How sweet it isn't: Repeat episodes of low blood sugar spell diabetic disaster

Low blood glucose (hypoglycemia) can occur when a person with diabetes has injected too much insulin, eaten too little food, or exercised without extra food. They may experience nausea, sweating, faintness, and confusion. In reaction to these symptoms the person is prompted to eat, and the body instinctively knows to take counterregulatory measures including decreasing insulin secretion, and increasing glucagon and epinephrine secretion. Single or repeated episodes of hypoglycemia can impair the body's ability to detect low blood sugar in the future. This impairment can allow an individual to develop severe hypoglycemia in which they may lose consciousness, experience convulsions, fall into a coma, and suffer brain damage. This failure to respond to hypoglycemia has become a major limitation to effective insulin therapy in type 1 diabetes.

In a study appearing in the June issue of the Journal of Clinical Investigation, Rory J. McCrimmon and colleagues from Yale University, show that administration to the brain of urocortin I suppresses the counterregulatory response to hypoglycemia for at least 24 hours in rats. They show that urocortin I, which activates corticotrophin-releasing factor receptor 2 (CRFR2), impairs the sensitivity of glucose-sensing neurons in the brain. In contrast, administration of CRF, which activates CRFR1, amplifies the response to hypoglycemia. The data suggest that the regulation of the counterregulatory response to hypoglycemia is largely determined by the interaction between CRFR2-mediated suppression and CRFR1-mediated activation in the hypothalamus.

In an accompanying commentary, Philip Cryer from Washington University School of Medicine discusses how hypoglycemia in diabetes will likely remain a problem until safe and effective methods are developed that would offer insulin replacement based on plasma glucose concentration.

TITLE: Corticotrophin-releasing factor receptors within the ventromedial hypothalamus regulate hypoglycemia-induced hormonal counterregulation

AUTHOR CONTACT: Rory J. McCrimmon
Yale University, New Haven, Connecticut, USA.
Phone: (203) 785-4664; Fax: (203) 737-5558; E-mail: rory.mccrimmon@yale.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=27775

ACCOMPANYING COMMENTARY

TITLE: Mechanisms of sympathoadrenal failure and hypoglycemia in diabetes

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://www.the-jci.org/article.php?id=28735

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