| Autor: |
Kennedy, Robert T., Kauri, Lisa M., Dahlgren, Gabriella M., Sung-Kwon Jung |
| Předmět: |
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| Zdroj: |
Diabetes; Feb2002 Supplement, Vol. 51, pS152-S161, 10p |
| Abstrakt: |
Whereas the mechanisms underlying oscillatory insulin secretion remain unknown, several models have been advanced to explain if they involve generation of metabolic oscillations in β-cells. Evidence, including measurements of oxygen consumption, glucose consumption, NADH, and ATP/ADP ratio, has accumulated to support the hypothesis that energy metabolism in β-cells can oscillate. Where simultaneous measurements have been made, these oscillations are well correlated with oscillations in intracellular [Ca[sup 2+] and insulin secretion. Considerable evidence has been accumulated to suggest that entry of Ca[sup 2+] into cells can modulate metabolism both positively and negatively. The main positive effect of Ca[sup 2+] is an increase in oxygen consumption, believed to involve activation of mitochondrial dehydrogenases. Negative feedback by Ca[sup 2+] includes decreases in glucose consumption and decreases in the mitochondrial membrane potential. Ca[sup 2+] also provides negative feedback by increasing consumption of ATP. The negative feedback provided by Ca[sup 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[sup +](K[sub ATP]) channels, thus depolarizing the cell membrane and allowing Ca[sup 2+] entry through voltage-sensitive channels. Ca[sup 2+] entry reduces the ATP/ ADP ratio and allows reopening of the K[sub ATP] channel. Diabetes 51 (Suppl. 1):S152–S161, 2002 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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