin secretion, acting in the β-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 β-cell function and survival. Across the islet, intercellular communication between highly interconnected “hubs,” which act as pacemaker β-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 β-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.
AU  - Rutter,GA
AU  - Hodson,DJ
AU  - Chabosseau,P
AU  - Haythorne,E
AU  - Pullen,TJ
AU  - Leclerc,I
DO  - 10.1111/dom.12990
EP  - 41
PY  - 2017///
SN  - 1462-8902
SP  - 30
TI  - Local and regional control of calcium dynamics in the pancreatic islet
T2  - Diabetes, Obesity and Metabolism
UR  - http://dx.doi.org/10.1111/dom.12990
UR  - http://hdl.handle.net/10044/1/52009
VL  - 19
ER  -

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