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

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 Δψmranged from 6 to 8 mM. Glucose step-jumps resulted in sinusoidal oscillations of cytoplasmic Ca2+, whereas Δψmreached 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 Δψmshowed 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.