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Identifying Gestational-induced Changes in Islet Macrophages as a Potential Target for Beta-cell Expansion

Award Number: F31GM150237
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/22/2024
PERIOD OF PERFORMANCE END DATE: 07/21/2026

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Identifying Gestational-induced Changes in Islet Macrophages as a Potential Target for Beta-cell Expansion - Abstract (30 line max) Diabetes mellitus is the leading cause of kidney failure, heart disease, and stroke, affecting 537 million people worldwide. Diabetes is diagnosed as an increase in blood glucose due to insufficient or ineffective insulin production by the pancreatic β-cell. The inability of the β-cell to adapt to changes in physiologic demand results in hyperglycemia. Under select conditions, such as injury and high-fat diet, the β-cell is capable of expansion, increasing in size and/or number to increase insulin production. Therefore, one potential strategy for mitigating hyperglycemic events is to stimulate β-cell replication. A crucial component for β-cell maturation and β-cell expansion in the adult pancreas is macrophages which support tissue growth through the production of cytokines and stimulatory factors. In models of injury, macrophages shift from their basal classically activated proinflammatory state to a more alternatively-activated anti-inflammatory state, supportive of tissue remodeling through the production of anti-inflammatory cytokines, such as TGF-β. Robust β-cell proliferation has also been measured during pregnancy as a result of reductions in insulin sensitivity and increased fetal demand, making pregnancy an ideal model for investigating expansion in mature β-cells under non-pathologic conditions. β-cell expansion during gestation and macrophage contribution to maternal β-cell growth has not been fully elucidated. I will assess changes in macrophage quantity and phenotype throughout pregnancy. I will determine the source of macrophage accumulation within the islet and whether it is a critical component for β-cell expansion in late gestation. I will also determine whether depletion of islet resident macrophages impairs β-cell expansion in late gestation. I hypothesize that pregnancy drives islet macrophages to an alternatively-activated phenotype, necessary for maternal β-cell expansion. To test this hypothesis, I will explore the following two aims: (1) Characterize the macrophage population within the islet throughout gestation. (2) Establish the requirement of macrophages for maternal β-cell expansion in late gestation. The completion of these aims will identify macrophage-specific responses during pregnancy and their effects on β-cell expansion. 1


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 = $42,491 )
2025	2025	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	2	8/15/2025	NON-COMPETING CONTINUATION	$42,491
														Subtotal = $42,491

Issue Date FY: 2024 ( Subtotal = $41,927 )
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	001	1	1/22/2024	NEW	$0
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	000	1	1/22/2024	NEW	$40,647
2024	2024	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Biomedical Research and Research Training	002	1	6/11/2024	NEW	$1,280
														Subtotal = $41,927

Grand Total All Awards = $84,418

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Identifying Gestational-induced Changes in Islet Macrophages as a Potential Target for Beta-cell Expansion

Award Number: F31GM150237

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/22/2024

PERIOD OF PERFORMANCE END DATE: 07/21/2026

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