# Developmental functions of adrenergic signaling in the pancreas

> **NIH NIH F32** · JOHNS HOPKINS UNIVERSITY · 2020 · $55,102

## Abstract

PROJECT SUMMARY
 Diabetes is a disease that affects millions worldwide, and results from an inability to regulate blood
glucose. β-cells residing in the islets of Langerhans in the pancreas control glucose levels through synthesis
and secretion of insulin. However, this ability is lost in diabetes due to dysfunction or loss of β-cells. Better
understanding of the mechanisms that control β-cell development and function will inform the treatment of
diabetes. β-adrenergic receptors are key mediators of physiological responses to the sympathetic nervous
system, and are abundantly expressed in the pancreas throughout life. However, the functions of adrenergic
receptors in pancreas development have not been studied. This has significant public health implications as β-
adrenergic receptor antagonists (β-blockers) are used to treat cardiovascular disease and hypertension in
pregnant mothers, but the effects on fetal development remain unknown. Additionally, chronic inhibition of β-
adrenoreceptors has adverse side-effects on glucose regulation and is a diabetes risk factor, but the
underlying mechanisms have not been identified. Thus, there is a critical need to understand the essential
roles of β-adrenergic receptors in both islet development and glucose homeostasis.
 Preliminarily, we have identified a tissue-specific role for the β-2 adrenergic receptor (Adrb2) in the
development of the pancreatic islets of Langerhans, potentially by limiting vascular growth. We also find that
pancreas-specific deletion of Adrb2 elicits functional defects in glucose tolerance and insulin secretion in
mature mice. The overall goal of this proposal is to identify and characterize the mechanisms by which
pancreas-specific Adrb2 expression controls islet development and glucose homeostasis. In Aim 1, we will
assess the consequences of pancreas-specific Adrb2 deletion on islet morphology and vascularization, and
define the signaling mechanisms by which Adrb2 regulates islet development. In Aim 2, we will address the
effects of pancreas-specific Adrb2 loss on glucose homeostasis and insulin secretion in mature animals, and
we will identify the molecular mechanisms by which Adrb2 signaling in β-cells influences insulin secretion. This
study is the first to address developmental functions of β-adrenergic receptors in islets, classically studied in
adult physiological responses, and to define a pancreas-specific role for β-adrenergic signaling in glucose
homeostasis. Our findings have the potential to establish a new line of research in current translational efforts
to treat metabolic disorders.

## Key facts

- **NIH application ID:** 9896821
- **Project number:** 5F32DK116482-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Eugene Eng Lin
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $55,102
- **Award type:** 5
- **Project period:** 2018-04-01 → 2021-01-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896821

## Citation

> US National Institutes of Health, RePORTER application 9896821, Developmental functions of adrenergic signaling in the pancreas (5F32DK116482-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9896821. Licensed CC0.

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