Role of hexose monophosphate shunt in parathyroid hormone secretion

The metabolism of labeled glucose by collagenase-dispersed bovine parathyroid cells was examined. When the medium calcium ion concentration was increased to 2.0 mM, the rate of ¹⁴CO₂ release from [1-¹⁴C]glucose was increased 169 ± 45% compared with the rate at 0.5 mM calcium. There was no significant change in the rate of ¹4CO₂ release from [6-¹⁴C]glucose by this maneuver. The greatest increase in ¹⁴CO₂ release and decrease in parathyroid hormone secretion occurred between medium calcium ion concentrations of 0.5-1.5 mM. This difference in the metabolism of glucose represents a true increase in hexose shunt activity because the incorporation of label from either [1-¹⁴C]- or [6-¹⁴C]glucose into parathyroid tissue lipids was equal. This suggests equilibration of label at the level of triosephosphates. The increase in hexose shunt activity was not due to a calcium-mediated increase in glucose uptake because calcium changes did not affect 2-[³H]deoxyglucose transport by the cells. Phenazine methosulfate added to cells incubated at 0.5 mM calcium selectively increased hexose shunt activity in a dose-dependent manner (91 ± 33% overall) and concomitantly inhibited parathyroid hormone secretion 65% overall at 0.5 mM calcium. The compound 6-aminonicotinamide inhibited hexose shunt activity but could not overcome the inhibition of hormone secretion at 2.0 mM calcium. A decrease in protein biosynthesis cannot fully explain the inhibition of hormone secretion by calcium or phenazine methosulfate because [³H]leucine incorporation into total cell protein was not as affected as secretion. These results suggest that an increase in hexose shunt activity of dispersed bovine parathyroid cells is in some manner linked to an inhibition of hormone secretion.