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L-type Calcium Channel Blockade Worsens Glucose Tolerance and β-Cell Function in C57BL6/J Mice Exposed to
Stanley M Chen-Cardenas1, Tess A Baker2, Larissa A Shimoda3
1Division of Endocrinology, Diabetes, and Metabolism. Johns Hopkins University School of Medicine. Baltimore, Maryland.
American Journal of Physiology. Endocrinology and Metabolism
|January 10, 2025
Summary
Intermittent hypoxemia (IH) from sleep apnea worsens glucose control. Nifedipine, a blood pressure drug, also impairs glucose metabolism, and combined, they severely disrupt insulin function and glucose tolerance.
Area of Science:
- Endocrinology
- Cardiovascular Pharmacology
- Sleep Medicine
Background:
- Obstructive sleep apnea (OSA) causes intermittent hypoxemia (IH), negatively impacting glucose homeostasis.
- Nifedipine, an L-type calcium channel blocker for hypertension, can also affect insulin sensitivity and secretion.
- The combined effects of IH and nifedipine on glucose metabolism remain uninvestigated.
Purpose of the Study:
- To investigate the cumulative and interactive effects of intermittent hypoxemia (IH) and nifedipine on glucose homeostasis in mice.
Main Methods:
- Adult male C57BL6/J mice were exposed to IH or intermittent air (IA) for five days.
- Mice received either nifedipine (20 mg/kg/day) or vehicle via osmotic pumps.
- Four groups were established: IA-vehicle, IA-nifedipine, IH-vehicle, and IH-nifedipine.
Main Results:
- IH significantly increased fasting glucose and insulin levels compared to controls.
- Nifedipine alone worsened glucose tolerance, and IH exacerbated this impairment.
- Nifedipine reduced glucose-stimulated insulin secretion and the insulinogenic index, effects further worsened by IH.
Conclusions:
- Intermittent hypoxemia detrimentally impacts insulin sensitivity and glucose tolerance.
- Nifedipine exacerbates these disturbances by impairing pancreatic beta-cell function.
- Caution is advised when prescribing L-type calcium channel blockers to OSA patients, especially those at risk for type 2 diabetes.
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