Rocha GR, de Melo FF. Glucagon-like peptide-1 and impaired counterregulatory responses to hypoglycemia in type 1 diabetes. World J Diabetes 2025; 16(2): 99928 [DOI: 10.4239/wjd.v16.i2.99928]
Corresponding Author of This Article
Fabrício Freire de Melo, PhD, Adjunct Professor, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Rua Hormindo Barros, 58, Quadra 17, Lote 58, Vitória da Conquista 45065-430, Bahia, Brazil. freiremeloufba@gmail.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Feb 15, 2025; 16(2): 99928 Published online Feb 15, 2025. doi: 10.4239/wjd.v16.i2.99928
Glucagon-like peptide-1 and impaired counterregulatory responses to hypoglycemia in type 1 diabetes
Gabriel Reis Rocha, Fabrício Freire de Melo
Gabriel Reis Rocha, Fabrício Freire de Melo, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45065-430, Bahia, Brazil
Author contributions: Rocha GR and de Melo FF contributed to review of the literature, and writing and editing of the manuscript; Rocha GR designed the overall concept and outline of the manuscript; de Melo FF contributed discussions for important intellectual concepts and design of the manuscript.
Supported by the Industrial Technological Initiation Scholarship of National Council for Scientific and Technological Development, CNPq, No. 0932204294929829; and the CNPq Research Productivity Fellow, No. 4357511882624145.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fabrício Freire de Melo, PhD, Adjunct Professor, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Rua Hormindo Barros, 58, Quadra 17, Lote 58, Vitória da Conquista 45065-430, Bahia, Brazil. freiremeloufba@gmail.com
Received: August 4, 2024 Revised: October 25, 2024 Accepted: November 4, 2024 Published online: February 15, 2025 Processing time: 149 Days and 5.7 Hours
Abstract
This letter comments on a study by Jin et al, published recently in the World Journal of Diabetes. Hypoglycemia is a significant complication of diabetes, with primary defense mechanisms involving the stimulation of glucagon secretion in α-cells and the inhibition of insulin secretion in pancreatic β-cells, which are often compromised in type 1 diabetes mellitus (T1DM) and advanced type 2 diabetes mellitus. Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness, a condition underpinned by complex pathophysiological processes, encompassing central nervous system adaptations and several hormonal interactions, including a potential role for glucagon-like peptide-1 (GLP-1) in paracrine and endocrine vias. Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreatic δ-cells, which inhibits glucagon secretion from neighboring α-cells. However, current trials evaluating GLP-1 receptor agonists (GLP-1 RAs) in T1DM patients have shown promising benefits in reducing insulin requirements and body weight, without increasing the risk of hypoglycemia. Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex, and their impact on hypoglycemia unawareness in T1DM patients.
Core Tip: Hypoglycemia is a common and significant phenomenon in type 1 diabetes, with recurrent episodes causing progressive dysfunction in glycemic counterregulation and reduced hypoglycemia awareness. The involvement of glucagon-like peptide 1 in this impairment is under investigation, but the pathophysiology is complex and multifactorial, involving various hormones and central receptors. Notwithstanding, studies on glucagon-like peptide 1 receptor agonists in type 1 diabetes mellitus have shown promising benefits and a favorable safety profile.
