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Targeting BNC2 Neurons for Diabetes Treatment

Award Number: K01DK143200
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 02/28/2030

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Targeting BNC2 Neurons for Diabetes Treatment - Project Summary: Chronic metabolic diseases, such as diabetes, are major global health threats and one of the most pressing and costly biomedical challenges today. Developing more effective treatments is essential. Accumulating evidence suggests that the brain, particularly the hypothalamus, plays a vital role in regulating glucose homeostasis. Hypothalamus dysfunction significantly contributes to diabetes. Furthermore, targeting the hypothalamus, especially the arcuate nucleus, shows promise in improving diabetic conditions. Despite its significance, the role of the brain in glucose homeostasis and diabetes pathogenesis remains poorly understood. Recent findings have identified a previously uncharacterized population of leptin receptor-expressing neurons, termed basonuclin 2 (BNC2) neurons, within the hypothalamic arcuate nucleus. These neurons have been implicated in rapid satiety regulation and energy balance, addressing a critical gap in the understanding of hypothalamic control of feeding behavior. Notably, preliminary data suggest that BNC2 neuron activity directly influences peripheral glycemia. Furthermore, genome-wide association studies (GWAS) have established a significant correlation between the Bnc2 gene and metabolic disorders, including diabetes and obesity, underscoring the relevance of BNC2 neurons in metabolic homeostasis and their potential as therapeutic targets. This study aims to elucidate the role of BNC2 neurons in glucose regulation and evaluate their therapeutic potential in diabetes and insulin resistance. Glucose homeostasis is primarily coordinated by hormone-secreting endocrine cells in the pancreas and by glucose production and utilization in peripheral tissues like the liver, muscle, and adipose tissue. Preliminary data suggest that activating BNC2 neurons impacts the function of specific metabolic processes and target organs. To further investigate these mechanisms, this study will first determine whether BNC2 neurons influence target organ function through direct neuronal connections. Next, the molecular pathways underlying BNC2 neuron regulation of these organs will be elucidated. Multiplexed single-nucleus RNA sequencing (snRNA-seq) will be employed to profile cell-specific changes in target organs induced by BNC2 neuronal activity, followed by functional validation using genetic tools. Lastly, the impact of BNC2 neuron modulation on glucose metabolism will be evaluated in diabetic and insulin-resistant conditions using mouse models of both type 1 and type 2 diabetes. Altogether, the successful completion of this project will provide mechanistic insights into how BNC2 neurons regulate glucose homeostasis and potentially identify new therapeutic avenues for diabetes and insulin resistance.


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 = $132,423 )
2026	2026	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/13/2026	NEW	$132,423
														Subtotal = $132,423

Grand Total All Awards = $132,423

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Targeting BNC2 Neurons for Diabetes Treatment

Award Number: K01DK143200

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 02/28/2030

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