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Glucose stimulates ...
Glucose stimulates somatostatin secretion in pancreatic delta-cells by cAMP-dependent intracellular Ca-2+ release
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Denwood, G. (författare)
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Tarasov, A. (författare)
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- Salehi, Albert (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Vergari, L. (författare)
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Ramracheya, R. (författare)
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Takahashi, H. (författare)
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Nikolaev, V. O. (författare)
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Seino, S. (författare)
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Gribble, F. (författare)
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Reimann, F. (författare)
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- Rorsman, Patrik, 1959 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Zhang, Q. (författare)
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(creator_code:org_t)
- 2019-07-29
- 2019
- Engelska.
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Ingår i: Journal of General Physiology. - : Rockefeller University Press. - 0022-1295 .- 1540-7748. ; 151:9, s. 1094-1115
- Relaterad länk:
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https://rupress.org/...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Somatostatin secretion from pancreatic islet delta-cells is stimulated by elevated glucose levels, but the underlying mechanisms have only partially been elucidated. Here we show that glucose-induced somatostatin secretion (GISS) involves both membrane potential-dependent and -independent pathways. Although glucose-induced electrical activity triggers somatostatin release, the sugar also stimulates GISS via a cAMP-dependent stimulation of CICR and exocytosis of somatostatin. The latter effect is more quantitatively important and in mouse islets depolarized by 70 mM extracellular K+, increasing glucose from 1 mM to 20 mM produced an similar to 3.5-fold stimulation of somatostatin secretion, an effect that was mimicked by the application of the adenylyl cyclase activator forskolin. Inhibiting cAMP-dependent pathways with PKI or ESI-05, which inhibit PKA and exchange protein directly activated by cAMP 2 (Epac2), respectively, reduced glucose/forskolin-induced somatostatin secretion. Ryanodine produced a similar effect that was not additive to that of the PKA or Epac2 inhibitors. Intracellular application of cAMP produced a concentration-dependent stimulation of somatostatin exocytosis and elevation of cytoplasmic Ca2+ ([Ca2+](i)). Both effects were inhibited by ESI-05 and thapsigargin (an inhibitor of SERCA). By contrast, inhibition of PKA suppressed delta-cell exocytosis without affecting [Ca2+](i) . Simultaneous recordings of electrical activity and [Ca2+](i) in delta-cells expressing the genetically encoded Ca2+ indicator GCaMP3 revealed that the majority of glucose-induced [Ca2+](i) spikes did not correlate with delta-cell electrical activity but instead reflected Cat' release from the ER. These spontaneous [Ca2+](i) spikes are resistant to PKI but sensitive to ESI-05 or thapsigargin. We propose that cAMP links an increase in plasma glucose to stimulation of somatostatin secretion by promoting CICR, thus evoking exocytosis of somatostatin-containing secretory vesicles in the delta-cell.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- insulin granule dynamics
- beta-cells
- cyclic-amp
- glucagon-secretion
- cytoplasmic calcium
- electrical-activity
- ca2+ release
- mouse islets
- alpha-cells
- c-epsilon
- Physiology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Denwood, G.
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Tarasov, A.
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Salehi, Albert
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Vergari, L.
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Ramracheya, R.
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Takahashi, H.
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visa fler...
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Nikolaev, V. O.
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Seino, S.
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Gribble, F.
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Reimann, F.
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Rorsman, Patrik, ...
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Zhang, Q.
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visa färre...
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Göteborgs universitet