| Author/Editor | Tsiaze, Ernest Beaudelaire; Huang, Ya-Chi; Križančić Bombek, Lidija; Yang, Shi-Bing; Jevšek, Marko; Seino, Susumu; Rupnik, Marjan | |
| Title | Age-dependent changes in the exocytotic efficacy in Kir6.2 ablated mouse pancreatic ß-cells | |
| Type | članek | |
| Vol. and No. | Letnik 2, št. 3 | |
| Publication year | 2012 | |
| Volume | str. 51-60 | |
| ISSN | 2162-2159 - Open Journal of Molecular and Integrative Physiology | |
| Language | eng | |
| Abstract | In this study, we aimed to examine the electrophysiological properties of ß-cells in Kir6.2-/- mice using fresh pancreatic tissue slice preparation. This preparation is advantageous since it preserves sociocellular context of the ß-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 ß-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 capacitance measurements showed 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 exocytotic efficacy induced by repetitive trains of depolarization pulses which may result from higher cytosolic [Ca2+] due to hyperexcitability in Kir6.2-/- mice. This condition in turn resulted in the reduced ß-cell number and function in the following weeks. Detailed assessment of the efficacy of Ca2+ dependent exocytosis in ß-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. | |
| Descriptors | Islets of Langerhans Langerhansovi otočki Hyperinsulinism Hiperinzulinizem Persistent Hyperinsulinemia Hypoglycemia of Infancy Perzistentna hiperinzulinemija in hipoglikemija, v detinstvu Ion Channels Ionski kanalčki Patch-Clamp Techniques Snov-vnos, tehnike Models, Animal Živalski modeli |