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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Enabling Bioanalytical and Biophysical Technologies Study Section (EBT)
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Appel, Michael C
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Florida State University
Schools of Arts and Sciences
United States
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Schrell, Adrian M; Mukhitov, Nikita; Yi, Lian et al. (2017) Online fluorescence anisotropy immunoassay for monitoring insulin secretion from islets of Langerhans. Anal Methods 9:38-45
Schrell, Adrian M; Mukhitov, Nikita; Roper, Michael G (2016) Multiplexing Fluorescence Anisotropy Using Frequency Encoding. Anal Chem 88:7910-5
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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
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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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