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

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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.