title: 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 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.
authors.affiliation: Department of Medicine, Obesity Research Center, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Heart
authors.forename: Richard F
authors.initials: RF
authors.lastname: Corkey
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Wikstrom
authors.forename: Orian S
authors.initials: OS
authors.lastname: Shirihai
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Corkey
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007328:Insulin; D005947:Glucose; D002118:Calcium