Treatment with insulin revolutionized the life of individuals with diabetes. However, because insulin acts to lower blood glucose levels, it can cause hypoglycemia (low levels of glucose in the blood), which, if prolonged, can lead to brain injury and coma. Although most brain defects can be corrected by restoring blood glucose levels to normal, extremely prolonged hypoglycemia can cause the death of neurons and irreversible brain damage. Surprisingly, in a study appearing in the April issue of the Journal of Clinical Investigation, researchers from the University of California at San Francisco found that in mice, hypoglycemic neuronal death is triggered when the mice are treated with a large amount of glucose and not by the hypoglycemia itself.
Raymond Swanson and colleagues showed that although hypoglycemia induced some neuronal death, the rapid infusion of glucose into hypoglycemic mice triggered more extensive neuronal death. The extent of neuronal death correlated with the production of superoxide by a molecule known as NADPH oxidase. Importantly, the amount of superoxide produced and the extent of neuronal death increased as the amount of glucose infused into the hypoglycemic mice was increased. This suggests that it might be best to treat individuals in hypoglycemic coma by gradually increasing their blood glucose levels rather than by restoring glucose levels rapidly. However, in an accompanying commentary, Philip Cryer from Washington University School of Medicine, St. Louis, cautions that "The appropriate clinical extrapolation of these data is not entirely clear."
TITLE: Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase
AUTHOR CONTACT:
Raymond A. Swanson
University of California at San Francisco and Veterans Affairs Medical Center, San Francisco, California, USA.
Phone: (415) 750-2011; Fax: (415) 750-2273; E-mail: raymond.swanson@ucsf.edu .
View the PDF of this article at: https://'.the-jci.org/article.php?id=30077
ACCOMPANYING COMMENTARY
TITLE: Hypoglycemia, functional brain failure, and brain death
AUTHOR CONTACT:
Philip E. Cryer
Washington University School of Medicine, St. Louis, Missouri, USA.
Phone: (314) 362-7635; Fax: (314) 362-7989; E-mail: pcryer@wustl.edu .
View the PDF of this article at: https://'.the-jci.org/article.php?id=31669
Journal of Clinical Investigation