Thiazolidinediones (PPARγ agonists) but not PPAR α agonists increase IRS‐2 gene expression in 3T3‐L1 and human adipocytes1

Abstract

Although the role of calcium (Ca²⁺) in the signal transduction and pathobiology of the exocrine pancreas is firmly established, the role of magnesium (Mg²⁺) remains unclear. We have characterized the intracellular distribution of Mg²⁺ in response to hormone stimulation in isolated mouse pancreatic acinar cells and studied the role of Mg²⁺ in modulating Ca²⁺ signaling using microspectrofluorometry and digital imaging of Ca²⁺- or Mg²⁺-sensitive fluorescent dyes as well as Mg²⁺-sensitive intracellular microelectrodes. Our results indicate that an increase in intracellular Mg²⁺ concentrations reduced the cholecystokinin (CCK) -induced Ca²⁺ oscillations by inhibiting the capacitive Ca²⁺ influx. An intracellular Ca²⁺ mobilization, on the other hand, was paralleled by a decrease in [Mg²⁺]_i, which was reversible upon hormone withdrawal independent of the electrochemical gradients for Mg²⁺, Ca²⁺, Na⁺, and K⁺, and not caused by Mg²⁺ efflux from acinar cells. In an attempt to characterize possible Mg²⁺ stores that would explain the reversible, hormone-induced intracellular Mg²⁺ movements, we ruled out mitochondria or ATP as potential Mg²⁺ buffers and found that the CCK-induced [Mg²⁺]_i decrease was initiated at the basolateral part of the acinar cells, where most of the endoplasmic reticulum (ER) is located, and progressed from there toward the apical pole of the acinar cells in an antiparallel fashion to Ca²⁺ waves. These experiments represent the first characterization of intracellular Mg²⁺ movements in the exocrine pancreas, provide evidence for possible Mg²⁺ stores in the ER, and indicate that the spatial and temporal distribution of intracellular Mg concentrations profoundly affects acinar cell Ca²⁺ signaling.—Mooren, F. C., Turi, S., Günzel, D., Schlue, W.-R., Domschke, W., Singh, J., Lerch, M. M. Calcium–magnesium interactions in pancreatic acinar cells.