Author(s)

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

Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
European Neuroscience Institute, G?ttingen, Germany.
Howard Hughes Medical Institute, San Francisco, USA.
Institute of Medical Science, University of Toronto, Toronto, Canada.
Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia.

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.

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

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.