Glibenclamide prevents hypoglycemia-induced fatal cardiac arrhythmias in rats

Candace M. Reno, Justin Bayles, Allie Skinner, Simon J. Fisher

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Sulfonylureas increase the incidence of severe hypoglycemia in people with type 2 diabetes and might increase the risk of sudden cardiac death. Sulfonylureas stimulate insulin secretion by closing pancreatic ATP-sensitive potassium ion (KATP) channels. To investigate the role of KATP channel modulators on cardiac arrhythmias and mortality in the setting of severe hypoglycemia, adult Sprague-Dawley rats underwent hyperinsulinemic (0.2 U/kg/min) severe hypoglycemic (10 to 15 mg/dL) clamps with continuous electrocardiography. The rats were randomized for treatment with intravenous vehicle (VEH), the sulfonylurea glibenclamide (GLIB; KATP channel blocker; 5 mg/kg/h), or diazoxide (DIAZ; KATP channel opener; 5 mg/kg/h). The results demonstrated that GLIB completely prevented first-degree heart block compared with VEH (0.18 6 0.09/min) and DIAZ (0.2 6 0.05/min). Second-degree heart block was significantly reduced with GLIB (0.12 6 0.1/min) compared with VEH (0.6 6 0.2/min) and DIAZ (6.9 6 3/min). The incidence of third-degree heart block was completely prevented by GLIB compared with VEH (67%) and DIAZ (87.5%). Hypoglycemiainduced mortality was completely prevented by GLIB compared with VEH (60%) and DIAZ (82%). In conclusion, although GLIB increases the risk of hypoglycemia by increasing insulin secretion, these results have demonstrated a paradoxical protective role of GLIB against severe hypoglycemiainduced fatal cardiac arrhythmias.

Original languageEnglish
Pages (from-to)2614-2620
Number of pages7
Issue number7
StatePublished - Jul 1 2018

Bibliographical note

Funding Information:
Financial Support: The authors acknowledge funding from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (Grant 5T32DK091317 to C.M.R. and Grant R01 NS070235 to S.J.F.), the Juvenile Diabetes Research Foundation International (Grant 3-APF-2017-407-A-N to C.M.R.), and funding from the University of Utah’s Diabetes and Metabolism Research Center.

Publisher Copyright:
© 2018 Endocrine Society.

ASJC Scopus subject areas

  • Endocrinology


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