BETA CELL OSCILLATORY RESPONSE IS NOT RESULT OF A SINGLE COMPONENT ACTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。脉冲胰岛素输出，与细胞内Ca2+的振荡平行，反映了细胞内对分泌燃料的振荡代谢。我们质疑振荡周期是保守的还是随着刺激的不同而变化，糖酵解对振荡反应的表现是否必要，以及营养过剩的环境是否影响振荡规律。我们已经确定，细胞振荡Ca2+模式独立于应用的分泌燃料类型（葡萄糖，丙酮酸甲酯（MeP）， a-酮异己酸（KIC））。因此，无论刺激燃料的类型如何，单个细胞在反复刺激时都以相同的模式做出反应。亚刺激（4mm）葡萄糖的存在并不是获得MeP或KIC振荡反应的必要条件。几个小时的葡萄糖剥夺（细胞在亚刺激浓度的MeP存在下培养）并不能阻止燃料刺激的振荡反应，也不能阻止胰岛素分泌。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pulsatile insulin output, paralleled by oscillations in intracellular Ca2+, reflects oscillating metabolism within ¿-cell in response to secretory fuels. We questioned whether oscillatory periodicity is conserved or varied from stimulation to stimulation, whether glycolysis is essential for the manifestation of the oscillatory response and whether the environment of nutrient oversupply affects oscillatory regularity. We have determined that a ¿-cell oscillatory Ca2+ pattern is independent of the type of applied secretory fuel (glucose, methyl-pyruvate (MeP), a-ketoisocaproate (KIC). Single cells thus respond with the same pattern when repeatedly stimulated, regardless of the type of stimulatory fuel. Presence of sub-stimulatory (4 mM) glucose was not necessary to obtain oscillatory response to MeP or KIC. Several hours of glucose deprivation (cells were cultured in the presence of sub-stimulatory concentration of MeP), did not prevent fuel-stimulated oscillatory response, nor insulin secretion.