Innovative Use of Glucagon Isotopes Enhances Understanding of Glucagon Metabolism in Type 1 Diabetes

A groundbreaking study led by Dr. Ananda Basu from the University of Alabama at Birmingham has introduced a novel approach to examining glucagon metabolism in humans, including those with and without Type 1 diabetes. Using innovative, non-radioactive stable glucagon tracers, researchers have, for the first time, characterized how glucagon is processed in different regions of the body. This research holds significant potential for advancing our understanding of pancreatic alpha cell function and the role of glucagon in metabolic regulation.

Glucagon, a hormone produced by pancreatic alpha cells, is vital for maintaining glucose balance and overall energy metabolism. In individuals with diabetes, especially Type 1, the regulation of glucagon secretion is often impaired, leading to challenges in blood sugar control and episodes of hyperglycemia or hypoglycemia.

The study employed sophisticated isotope modeling techniques combined with organ-specific balance methods to investigate glucagon metabolism in the splanchnic (abdominal) region and peripheral tissues like the legs. Researchers infused stable glucagon isotopes, such as [13C9, 15N1]-glucagon, at varying rates to mimic physiological conditions while measuring subsequent regional glucagon extraction and production.

Findings revealed that the splanchnic region's ability to extract glucagon did not differ significantly between healthy individuals and those with Type 1 diabetes. However, leg tissues showed a decrease in glucagon extraction with rising concentrations in healthy participants, a response that was absent in those with T1D. Notably, net splanchnic glucagon production remained stable during infusions across both groups.

This pioneering work highlights that peripheral tissues also actively extract glucagon, prompting further research into the mechanisms behind this process. The data has important implications for improving dual-hormone insulin delivery systems, which aim to prevent hypoglycemia by co-infusing glucagon, and for exploring emerging therapies involving G protein-coupled receptor agonists.

Overall, this research paves the way for enhanced understanding of regional glucagon metabolism, informing more precise treatments for diabetes and related metabolic disorders.

Source: https://medicalxpress.com/news/2025-06-glucagon-isotopes-metabolism-diabetes.html