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Establishing the Cholinergic Anti-Inflammatory Pathway in Pancreatic Islets.

Award Number: F30DK146476
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: 09/30/2026
PERIOD OF PERFORMANCE END DATE: 09/29/2028

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Establishing the Cholinergic Anti-Inflammatory Pathway in Pancreatic Islets. - PROJECT SUMMARY Type 1 Diabetes (T1D) is characterized by autoimmune destruction of insulin-producing beta cells within the pancreatic islets. Resident macrophages in the islets play a key role in maintaining tissue homeostasis but can also promote inflammation. The cholinergic anti-inflammatory reflex, known to suppress inflammation, may influence islet macrophages, but direct cholinergic innervation has not been established. This project aims to determine whether local cholinergic innervation suppresses islet macrophage activation. Preliminary data indicate that cholinergic neurons target resident macrophages and that macrophages express acetylcholine receptors. Additionally, acetylcholine agonists reduce macrophage activation in living pancreatic slices. We hypothesize that cholinergic innervation directly modulates macrophage activity, protecting islets from autoimmune initiation, which may be particularly effective in early stages of T1D. Specific Aim 1: Establish that local cholinergic neurons functionally regulate islet macrophages by structural and molecular interactions using immunohistochemistry and rtPCR and functional assays in living pancreas slices. Specific Aim 2: Test whether inhibition of local cholinergic neurons accelerates diabetes incidence in the non-obese diabetes mouse model. I will evaluate the effects of acetylcholine on islet inflammation, function, and diabetes progression, focusing on macrophage-specific responses through targeted inhibition of nicotinic signaling. By elucidating the cholinergic regulation of islet macrophages, this study aims to identify a novel anti-inflammatory pathway in T1D, with potential therapeutic applications for preserving beta cell function.


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 = $55,114 )
2026	2026	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/3/2026	NEW	$55,114
2026	2026	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	8/3/2026	NEW	$0
														Subtotal = $55,114

Grand Total All Awards = $55,114

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Establishing the Cholinergic Anti-Inflammatory Pathway in Pancreatic Islets.

Award Number: F30DK146476

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: 09/30/2026

PERIOD OF PERFORMANCE END DATE: 09/29/2028

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