Search: onr:"swepub:oai:DiVA.org:uu-159241" >
Ghrelin Attenuates ...
Ghrelin Attenuates cAMP-PKA Signaling to Evoke Insulinostatic Cascade in Islet beta-Cells
-
Dezaki, Katsuya (author)
-
Damdindorj, Boldbaatar (author)
-
Sone, Hideyuki (author)
-
show more...
-
- Dyachok, Oleg, 1965- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Gylfe Tengholm
-
- Tengholm, Anders, 1971- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
-
- Gylfe, Erik, 1947- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
-
Kurashina, Tomoyuki (author)
-
Yoshida, Masashi (author)
-
Kakei, Masafumi (author)
-
Yada, Toshihiko (author)
-
show less...
-
(creator_code:org_t)
- 2011-08-20
- 2011
- English.
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 60:9, s. 2315-2324
- Related links:
-
http://diabetes.diab...
-
show more...
-
https://urn.kb.se/re...
-
https://doi.org/10.2...
-
show less...
Abstract
Subject headings
Close
- 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.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
-
Diabetes
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
-
Dezaki, Katsuya
-
Damdindorj, Bold ...
-
Sone, Hideyuki
-
Dyachok, Oleg, 1 ...
-
Tengholm, Anders ...
-
Gylfe, Erik, 194 ...
-
show more...
-
Kurashina, Tomoy ...
-
Yoshida, Masashi
-
Kakei, Masafumi
-
Yada, Toshihiko
-
show less...
- Articles in the publication
-
Diabetes
- By the university
-
Uppsala University