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| Content Provider | Springer Nature Link |
|---|---|
| Author | Drews, Gisela Bauer, Cita Edalat, Armin Düfer, Martina Krippeit Drews, Peter |
| Copyright Year | 2015 |
| Abstract | Pancreatic beta-cells respond to an unchanging stimulatory glucose concentration with oscillations in membrane potential (Vm), cytosolic Ca2+ concentration ([Ca2+]c), and insulin secretion. The underlying mechanisms are largely ascertained. Some particular details, however, are still in debate. Stimulus-secretion coupling (SSC) of beta-cells comprises glucose-induced Ca2+ influx into the cytosol and thus into mitochondria. It is suggested that this activates (mitochondrial) dehydrogenases leading to an increase in reduction equivalents and ATP production. According to SSC, a glucose-induced increase in ATP production would thus further augment ATP production, i.e. induce a feed-forward loop that is hardly compatible with oscillations. Consistently, other studies favour a feedback mechanism that drives oscillatory mitochondrial ATP production. If Ca2+ influx activates dehydrogenases, a change in [Ca2+]c should increase the concentration of reduction equivalents. We measured changes in flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) autofluorescence in response to changes in glucose concentration or glucose-independent changes in [Ca2+]c. The FAD signal was altered by glucose but not by alterations in [Ca2+]c. NAD(P)H was increased by glucose but even decreased by Ca2+ influx evoked by tolbutamide. The mitochondrial membrane potential ΔΨ was hyperpolarized by 4 mM glucose. As adding tolbutamide then depolarized ΔΨ, we deduce that Ca2+ does not activate mitochondrial activity but by contrast even inhibits it by reducing the driving force for ATP production. Inhibition of Ca2+ influx reversed the Ca2+-induced changes in ΔΨ and NAD(P)H. The results are consistent with a feedback mechanism which transiently and repeatedly reduces ATP production and explain the oscillatory activity of pancreatic beta-cells at increased glucose concentrations. |
| Starting Page | 2389 |
| Ending Page | 2397 |
| Page Count | 9 |
| File Format | |
| ISSN | 00316768 |
| Journal | Pflügers Archiv |
| Volume Number | 467 |
| Issue Number | 11 |
| e-ISSN | 14322013 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2015-04-18 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Beta-cell Flavin adenine dinucleotide (FAD) Nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) Mitochondrial membrane potential Dehydrogenase Calcium Oscillations Human Physiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) Clinical Biochemistry |
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