Monday, July 7, 2025 7/7/2025

Mechanism for Reduced Adrenomedullary Epinephrine Release in Type 1 Diabetes

Award Number: F31DK086681
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2010
PERIOD OF PERFORMANCE END DATE: 06/30/2013

Group Awards By:

View Award Description

Mechanism for Reduced Adrenomedullary Epinephrine Release in Type 1 Diabetes - DESCRIPTION (provided by applicant): Release of glucagon, a principal hormone underlying the normal counter-regulatory response (CRR) to acute hypoglycemia is largely absent in type 1 diabetes mellitus (T1DM). In its absence, other circulating CRR hormones, such as epinephrine, take on primary importance in restoring plasma glucose to basal levels. However, epinephrine release in response to hypoglycemia is also attenuated in T1DM, making diabetic patients particularly prone to asymptomatic hypoglycemia that, if untreated, can lead to coma and death. This defect has been minimally studied at the level of the adrenal medulla (AM) which produces most of all circulating epinephrine in the body. Chromaffin cells in the AM synthesize epinephrine and release it when activated by the central nervous system or other circulating hormones. Our preliminary data show that muscarinic acetylcholine receptor (mAchR) signaling is impaired in adrenomedullary chromaffin cells isolated from streptozocin (STZ)-treated diabetic rats and that type 3 mAchR, a predominant receptor subtype in the adrenal medulla, is internalized to a much greater degree in diabetic chromaffin cells than in controls. These data led me to hypothesize that internalization of adrenomedullary mAchR in T1DM reduces epinephrine release in response to hypoglycemia. To test this hypothesis, I plan to: (1) Determine the time after the on-set of diabetes when this defect occurs, the extent of the reduction, the specificity of the deficit and the involvement of diabetic hyperglycemia and hypoinsulinemia in its development. The STZ model of diabetes will be used in these studies. In vivo experiments will be performed to study the development of reduced adrenomedullary response to hypoglycemic and non-hypoglycemic stimuli during T1DM. Isolated adrenal glands and enzymatically- isolated chromaffin cells will be used to evaluate the contributions of nicotinic and muscarinic acetylcholine signaling and adrenal epinephrine content to this deficit. (2) Investigate the functional properties of acetylcholine receptors in adrenomedullary chromaffin cells during STZ-induced diabetes by measuring mRNA, protein levels, cellular localization and functional properties of nicotinic and muscarinic acetylcholine receptor subtypes in chromaffin cells from diabetic animals. The results of the proposed experiments will establish the cellular basis for the adrenal medullary defect in epinephrine release that contributes to the reduced CRR in T1DM. Health relevance: This project seeks to investigate the cellular basis for defective regulation of the body's response to low blood glucose in diabetic patients. This defect limits insulin-based therapies. PUBLIC HEALTH RELEVANCE: This project seeks to investigate the cellular basis for defective regulation of the body's response to low blood glucose in diabetic patients. This defect limits insulin-based therapies.


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: 2017 ( Subtotal = -$12,943 )
2017	2012	UNIVERSITY OF MEDICINE AND DENTISTRY OF NJ (INC)							Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	4/18/2017	NON-COMPETING CONTINUATION	-$1
2017	2012	UNIVERSITY OF MEDICINE AND DENTISTRY OF NJ (INC)							Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/18/2017	NON-COMPETING CONTINUATION	-$12,942
														Subtotal = -$12,943

Issue Date FY: 2012 ( Subtotal = $31,060 )
2012	2012	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/10/2012	NON-COMPETING CONTINUATION	$31,060
														Subtotal = $31,060

Issue Date FY: 2011 ( Subtotal = $30,398 )
2011	2011	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/5/2011	NON-COMPETING CONTINUATION	$30,398
														Subtotal = $30,398

Issue Date FY: 2010 ( Subtotal = $29,759 )
2010	2010	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/23/2010	NEW	$29,759
														Subtotal = $29,759

Grand Total All Awards = $78,274

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanism for Reduced Adrenomedullary Epinephrine Release in Type 1 Diabetes

Award Number: F31DK086681

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2010

PERIOD OF PERFORMANCE END DATE: 06/30/2013

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer