# Targeting Ascending Catecholamine Pathways to Prevent Hypoglycemia

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $386,250

## Abstract

PROJECT SUMMARY / ABSTRACT
Diabetes is one of the leading causes of death, affecting more than 30 million people in the U.S., with one in four
individuals over 65 years suffering from its debilitating symptoms. Economically, diabetes represents an
enormous burden due to associated healthcare cost and loss of productivity. Insulin is the most effective
treatment used by many diabetic patients. However, achieving euglycemic balance can be a challenge since
therapeutic insulin often leads to unintended sharp drop in blood glucose level, causing severe hypoglycemia
which, if not addressed, may result in coma and death. Frequent hypoglycemia is one of the most reliable
predictor of malignant disease course and mortality in diabetes. Normally, hypoglycemia is averted by
counterregulary response pathway in the brain, which coordinates a series of physiological measures, along with
hunger, to restore blood glucose. However, recurrent hypoglycemic episodes, due to intensive insulin therapy
and daily activities, impairs these brain pathways, leaving diabetic patients vulnerable to subsequent
hypoglycemia. Efforts to identify the central counterregulatory pathways revealed essential role of brainstem
catecholamine neurons. We and others have shown that these neurons project extensively to hypothalamus,
and these projections are essential for their counterregulatory actions. However, hypothalamic target(s) of these
neurons and the mechanism(s) underlying their impairment by repeated hypoglycemia has not been determined.
The overall goal of this proposal is to identify the neural circuit(s) mediating counterregulatory actions of
brainstem catecholamine neurons. The aims of this grant are to 1) determine the direct neuronal target(s) of
medullary catecholamine neurons in the hypothalamus mediating counterregulation, and 2) determine how
repeated hypoglycemic episodes desensitize communication in this pathway. To accomplish these aims, we will
use axons of medullary catecholamine neurons as a map to downstream circuits. These studies will provide new
fundamental insights into the central counterregulatory pathways. In addition, by identifying mechanism of
impaired counterregulation, these studies may lead to novel therapeutic targets for the treatment of
hypoglycemia associated autonomic failure and hypoglycemia unawareness.

## Key facts

- **NIH application ID:** 10096388
- **Project number:** 1R01DK126740-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Deniz Atasoy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,250
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10096388

## Citation

> US National Institutes of Health, RePORTER application 10096388, Targeting Ascending Catecholamine Pathways to Prevent Hypoglycemia (1R01DK126740-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10096388. Licensed CC0.

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