Vitamin E treatment in insulin-deficient diabetic rats reduces cardiac arrhythmias and mortality during severe hypoglycemia

Candace M. Reno-Bernstein, Milan Oxspring, Justin Bayles, Emily Yiqing Huang, Ivana Holiday, Simon J. Fisher

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

In people with type 1 diabetes, hypoglycemia can induce cardiac arrhythmias. In rodent experiments, severe hypoglycemia can induce fatal cardiac arrhythmias, especially so in diabetic models. Increased oxidative stress associated with insulin-deficient diabetes was hypothesized to increase susceptibility to severe hypoglycemia-induced fatal cardiac arrhythmias. To test this hypothesis, Sprague–Dawley rats were made insulin deficient with streptozotocin and randomized into two groups: 1) control (n = 22) or 2) vitamin E treated (four doses of a-tocopherol, 400 mg/kg, n = 20). Following 1 week of treatment, rats were either tested for cardiac oxidative stress or underwent a hyperinsulinemic-severe hypoglycemic (10–15 mg/dL) clamp with electrocardiogram recording. As compared with controls, vitamin E-treated rats had threefold less cardiac oxidative stress, sixfold less mortality due to severe hypoglycemia, and sevenfold less incidence of heart block. In summary, vitamin E treatment and the associated reduction of cardiac oxidative stress in diabetic rats reduced severe hypoglycemia-induced fatal cardiac arrhythmias. These results indicate that in the setting of diabetes, pharmacological treatments that reduce oxidative stress may be an effective strategy to reduce the risk of severe hypoglycemia-induced fatal cardiac arrhythmias. NEW & NOTEWORTHY For people with type 1 diabetes, severe hypoglycemia can be fatal. We show in our animal model that insulin-deficient diabetic rats have fatal cardiac arrhythmias during severe hypoglycemia that are associated with increased cardiac oxidative stress. Importantly, treatment with vitamin E, to reduce oxidative stress, decreased fatal cardiac arrhythmias during severe hypoglycemia.

Original languageEnglish
Pages (from-to)E428-E434
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume323
Issue number5
DOIs
StatePublished - Nov 2022

Bibliographical note

Publisher Copyright:
© 2022 the American Physiological Society.

Keywords

  • animal model
  • cardiac arrhythmias
  • diabetes
  • hypoglycemia
  • vitamin E

ASJC Scopus subject areas

  • General Medicine

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