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Microfluidic Devices For Determining Dynamics Of Islets of Langerhans

Award Number: R01DK080714
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2008
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Microfluidic Devices For Determining Dynamics Of Islets of Langerhans - The mechanisms that synchronize hormone secretion across millions of islets of Langerhans in the pancreas are unknown. The long-term goal of the Roper laboratory is to decode cellular communication to enable understanding of normal biological function and disease progression. The objective of this proposal is to identify the mechanisms that generate synchronized rapid and ultradian insulin and glucagon oscillations from multiple islets. The central hypothesis is that multiple mechanisms working in concert produce both rapid and ultradian oscillations of hormone release. The rationale for performing this work is that a thorough understanding of the dynamics of glucose-regulatory hormone secretion will lead to the design of therapeutic approaches that alleviate the complications associated with diabetes and other metabolic diseases. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Determine the effect of time delays and dual entrainment on insulin synchronization, and 2) identify glucagon secretion and synchronization dynamics. Under the first aim, two methods for inducing islet synchronization will be used together, one a negative insulin/glucose feedback loop with time delays, and the other, pulsatile activation of M3 receptors. To accomplish this aim, a high-speed method for insulin measurement will be developed using droplet microfluidics and will be used for testing a range of time delays and the ability to perfuse multiple secretagogues in parallel. In the second aim, glucagon secretion will be measured for the first time from single islets of Langerhans using a homogeneous time resolved fluorescence assay using a microfluidic system. With this method, we anticipate observing single islet glucagon secretion dynamics and will parallelize the method to discern how glucagon pulses are synchronized across multiple islets. The proposed research is innovative because the microfluidic systems and measurement approaches developed in this proposal will allow rapid and ultradian oscillations of islet secretion to be observed for the first time. These results will provide a significant increase in the knowledge of islet regulation, which is crucial for fully understanding the mechanism of glucose homeostasis and how it goes awry in metabolic diseases. Ultimately, this knowledge has the potential to guide therapeutic development for reducing the problems associated with unregulated glucose levels in type II diabetes.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $360,267 )
2025	2025	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	17	5/20/2025	NON-COMPETING CONTINUATION	$360,267
														Subtotal = $360,267

Issue Date FY: 2024 ( Subtotal = $346,091 )
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	16	5/13/2024	NON-COMPETING CONTINUATION	$346,091
														Subtotal = $346,091

Issue Date FY: 2023 ( Subtotal = $360,755 )
2023	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	15	5/12/2023	NON-COMPETING CONTINUATION	$360,755
2023	2022	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	14	5/10/2023	COMPETING CONTINUATION	$281,846
2023	2020	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	5/10/2023	NON-COMPETING CONTINUATION	-$281,846
														Subtotal = $360,755

Issue Date FY: 2022 ( Subtotal = $324,397 )
2022	2022	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	14	5/31/2022	COMPETING CONTINUATION	$324,397
2022	2020	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	13	5/30/2022	NON-COMPETING CONTINUATION	$0
2022	2020	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	3/18/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $324,397

Issue Date FY: 2020 ( Subtotal = $356,418 )
2020	2020	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	3/24/2020	NON-COMPETING CONTINUATION	$356,418
														Subtotal = $356,418

Issue Date FY: 2019 ( Subtotal = $356,651 )
2019	2019	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	4/12/2019	NON-COMPETING CONTINUATION	$356,651
														Subtotal = $356,651

Issue Date FY: 2018 ( Subtotal = $356,883 )
2018	2018	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	3/5/2018	NON-COMPETING CONTINUATION	$321,194
2018	2018	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	11	4/30/2018	NON-COMPETING CONTINUATION	$35,689
														Subtotal = $356,883

Issue Date FY: 2017 ( Subtotal = $346,712 )
2017	2017	FLORIDA STATE UNIVERSITY, THE	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	3/29/2017	COMPETING CONTINUATION	$346,712
2017	2017	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	10	8/14/2017	COMPETING CONTINUATION	$262,815
2017	2016	FLORIDA STATE UNIVERSITY, THE	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	3/24/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
2017	2016	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	9	8/14/2017	EXTENSION WITH OR WITHOUT FUNDS	-$262,815
														Subtotal = $346,712

Issue Date FY: 2016 ( Subtotal = $330,600 )
2016	2016	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	3/17/2016	EXTENSION WITH OR WITHOUT FUNDS	$330,600
														Subtotal = $330,600

Issue Date FY: 2015 ( Subtotal = $330,600 )
2015	2015	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	3/13/2015	NON-COMPETING CONTINUATION	$330,600
														Subtotal = $330,600

Issue Date FY: 2014 ( Subtotal = $330,219 )
2014	2014	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	3/19/2014	NON-COMPETING CONTINUATION	$330,219
														Subtotal = $330,219

Issue Date FY: 2013 ( Subtotal = $329,078 )
2013	2013	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	3/15/2013	COMPETING CONTINUATION	$330,219
2013	2013	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	6	3/21/2013	COMPETING CONTINUATION	-$1,141
2013	2012	FLORIDA STATE UNIVERSITY	A22001 UNIVERSITY CENTER	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	3/13/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $329,078

Issue Date FY: 2012 ( Subtotal = $277,478 )
2012	2012	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	3/1/2012	NON-COMPETING CONTINUATION	$277,478
														Subtotal = $277,478

Issue Date FY: 2011 ( Subtotal = $278,448 )
2011	2011	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/2/2011	NON-COMPETING CONTINUATION	$253,135
2011	2011	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	6/2/2011	NON-COMPETING CONTINUATION	$25,313
														Subtotal = $278,448

Issue Date FY: 2010 ( Subtotal = $284,356 )
2010	2010	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	3/1/2010	NON-COMPETING CONTINUATION	$282,151
2010	2010	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	8/25/2010	NON-COMPETING CONTINUATION	$2,205
														Subtotal = $284,356

Issue Date FY: 2009 ( Subtotal = $285,820 )
2009	2009	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/27/2009	NON-COMPETING CONTINUATION	$285,820
														Subtotal = $285,820

Issue Date FY: 2008 ( Subtotal = $265,956 )
2008	2008	Florida State University	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/31/2008	NEW	$265,956
														Subtotal = $265,956

Grand Total All Awards = $5,520,729

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Microfluidic Devices For Determining Dynamics Of Islets of Langerhans

Award Number: R01DK080714

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2008

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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