Alterations of the Ca²⁺ signaling pathway in pancreatic beta-cells isolated from db/db mice
Protein & Cell
;
(12): 783-794, 2014.
Article
in English
| WPRIM
| ID: wpr-757650
ABSTRACT
Upon glucose elevation, pancreatic beta-cells secrete insulin in a Ca(2+)-dependent manner. In diabetic animal models, different aspects of the calcium signaling pathway in beta-cells are altered, but there is no consensus regarding their relative contributions to the development of beta-cell dysfunction. In this study, we compared the increase in cytosolic Ca(2+) ([Ca(2+)]i) via Ca(2+) influx, Ca(2+) mobilization from endoplasmic reticulum (ER) calcium stores, and the removal of Ca(2+) via multiple mechanisms in beta-cells from both diabetic db/db mice and non-diabetic C57BL/6J mice. We refined our previous quantitative model to describe the slow [Ca(2+)]i recovery after depolarization in beta-cells from db/db mice. According to the model, the activity levels of the two subtypes of the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump, SERCA2 and SERCA3, were severely down-regulated in diabetic cells to 65% and 0% of the levels in normal cells. This down-regulation may lead to a reduction in the Ca(2+) concentration in the ER, a compensatory up-regulation of the plasma membrane Na(+)/Ca(2+) exchanger (NCX) and a reduction in depolarization-evoked Ca(2+) influx. As a result, the patterns of glucose-stimulated calcium oscillations were significantly different in db/db diabetic beta-cells compared with normal cells. Overall, quantifying the changes in the calcium signaling pathway in db/db diabetic beta-cells will aid in the development of a disease model that could provide insight into the adaptive transformations of beta-cell function during diabetes development.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Potassium Chloride
/
Down-Regulation
/
Up-Regulation
/
Cell Membrane Permeability
/
Cells, Cultured
/
Calcium
/
Thapsigargin
/
Sodium-Calcium Exchanger
/
Calcium Signaling
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Protein & Cell
Year:
2014
Type:
Article
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