Leptin is produced and secreted from islets of Langerhans, but the secretory dynamics and functions of leptin in this setting are unknown. The long-term goal is to quantitatively and simultaneously monitor secretion of peptides and proteins involved in the communication pathway between adipocytes and islets of Langerhans. The overall objective of this application is the development of technology to measure acute changes in leptin secretion from islets of Langerhans and determine how this secretion affects the release of traditional peptides. The central hypothesis is that islet-secreted leptin affects systemic glucose homeostasis by altering islet physiology. To test this hypothesis, the following aims will be accomplished: 1.) acute secretory dynamics of islet-secreted leptin will be determined using an immuno-PCR assay on a microfluidic device, 2.) the effect of leptin on islet physiology will be ascertained by simultaneously monitoring insulin, glucagon, and amylin secretion from islets of Langerhans on a microfluidic device using a multi-color electrophoretic immunoassay, and 3.) the effects that culture conditions have on islet-secreted leptin will be determined using a combination of the technology developed in aims 1 and 2. This work is significant as the role of islet-secreted leptin has not been defined and may identify a new mechanism that influences blood glucose levels. The methodology developed will also be applicable to other biological systems for measurement of simultaneous peptide or protein secretion. The function of islet-secreted leptin has not been investigated, but has the potential to impact broad areas of human health. The proposed research has relevance to public health because this knowledge will increase our understanding of islet biology and potentially provide new routes for alleviating complications associated with diabetes and obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK080714-05
Application #
8235058
Study Section
Enabling Bioanalytical and Biophysical Technologies Study Section (EBT)
Program Officer
Appel, Michael C
Project Start
2008-04-01
Project End
2013-03-31
Budget Start
2012-03-01
Budget End
2013-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$277,478
Indirect Cost
$81,458
Name
Florida State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
790877419
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
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Yi, Lian; Bandak, Basel; Wang, Xue et al. (2016) Dual Detection System for Simultaneous Measurement of Intracellular Fluorescent Markers and Cellular Secretion. Anal Chem 88:10368-10373
Schrell, Adrian M; Mukhitov, Nikita; Roper, Michael G (2016) Multiplexing Fluorescence Anisotropy Using Frequency Encoding. Anal Chem 88:7910-5
Wang, Xue; Yi, Lian; Guillo, Christelle et al. (2015) Micellar electrokinetic chromatography method for measuring amino acid secretions from islets of Langerhans. Electrophoresis 36:1172-8
Yi, Lian; Wang, Xue; Dhumpa, Raghuram et al. (2015) Integrated perfusion and separation systems for entrainment of insulin secretion from islets of Langerhans. Lab Chip 15:823-32
Dhumpa, Raghuram; Truong, Tuan M; Wang, Xue et al. (2015) Measurement of the entrainment window of islets of Langerhans by microfluidic delivery of a chirped glucose waveform. Integr Biol (Camb) 7:1061-7
Wang, Xue; Yi, Lian; Mukhitov, Nikita et al. (2015) Microfluidics-to-mass spectrometry: a review of coupling methods and applications. J Chromatogr A 1382:98-116
Wang, Xue; Roper, Michael G (2014) Measurement of DCF fluorescence as a measure of reactive oxygen species in murine islets of Langerhans. Anal Methods 6:3019-3024
Mukhitov, Nikita; Yi, Lian; Schrell, Adrian M et al. (2014) Optimization of a microfluidic electrophoretic immunoassay using a Peltier cooler. J Chromatogr A 1367:154-60
Schrell, Adrian M; Roper, Michael G (2014) Frequency-encoded laser-induced fluorescence for multiplexed detection in infrared-mediated quantitative PCR. Analyst 139:2695-701

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