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Ghrelin Attenuates ...
Ghrelin Attenuates cAMP-PKA Signaling to Evoke Insulinostatic Cascade in Islet beta-Cells
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Dezaki, Katsuya (författare)
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Damdindorj, Boldbaatar (författare)
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Sone, Hideyuki (författare)
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- Dyachok, Oleg, 1965- (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Gylfe Tengholm
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- Tengholm, Anders, 1971- (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Gylfe, Erik, 1947- (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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Kurashina, Tomoyuki (författare)
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Yoshida, Masashi (författare)
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Kakei, Masafumi (författare)
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Yada, Toshihiko (författare)
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(creator_code:org_t)
- 2011-08-20
- 2011
- Engelska.
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 60:9, s. 2315-2324
- Relaterad länk:
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http://diabetes.diab...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- OBJECTIVE-Ghrelin reportedly restricts insulin release in islet beta-cells via the G alpha(i2) subtype of G-proteins and thereby regulates glucose homeostasis. This study explored whether ghrelin regulates cAMP signaling and whether this regulation induces insulinostatic cascade in islet beta-cells. RESEARCH DESIGN AND METHODS-Insulin release was measured in rat perfused pancreas and isolated islets and cAMP production in isolated islets. Cytosolic cAMP concentrations ([cAMP](i)) were monitored in mouse MIN6 cells using evanescent-wave fluorescence imaging. In rat single beta-cells, cytosolic protein kinase-A activity ([PKA](i)) and Ca(2+) concentration ([Ca(2+)](i)) were measured by DR-II and fura-2 microfluorometry, respectively, and whole cell currents by patch-clamp technique. RESULTS-Ghrelin suppressed glucose (8.3 mmol/L)-induced insulin release in rat perfused pancreas and isolated islets, and these effects of ghrelin were blunted in the presence of cAMP analogs or adenylate cyclase inhibitor. Glucose-induced cAMP production in isolated islets was attenuated by ghrelin and enhanced by ghrelin receptor antagonist and anti-ghrelin antiserum, which counteract endogenous islet-derived ghrelin. Ghrelin inhibited the glucose-induced [cAMP](i) elevation and [PKA](i) activation in MIN6 and rat beta-cells, respectively. Furthermore, ghrelin potentiated voltage-dependent K(+) (Kv) channel currents without altering Ca(2+) channel currents and attenuated glucose-induced [Ca(2+)](i) increases in rat beta-cells in a PKA-dependent manner. CONCLUSIONS-Ghrelin directly interacts with islet beta-cells to attenuate glucose-induced cAMP production and PKA activation, which lead In activation of Kv channels and suppression of glucose-induced [Ca(2+)](i) increase and insulin release.
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Diabetes
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Dezaki, Katsuya
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Damdindorj, Bold ...
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Sone, Hideyuki
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Dyachok, Oleg, 1 ...
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Tengholm, Anders ...
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Gylfe, Erik, 194 ...
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Kurashina, Tomoy ...
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Yoshida, Masashi
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Kakei, Masafumi
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Yada, Toshihiko
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Diabetes
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Uppsala universitet