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© 2002 by the American Diabetes Association, Inc.
Section 4: Oscillations in ß-Cells |
Metabolic Oscillations in ß-Cells
Department of Chemistry, University of Florida, Gainesville, Florida, Woods Hole, Massachusetts
BioCurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts
Whereas the mechanisms underlying oscillatory insulin secretion remain unknown, several models have been advanced to explain if they involve generation of metabolic oscillations in ß-cells. Evidence, including measurements of oxygen consumption, glucose consumption, NADH, and ATP/ADP ratio, has accumulated to support the hypothesis that energy metabolism in ß-cells can oscillate. Where simultaneous measurements have been made, these oscillations are well correlated with oscillations in intracellular [Ca2+] and insulin secretion. Considerable evidence has been accumulated to suggest that entry of Ca2+ into cells can modulate metabolism both positively and negatively. The main positive effect of Ca2+ is an increase in oxygen consumption, believed to involve activation of mitochondrial dehydrogenases. Negative feedback by Ca2+ includes decreases in glucose consumption and decreases in the mitochondrial membrane potential. Ca2+ also provides negative feedback by increasing consumption of ATP. The negative feedback provided by Ca2+ 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+ (KATP) channels, thus depolarizing the cell membrane and allowing Ca2+ entry through voltage-sensitive channels. Ca2+ entry reduces the ATP/ADP ratio and allows reopening of the KATP channel.
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