JUHL, CHRISTIAN R.;
BURGDORF, JOSEPHINE;
KNUDSEN, CECILIE;
VEEDFALD, SIMON;
HOLST, JENS J.;
KANTERS, JØRGEN;
TOREKOV, SIGNE S.
1785-P: Drug-Induced Blockade of the Herg-Voltage-Gated Potassium Channel Decreases Glucose-Stimulated Insulin and GLP-1 Secretion in Healthy Participants: A Crossover Study
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Media type:
E-Article
Title:
1785-P: Drug-Induced Blockade of the Herg-Voltage-Gated Potassium Channel Decreases Glucose-Stimulated Insulin and GLP-1 Secretion in Healthy Participants: A Crossover Study
Contributor:
JUHL, CHRISTIAN R.;
BURGDORF, JOSEPHINE;
KNUDSEN, CECILIE;
VEEDFALD, SIMON;
HOLST, JENS J.;
KANTERS, JØRGEN;
TOREKOV, SIGNE S.
Description:
<jats:p>Background: Patients with Long-QT syndrome (LQTS) due to a loss-of-function mutation in hERG, encoding the hERG-voltage-gated potassium channel (Kv11.1), exhibit increased glucose-stimulated insulin secretion, defective glucagon secretion, and postprandial hypoglycemia. Recently, LQTS has been reported to be associated with an increased risk of type 2 diabetes. We aimed to investigate the effect of drug-induced (moxifloxacin) blockade of the hERG-channel on glucose homeostasis.</jats:p>
<jats:p>Methods: Using a double-blinded, randomized, placebo-controlled, crossover design, 40 healthy young participants underwent two 6-hours oral glucose tolerance tests (OGTT). The intervention was a 4-day treatment period with a selective hERG-blocker (the antibiotic moxifloxacin 800 mg/day) or placebo, final dose two hours before the OGTT, separated by a 3-week washout period.</jats:p>
<jats:p>Results: Moxifloxacin prolonged the QTc interval by 25 ms. Figure 1 shows the means and 95% CI from the moxifloxacin/placebo 6-hour OGTTs. Insulin and GLP-1 levels were reduced the first 90 min and glucose was reduced the first 15 min with moxifloxacin blockade, thereby increasing the Matsuda-index by 1.16 (95% CI -1.9;-0.4).</jats:p>
<jats:p>Conclusion: Moxifloxacin-induced hERG blockade reduced peak postprandial glucose excursions and decreased the secretion of insulin and GLP-1.</jats:p>
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<jats:title>Disclosure</jats:title>
<jats:p>C.R. Juhl: None. J. Burgdorf: None. C. Knudsen: None. S. Veedfald: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. J. Kanters: None. S.S. Torekov: Research Support; Self; Novo Nordisk Inc.</jats:p>
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<jats:title>Funding</jats:title>
<jats:p>Independent Research Fund Denmark; Danish Heart Association; Lundbeck Foundation</jats:p>
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