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

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Abstract
We examined the effects of different physiological concentrations of glucose on cytoplasmic Ca2+ handling and mitochondrial membrane potential (Δψm) and insulin secretion in single mouse islet cells. The threshold for both glucose-induced changes in Ca2+ and Δψm ranged from 6 to 8 mM. Glucose step-jumps resulted in sinusoidal oscillations of cytoplasmic Ca2+, whereas Δψm reached sustained plateaus with oscillations interposed on the top of these plateaus. The amplitude of the Ca2+ rise (height of the peak) did not vary with glucose concentration, suggesting a “digital” rather than “analog” character of this aspect of the oscillatory Ca2+ response. The average glucose-dependent elevation of cytoplasmic Ca2+ concentration during glucose stimulation reached saturation at 8 mM stimulatory glucose, whereas Δψm 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 Δψm, but not with average Ca2+ 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.