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Regulation of spatial organization and cell-cell communication in the islet of Langerhans

Award Number: R01DK121706
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: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2029

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Regulation of spatial organization and cell-cell communication in the islet of Langerhans - The most important determinant in whether a person will develop type 2 diabetes or gestational diabetes is whether their islets of Langerhans are able to compensate for the increase demand for insulin brought about by peripheral insulin resistance. In successful compensatory islet expansion (that can mitigate the develop- ment of diabetes), islets retain their three-dimensional architecture, endocrine cell-cell communication, and in- tra-islet regulation of hormone secretion. Failure of compensatory islet expansion is a key event in the etiology of type 2 diabetes and gestational diabetes. Accordingly, abnormal islet architecture and dysregulated hor- mone secretion are hall-marks of all types of diabetes mellitus. How islets orchestrate the changes in tissue architecture and in cell-cell communication during compensatory expansion, and why they fail to do so in dia- betes, is unclear. This is important, because approaches to promoting compensatory islet expansion by focus- ing on β cell proliferation alone, without tackling other aspects of islet tissue remodeling, have not been suffi- ciently effective so far. This application focuses on the Slit-Robo signaling pathway as a critical regulatory mechanism in remodeling islet organization and intra-islet cell-cell communication, the failure of which is a lim- iting factor for compensatory islet expansion. Specific Aim 1 will test the hypothesis that down-regulation of Robo2 receptors in beta cells is essential for compensatory islet expansion. Specific Aim 2 will determine how down-regulation of Robo2 in beta cells causes alpha cells dyregulation. Specific Aim 3 will test the hypothesis that Slit-Robo mediated crosstalk between pancreatic stroma and endocrine cells is involved in compensatory islet expansion. Understanding the role of Slit-Robo signaling in regulating islet dynamics during life events could potentially be leveraged in the future to promote successful compensatory islet expansion and intra-islet control of hormone secretion in obesity, insulin resistance, and pregnancy.


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: 2026 ( Subtotal = $688,170 )
2026	2026	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	12/5/2025	NON-COMPETING CONTINUATION	$688,170
														Subtotal = $688,170

Issue Date FY: 2025 ( Subtotal = $688,170 )
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	6	5/28/2025	COMPETING CONTINUATION	$89,461
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	11/22/2024	COMPETING CONTINUATION	$598,709
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	6	1/8/2025	COMPETING CONTINUATION	$0
2025	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	11/18/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $688,170

Issue Date FY: 2023 ( Subtotal = $382,090 )
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	5/26/2023	NON-COMPETING CONTINUATION	$382,090
														Subtotal = $382,090

Issue Date FY: 2022 ( Subtotal = $382,090 )
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	7/1/2022	NON-COMPETING CONTINUATION	$382,090
														Subtotal = $382,090

Issue Date FY: 2021 ( Subtotal = $382,090 )
2021	2021	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/11/2021	NON-COMPETING CONTINUATION	$382,090
														Subtotal = $382,090

Issue Date FY: 2020 ( Subtotal = $380,900 )
2020	2020	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	5/11/2020	NON-COMPETING CONTINUATION	$380,900
														Subtotal = $380,900

Issue Date FY: 2019 ( Subtotal = $380,900 )
2019	2019	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	5/20/2019	NEW	$380,900
														Subtotal = $380,900

Grand Total All Awards = $3,284,410

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Regulation of spatial organization and cell-cell communication in the islet of Langerhans

Award Number: R01DK121706

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: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2029

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