title: Metabolic oscillations in beta-cells.
abstract: Whereas the mechanisms underlying oscillatory insulin secretion remain unknown, several models have been advanced to explain if they involve generation of metabolic oscillations in beta-cells. Evidence, including measurements of oxygen consumption, glucose consumption, NADH, and ATP/ADP ratio, has accumulated to support the hypothesis that energy metabolism in beta-cells can oscillate. Where simultaneous measurements have been made, these oscillations are well correlated with oscillations in intracellular [Ca(2+)] and insulin secretion. Considerable evidence has been accumulated to suggest that entry of Ca(2+) into cells can modulate metabolism both positively and negatively. The main positive effect of Ca(2+) is an increase in oxygen consumption, believed to involve activation of mitochondrial dehydrogenases. Negative feedback by Ca(2+) includes decreases in glucose consumption and decreases in the mitochondrial membrane potential. Ca(2+) also provides negative feedback by increasing consumption of ATP. The negative feedback provided by Ca(2+) provides a mechanism for generating oscillations based on a model in which glucose stimulates a rise in ATP/ADP ratio that closes ATP-sensitive K(+) (K(ATP)) channels, thus depolarizing the cell membrane and allowing Ca(2+) entry through voltage-sensitive channels. Ca(2+) entry reduces the ATP/ADP ratio and allows reopening of the K(ATP) channel.
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL, USA. rtkenn@chem.ufl.edu
authors.forename: Robert T
authors.initials: RT
authors.lastname: Kennedy
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Kauri
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Dahlgren
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Jung
mesh_terms: D000818:Animals; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D010507:Periodicity
chemical_list: D007328:Insulin