# The Role of Ventromedial Hypothalamus Cholecystokinin Receptor B Containing Neurons in Regulation of Hypoglycemia and Hypoglycemia-Associated Autonomic Failure

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $71,430

## Abstract

PROJECT ABSTRACT
 Approximately 30.1 million people in the United States suffer from diabetes and our most powerful anti-
diabetic medications increase the risk for hypoglycemia. In addition to interfering with the intensity of insulin
therapy and glycemic control, severe hypoglycemia causes 4-10% of deaths in patients with type 1 diabetes.
One episode of hypoglycemia increases the risk of recurrent hypoglycemia (RH) and can promote hypoglycemia
associated autonomic failure (HAAF), which impairs the activation of the sympathetic nervous system and the
release of glucose-mobilizing hormones by which the counter-regulatory response (CRR) combats
hypoglycemia. The ventromedial hypothalamic nucleus (VMN) represents a crucial mediator of the CRR, but
contains many distinctly-acting neural populations. The molecular identity of the CRR-mediating VMN neurons
has remained undefined, preventing their study. Recent work in the Myers lab has revealed that the
cholecystokinin b receptor (CCKBR)-expressing subpopulation of VMN neurons (VMNCCKBR cells) mediate the
CRR: activating these cells increases blood glucose, while silencing them abrogates the CRR. Importantly, we
also found that RH impairs the ability of VMNCCKBR neurons to raise blood glucose. The goals of this proposal
are to understand the regulation of VMNCCKBR neurons and to test the hypothesis that the lesion in HAAF lies
within the VMNCCKBR neural circuitry. We aim to define the afferent and direct mechanisms by which
hypoglycemia activates VMNCCKBR neurons and the potential dysregulation of these systems by HAAF. These
studies will reveal the neural mechanisms that mediate the CRR and will provide insight into the pathophysiology
of HAAF, thus permitting the design of treatments to prevent severe hypoglycemia and permit tight glycemic
control.
 As a physician-scientist, my desire to improve the care of my patients and advance medical science
drives my research focus. I aim to become an independent investigator studying the neuronal networks that
contribute to the control of blood glucose and which may be pathophysiologically altered in diabetes and related
metabolic diseases. The work proposed in this application will allow to me develop the technical skills and
conceptual framework to ask important questions about the central control of metabolism, complementing the
molecular biology and genetic techniques that I developed during my graduate work. Training in the Myers lab
at the University of Michigan provides many opportunities for professional development, including interactions
with other leading scientists in the field (via seminars, research presentations and lab meetings) and guided
experiences with grant writing, paper writing and reviewing scientific journal articles. I will also receive guidance
through the University of Michigan Department of Internal Medicine Physician Scientist Training Program
(PSTP), which provides support through regular peer and faculty meetings and is committ...

## Key facts

- **NIH application ID:** 9989603
- **Project number:** 5F32DK122660-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Alison Holley Affinati
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $71,430
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989603

## Citation

> US National Institutes of Health, RePORTER application 9989603, The Role of Ventromedial Hypothalamus Cholecystokinin Receptor B Containing Neurons in Regulation of Hypoglycemia and Hypoglycemia-Associated Autonomic Failure (5F32DK122660-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9989603. Licensed CC0.

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