Abstract
Closure of ATP-sensitive K+ (KATP) channels is part of the stimulus-secretion coupling mechanism in the pancreatic β-cell, leading to membrane depolarization and influx of Ca2+ through voltage-sensitive L-type Ca2+ channels. The elevated ATP/ADP ratio seen in the presence of high levels of glucose has been postulated to mediate the glucose-induced closure of the KATP channels and rise in cytoplasmic free Ca2+ concentration ([Ca2+]i), or alternatively to be a consequence of activation of mitochondrial dehydrogenases by the increase in [Ca2+]i. To distinguish between these two possibilities, the time course of the change in the ATP/ADP ratio was determined in comparison with that of [Ca2+]i. We here show that a severalfold rise in the ATP/ADP ratio occurs rapidly on stimulation of suspensions of mouse pancreatic β-cells with glucose. The change in the ATP/ ADP ratio is an early event that begins within 20-40 s and precedes the rise in [Ca2+]i. The temporal relationship indicates that the adenine nucleotide changes cannot be a consequence of the [Ca2+]i changes and may indeed be the connecting link between glucose metabolism and [Ca2+]i changes. When the cells were sequentially treated with high glucose concentration, clonidine and finally high extracellular Ca2+ concentration to induce synchronized oscillations in [Ca2+]i in the cell suspension, corresponding oscillations in the ATP/ADP ratio were observed. Glucose 6-phosphate levels oscillated out of phase with the ATP/ADP ratio. These results support the hypothesis that the Ca2+ oscillations previously observed in glucose-stimulated single islets or β-cells may reflect oscillations in the ATP/ADP ratio that accompany oscillatory glycolysis.
| Original language | English |
|---|---|
| Pages (from-to) | 91-94 |
| Number of pages | 4 |
| Journal | Biochemical Journal |
| Volume | 314 |
| Issue number | 1 |
| State | Published - Feb 15 1996 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic β-cells. / Nilsson, Thomas; Schultz, Vera; Berggren, Per Olof; Corkey, Barbara E.; Tornheim, Keith.
In: Biochemical Journal, Vol. 314, No. 1, 15.02.1996, p. 91-94.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic β-cells
AU - Nilsson, Thomas
AU - Schultz, Vera
AU - Berggren, Per Olof
AU - Corkey, Barbara E.
AU - Tornheim, Keith
PY - 1996/2/15
Y1 - 1996/2/15
N2 - Closure of ATP-sensitive K+ (KATP) channels is part of the stimulus-secretion coupling mechanism in the pancreatic β-cell, leading to membrane depolarization and influx of Ca2+ through voltage-sensitive L-type Ca2+ channels. The elevated ATP/ADP ratio seen in the presence of high levels of glucose has been postulated to mediate the glucose-induced closure of the KATP channels and rise in cytoplasmic free Ca2+ concentration ([Ca2+]i), or alternatively to be a consequence of activation of mitochondrial dehydrogenases by the increase in [Ca2+]i. To distinguish between these two possibilities, the time course of the change in the ATP/ADP ratio was determined in comparison with that of [Ca2+]i. We here show that a severalfold rise in the ATP/ADP ratio occurs rapidly on stimulation of suspensions of mouse pancreatic β-cells with glucose. The change in the ATP/ ADP ratio is an early event that begins within 20-40 s and precedes the rise in [Ca2+]i. The temporal relationship indicates that the adenine nucleotide changes cannot be a consequence of the [Ca2+]i changes and may indeed be the connecting link between glucose metabolism and [Ca2+]i changes. When the cells were sequentially treated with high glucose concentration, clonidine and finally high extracellular Ca2+ concentration to induce synchronized oscillations in [Ca2+]i in the cell suspension, corresponding oscillations in the ATP/ADP ratio were observed. Glucose 6-phosphate levels oscillated out of phase with the ATP/ADP ratio. These results support the hypothesis that the Ca2+ oscillations previously observed in glucose-stimulated single islets or β-cells may reflect oscillations in the ATP/ADP ratio that accompany oscillatory glycolysis.
AB - Closure of ATP-sensitive K+ (KATP) channels is part of the stimulus-secretion coupling mechanism in the pancreatic β-cell, leading to membrane depolarization and influx of Ca2+ through voltage-sensitive L-type Ca2+ channels. The elevated ATP/ADP ratio seen in the presence of high levels of glucose has been postulated to mediate the glucose-induced closure of the KATP channels and rise in cytoplasmic free Ca2+ concentration ([Ca2+]i), or alternatively to be a consequence of activation of mitochondrial dehydrogenases by the increase in [Ca2+]i. To distinguish between these two possibilities, the time course of the change in the ATP/ADP ratio was determined in comparison with that of [Ca2+]i. We here show that a severalfold rise in the ATP/ADP ratio occurs rapidly on stimulation of suspensions of mouse pancreatic β-cells with glucose. The change in the ATP/ ADP ratio is an early event that begins within 20-40 s and precedes the rise in [Ca2+]i. The temporal relationship indicates that the adenine nucleotide changes cannot be a consequence of the [Ca2+]i changes and may indeed be the connecting link between glucose metabolism and [Ca2+]i changes. When the cells were sequentially treated with high glucose concentration, clonidine and finally high extracellular Ca2+ concentration to induce synchronized oscillations in [Ca2+]i in the cell suspension, corresponding oscillations in the ATP/ADP ratio were observed. Glucose 6-phosphate levels oscillated out of phase with the ATP/ADP ratio. These results support the hypothesis that the Ca2+ oscillations previously observed in glucose-stimulated single islets or β-cells may reflect oscillations in the ATP/ADP ratio that accompany oscillatory glycolysis.
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UR - http://www.scopus.com/inward/citedby.url?scp=0030043256&partnerID=8YFLogxK
M3 - Article
C2 - 8660314
AN - SCOPUS:0030043256
VL - 314
SP - 91
EP - 94
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 1
ER -