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Calcium signaling in a genetically engineered human pancreatic β-cell line
KTH, School of Engineering Sciences (SCI), Applied Physics.ORCID iD: 0000-0002-5970-2985
Karolinska Institutet.
Karolinska institutet.
Karolinska institutet.
2015 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 44, no 5, 773-777 p.Article in journal, Editorial material (Refereed) Published
Abstract [en]

Objectives: The use of primary human β-cells for studying Ca2+ signalingis limited by the scarcity of human pancreatic islets. Rodent insulinomacell lines are widely used, but it is difficult to extrapolate results obtainedfrom rodent cells to human. Recently, a genetically engineered humanβ-cell line EndoC-BH1 has been developed. We have examined whetherthe EndoC-BH1 cells could be used as a model for studying Ca2+ signalingin the β-cells.Methods: We used microscope-based fluorometry to measure cytoplasmicfreeCa2+ concentration from fura-2–loaded single EndoC-BH1 cellscultured on glass cover slips. Ca2+ responses to different agonists of insulinsecretion were studied. Insulin secretion was measured by radioimmunoassay.Results: EndoC-BH1 cells secreted insulin in response to glucose ina dose-dependent manner, and the secretion was enhanced by GLP-1(glucagon-like peptide 1). Glucose, potassium chloride, carbachol, L-arginine,and tolbutamide increased cytoplasmic-free Ca2+ concentration in theEndoC-BH1 cells. We found that GLP-1 was essential for Ca2+ responseto glucose and tolbutamide.Conclusions: We concluded that the EndoC-BH1 cells can be used asmodel cells to study Ca2+ signaling and stimulus-secretion coupling inthe human β-cells.

Place, publisher, year, edition, pages
2015. Vol. 44, no 5, 773-777 p.
Keyword [en]
calcium signaling, human β-cell line, insulin, stimulus-secretion coupling, EndoC-BH1 cells
National Category
Medical and Health Sciences
Research subject
Medical Technology
Identifiers
URN: urn:nbn:se:kth:diva-204561OAI: oai:DiVA.org:kth-204561DiVA: diva2:1085186
Note

QC 20170328

Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2017-03-28Bibliographically approved
In thesis
1. Studies on molecular mechanisms in calcium signaling and cellular energy consumption
Open this publication in new window or tab >>Studies on molecular mechanisms in calcium signaling and cellular energy consumption
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ion signaling plays fundamental role in cell survival. Na+ and Ca2+ are critical players in ion signaling. Cells spend the major amount of energy to maintain and regulate Na+ and Ca2+ gradients across the cell membrane. Any disruption in cellular energy consumption by plasma membrane ATPases affects ion signaling and vice versa. This thesis is a combination of four separate research studies. In the first study, We measured ATP consumption dynamics of Na+/K+-ATPase using a genetically encoded fluorescent indicator called Perceval HR. we demonstrate that PercevalHR is an excellent tool to visualize ATP:ADP in mammalian cells.

In the second study, We studied the role of calcium signaling and TRP channels in angiotensin II type 1 receptor  signaling cascade. We prove that low inhibition of CaV1.2 with physiological and therapeutically relevant concentration of Angiotensin II up regulate AT1R signaling.

In the third study, We studied the role of the TRPM5 channel in regulating insulin secretion, and cytoplasmic free calcium concentration in the rat β-cells by usingtriphenyl phosphine oxide, a selective inhibitor of the channel.

In the fourth study, We tested whether, the genetically engineered human β-cell line (EndoC-BH1) could be used as models for studying Ca2+signaling in the context of Type II Diabetes. We found that the EndoC-BH1 cells could be a relevant model to study stimulus-secretion coupling and Ca2+ signaling in the human β-cells.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2017. 76 p.
Keyword
ca2+ signaling, ATP, PercevalHR, NKA, diabetes, Angiotensin
National Category
Medical and Health Sciences
Research subject
Biological Physics
Identifiers
urn:nbn:se:kth:diva-204418 (URN)978-91-7729-337-8 (ISBN)
Public defence
2017-04-19, Fire, Scilifelab, Tomtebodavägen 23a, Solna, 09:00 (English)
Opponent
Supervisors
Note

QC 20170328

Available from: 2017-03-28 Created: 2017-03-27 Last updated: 2017-03-28Bibliographically approved

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