Glucose-dependent increase in mitochondrial membrane potential, but not cytoplasmic calcium, correlates with insulin secretion in single islet cells.

We examined the effects of different physiological concentrations of glucose on cytoplasmic Ca(2+) handling and mitochondrial membrane potential (Deltapsi(m)) and insulin secretion in single mouse islet cells. The threshold for both glucose-induced changes in Ca(2+) and Deltapsi(m) ranged from 6 to 8 mM. Glucose step-jumps resulted in sinusoidal oscillations of cytoplasmic Ca(2+), whereas Deltapsi(m) reached sustained plateaus with oscillations interposed on the top of these plateaus. The amplitude of the Ca(2+) rise (height of the peak) did not vary with glucose concentration, suggesting a "digital" rather than "analog" character of this aspect of the oscillatory Ca(2+) response. The average glucose-dependent elevation of cytoplasmic Ca(2+) concentration during glucose stimulation reached saturation at 8 mM stimulatory glucose, whereas Deltapsi(m) showed a linear glucose dose-response relationship over the range of stimulatory glucose concentrations (4-16 mM). Glucose-dependent increases in insulin secretion correlated well with Deltapsi(m), but not with average Ca(2+) concentration. These data show that an ATP-dependent K(+) channel-independent pathway is operative at the single cell level and suggest mitochondrial metabolism may be a determining factor in explaining graded, glucose concentration-dependent increases in insulin secretion.