Age-dependent changes in the exocytotic efficacy in Kir6.2 ablated mouse pancreatic β-cellsReportar como inadecuado




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In this study, we aimed to examine the electrophysio- logical properties of β-cells in Kir6.2- mice using fresh pancreatic tissue slice preparation. This prepa-ration is advantageous since it preserves socio-cellular context of the β-cells. Using this novel approach we revisited basic morphology and used whole-cell patch-clamp to study electrical excitability as well as to assess the modulation of the late steps of the exocy-totic activity of β-cells by cytosolic Ca2+ changes in control and Kir6.2- mice. We found that young Kir6.2- mice 2 - 4 weeks old were hypoglycaemic while aged Kir6.2- mice 5 - 60 weeks old were normo- or even hyper- glycaemic. Membrane ca-pacitance measurements show- ed more efficient Ca2+-secretion coupling in young Kir6.2- mice, but this coupling is significantly reduced in older Kir6.2- mice. We have found increased exo- cytotic efficacy induced by repetitive trains of depo- larization pulses which may result from higher cyto- solic Ca2+ due to hyperexcitability in Kir6.2- mice. This condition in turn resulted in the reduced β-cell number and func-tion in the following weeks. Detailed assessment of the efficacy of Ca2+ dependent exocyto- sis in β-cell from Kir6.2- mice may contribute to our understanding of the pathophysiology of persistent hyperinsulinemia hypoglycemia of infancy PHHI and suggest potential alternative therapeutic approaches for PHHI patients.

KEYWORDS

Islets of Langerhans; Insulin; Hyperinsulinism; Persistent Hyperinsulinemia Hypoglycemia of Infancy; Ion Channels; Patch-Clamp Techniques

Cite this paper

Beaudelaire Tsiaze, E. , Huang, Y. , Bombek, L. , Yang, S. , Jevšek, M. , Seino, S. and Slak Rupnik, M. 2012 Age-dependent changes in the exocytotic efficacy in Kir6.2 ablated mouse pancreatic β-cells. Open Journal of Molecular and Integrative Physiology, 2, 51-60. doi: 10.4236-ojmip.2012.23008.





Autor: Ernest Beaudelaire Tsiaze, Ya-Chi Huang, Lidija Križančić Bombek, Shi-Bing Yang, Marko Jevšek, Susumu Seino, Marjan Slak Rupn

Fuente: http://www.scirp.org/



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