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Cytoskeleton-mediated regulation of insulin secretion hot spots in pancreatic beta cells

Award Number: F31DK136344
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Cytoskeleton-mediated regulation of insulin secretion hot spots in pancreatic beta cells - Project Summary Insulin secretion from pancreatic β cells is crucial to maintaining blood glucose homeostasis, allowing cells throughout the body to take up glucose from the blood and obtain nutrients for normal cellular processes. In type 2 diabetes, however, peripheral tissues become insulin resistant, β cells over-secrete insulin to compensate, and eventually β cells become dysfunctional. It is therefore necessary to thoroughly understand the mechanisms of insulin secretion in order to identify potential therapeutic targets for type 2 diabetes treatment. Insulin secretion is known to predominantly occur at the vascular face of the β cell, at regions termed “hot spots.” Hot spots are characterized by proteins common to the active zone of neurons as well as proteins of cortical microtubule-stabilizing complexes and focal adhesions. Our laboratory has also found that microtubule destabilization promotes insulin secretion specifically at hot spots. Others have shown that the actin cytoskeleton also plays a critical regulatory role in insulin secretion. Given the known connections of microtubules, focal adhesions, and actin with known hot spot proteins, it is likely that the interplay of these cytoskeletal elements is essential for the hot spot organization and function. I therefore hypothesize that insulin secretion hot spots are “secreting adhesions”: mechanosensitive subcellular domains which use cytoskeletal regulation to accomplish directed and clustered secretion. My specific aims are to 1) characterize the cytoskeleton networks, their interplay, and other hot spot components in β cells; and to 2) test if MT- regulated RhoA-dependent contractility promotes clustered secretion via secreting adhesion assembly. To address these aims, I will use high- and super-resolution fixed and live-cell imaging techniques combined with computational analyses. Improving the understanding of hot spot identity and establishment via the cytoskeleton will contribute to overall knowledge of insulin secretion, and potentially uncover novel targets for diabetes therapeutics.


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 = $7,173 )
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	6/4/2025	NON-COMPETING CONTINUATION	$94
2025	2025	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/7/2025	NON-COMPETING CONTINUATION	$7,079
														Subtotal = $7,173

Issue Date FY: 2024 ( Subtotal = $34,250 )
2024	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	5/9/2024	NON-COMPETING CONTINUATION	$34,250
														Subtotal = $34,250

Issue Date FY: 2023 ( Subtotal = $32,970 )
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	4/7/2023	NEW	$0
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/7/2023	NEW	$32,970
														Subtotal = $32,970

Grand Total All Awards = $74,393

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Cytoskeleton-mediated regulation of insulin secretion hot spots in pancreatic beta cells

Award Number: F31DK136344

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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