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Sensory Neuromodulation of Pancreatic Beta Cells

Award Number: R01DK122167
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: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Sensory Neuromodulation of Pancreatic Beta Cells - The demise of pancreatic islet insulin-secreting β cells in diabetes has a neuronal component. Therefore, understanding the biology underlying the neuronal control of islet β cells will unravel information that can be leveraged to develop neuromodulation-based methods to enhance functional β-cell mass in individuals with diabetes. The pancreas receives a generous supply of efferent parasympathetic and sympathetic neurons and afferent sensory neurons. While the effect of efferent neurons in islet β cells is well documented, the role of sensory neurons is largely unknown. The pancreatic sensory neurons emanate from the vagal and thoracic spinal nerves with cell bodies lying in the nodose ganglia (NG) and dorsal root ganglia (DRG), respectively. Using chemical and surgical denervation models, we demonstrated that ablation of a subset of DRG pancreas-projecting sensory neurons enhanced glucose-stimulated insulin secretion and glucose excursion – in a sex-dependent manner – without alterations in insulin sensitivity, body composition and energy expenditure. These data prompted us to determine the molecular foundation of the crosstalk between sensory neurons and pancreatic β cells under normal and metabolically challenged conditions. First, we will use live-cell imaging of intracellular calcium influx, proteomics and in vitro co-culture systems to delineate the cellular and molecular mechanisms of the sensory neuron-islet crosstalk. We will use in vitro and in vivo models to interrogate the significance of the neuro-islet intercommunication in the well-known sex difference in glucose homeostasis. Second, we will use high-throughput RNA deep sequencing approach to identify vagal and spinal sensory-derived neuropeptides and growth factors modulating adaptive β-cell expansion and activity in insulin-resistant states. High-resolution imaging modality (PanCLARITY) will be used to map with accuracy the interactions between pancreatic β cells and the newly identified sensory neuronal markers. Finally, we will use in vitro and in vivo models to define the role and mechanism of action of novel sensory-derived signaling molecules in proliferation and function of mouse and human β cells. Together, these studies will unravel the molecular foundation of the unique interactions between afferent neurons and islet β cells and will provide high-value biological data to design neuropharmacology- and neuromodulation-based strategies to enhance functional β-cell mass in patients with 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 = $0 )
2025	2024	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	6/30/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $393,600 )
2024	2024	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	5	7/19/2024	NON-COMPETING CONTINUATION	$393,600
2024	2023	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	5/23/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$65,273
2024	2023	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	4	7/18/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2022	RUTGERS, THE STATE UNIVERSITY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/23/2024	NON-COMPETING CONTINUATION	-$65,273
														Subtotal = $393,600

Issue Date FY: 2023 ( Subtotal = $410,000 )
2023	2023	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	9/6/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$410,000
2023	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	9/5/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $410,000

Issue Date FY: 2022 ( Subtotal = $392,500 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/7/2022	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2021 ( Subtotal = $392,500 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	6/16/2021	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2020 ( Subtotal = $390,000 )
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/28/2020	NEW	$390,000
														Subtotal = $390,000

Grand Total All Awards = $1,978,600

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Sensory Neuromodulation of Pancreatic Beta Cells

Award Number: R01DK122167

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: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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