Recurrent hypoglycaemia leads to impairment in glucagon‐mediated hepatic glycogenolysis in type 1 diabetic mice
Year: 2025
Type: article
Abstract: AIMS: To explore the alterations in pancreatic α cells and hepatic glycogen metabolism in mice with type 1 diabetes mellitus (T1DM) following recurrent hypoglycaemia, aiming to elucidate the underlying mechanisms that contribute to impaired counterregulatory responses to hypoglycaemia. MATERIALS/METHODS: The alterations in pancreatic α cells and hepatic glycogenolysis were assessed in T1DM mice experiencing recurrent hypoglycaemia induced by insulin. Furthermore, glucagon intervention experiments were conducted on T1DM mice subjected to recurrent hypoglycaemia and on their primary hepatocytes to clarify further the mechanisms responsible for the observed changes in hepatic glycogenolysis. RESULTS: In T1DM mice, recurrent hypoglycaemia led to a reduction of pancreatic α cell mass and a decrease in glucagon synthesis and secretion by these cells, indicating a compromised counterregulatory response to hypoglycaemia. Furthermore, repeated hypoglycaemic episodes disrupted hepatic glycogenolysis, thereby diminishing the liver's ability to respond to hypoglycaemia. The observed decrease in the expression of hepatic glucagon receptors was closely associated with the impairment of hepatic glycogenolysis, ultimately leading to a reduced hyperglycaemic effect of exogenous glucagon. CONCLUSIONS: Pancreatic α cells play a significant role in developing hypoglycaemic counterregulatory impairment induced by recurrent hypoglycaemia; however, the liver's role is even more critical. Recurrent hypoglycaemia can lead to a reduction in the expression of glucagon receptors in the liver, resulting in impaired hypoglycaemic counterregulation.
Source: Diabetes Obesity and Metabolism
DOI: 10.1111/dom.16409
Authors: Min‐Ne Li, Fang‐Xin Jin, Jing‐Jing Zhao, Yan Wang, Bao‐Xiang Zhuang, Ru‐Jiang Li
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Award: G3704794936
OpenAlex ID: W4409618428