{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:56:22Z","timestamp":1771048582209,"version":"3.50.1"},"reference-count":48,"publisher":"Baishideng Publishing Group Inc.","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Diabetes"],"abstract":"BACKGROUND<\/jats:p>\n Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions. However, the patho-genesis of hypoglycaemic counterregulation is still unclear. Glucagon-like peptide-1 (GLP-1) and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus (T1DM). The role of GLP-1 in counterregulatory dys-function during hypoglycaemia in patients with T1DM has not been reported.<\/jats:p>\n AIM<\/jats:p>\n To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice.<\/jats:p>\n METHODS<\/jats:p>\n T1DM was induced in C57BL\/6J mice using streptozotocin, followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia (DH5). Immunofluorescence, Western blot, and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon (GCG) secretion. The GLP-1 receptor agonist GLP-1(7-36) or the antagonist exendin (9-39) were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice.<\/jats:p>\n RESULTS<\/jats:p>\n The expression levels of intestinal GLP-1 and its receptor (GLP-1R) were significantly increased in DH5 mice. Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex, leading to dysfunction of adrenal counterregulation during hypoglycaemia. DH5 mice showed increased pancreatic \u03b4-cell mass, cAMP levels in \u03b4 cells, and plasma somatostatin concentrations, while cAMP levels in pancreatic \u03b1 cells and plasma GCG levels decreased. Furthermore, GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group. Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway.<\/jats:p>\n CONCLUSION<\/jats:p>\n Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia, leading to reduced appetite and compromised secretion of adrenaline, noradrenaline, and GCG during hypo-glycaemia.<\/jats:p>","DOI":"10.4239\/wjd.v15.i8.1764","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T23:57:57Z","timestamp":1721951877000},"page":"1764-1777","source":"Crossref","is-referenced-by-count":11,"title":["Intestinal glucagon-like peptide-1: A new player associated with impaired counterregulatory responses to hypoglycaemia in type 1 diabetic 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