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Endocrine system on chip for a diabetes treatment model
Ewha Womans Univ, Dept Chem & Nano Sci, Seoul 03760, South Korea.
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
Kyung Hee University, South Korea.
Sungkyunkwan University, South Korea.
2017 (English)In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 9, no 1, article id 015021Article in journal (Refereed) Published
Abstract [en]

The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an endocrine system on chip to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting beta-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion. Thus, we constructed a co-culture of intestinal-pancreatic cells to measure the effect of glucose on the production of glucagon-like peptide-1 (GLP-1) from the L-cell line (GLUTag) and insulin from the pancreatic beta-cell line (INS-1). After three days of culture, both cell lines formed aggregates, exhibited 3D cell morphology, and showed good viability (amp;gt; 95%). We separately measured the dynamic profile of GLP-1 and insulin release at glucose concentrations of 0.5 and 20 mM, as well as the combined effect of GLP-1 on insulin production at these glucose concentrations. In response to glucose stimuli, GLUTag and INS-1 cells produced higher amounts of GLP-1 and insulin, respectively, compared to a static 2D cell culture. INS-1 combined with GLUTag cells exhibited an even higher insulin production in response to glucose stimulation. At higher glucose concentrations, the diabetes model on chip showed faster saturation of the insulin level. Our results suggest that the endocrine system developed in this study is a useful tool for observing dynamical changes in endocrine hormones (GLP-1 and insulin) in a glucose-dependent environment. Moreover, it can potentially be used to screen GLP-1 analogues and natural insulin and GLP-1 stimulants for diabetes treatment.

Place, publisher, year, edition, pages
IOP PUBLISHING LTD , 2017. Vol. 9, no 1, article id 015021
Keywords [en]
endocrine system; insulin; GLP-1; multi-organ on a chip; microfluidic cell culture device
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-136651DOI: 10.1088/1758-5090/aa5cc9ISI: 000395861900001PubMedID: 28222044OAI: oai:DiVA.org:liu-136651DiVA, id: diva2:1089833
Note

Funding Agencies|Technology Innovation Program - Ministry of Trade, Industry Energy (MI) [10050154]; National Research Foundation (NRF) - Ministry of Science, ICT and Future Planning (MSIP) in Korea [2016M3A9B4917320]

Available from: 2017-04-21 Created: 2017-04-21 Last updated: 2018-01-13

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