Potential Mechanisms Underlying Hypoxia-Induced Diabetes in a Rodent Model: Implications for COVID-19

Eung-Kwon Pae; Ronald M Harper

doi:10.3390/children8121178

Potential Mechanisms Underlying Hypoxia-Induced Diabetes in a Rodent Model: Implications for COVID-19

Children (Basel). 2021 Dec 14;8(12):1178. doi: 10.3390/children8121178.

Authors

Eung-Kwon Pae¹, Ronald M Harper²

Affiliations

¹ School of Dentistry, University of Maryland, 650 W. Baltimore St., Baltimore, MD 21201, USA.
² Department of Neurobiology, University of California at Los Angeles, Los Angeles, CA 90095, USA.

Abstract

Previous studies reported that repetitive hypoxia in rat pups reduces insulin secretion and elevates fasting blood glucose levels; these sequelae persisted for several months. This report describes how episodic hypoxic events elevate a chloride ion exporter, K⁺-Cl^- cotransporter-2 (KCC2), in the plasma membrane of insulin-secreting pancreatic β-cells. We assume that acute diabetic symptoms observed in rat pups with periodic oxygen desaturation could result from a lack of blood insulin levels due to disturbed β-cell function. This acute hypo-insulinemia may result from a disruption in chloride balance in β-cells arising from an imbalanced KCC2-NKCC1 (chloride exporter-importer) density as a consequence of periodic oxygen desaturation. Mechanistically, we postulate that a reduced insulin secretion due to the KCC2-NKCC1 imbalance subsequent to acute oxygen desaturation could result in hyperglycemia in rat pups, paralleling symptoms shown in patients with COVID-19 who experienced acute respiratory distress.

Keywords: COVID19-induced hypoxia; KCC2; chloride levels; insulin; β-cell.