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Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus

Philip E Cryer, MD
Section Editor
David M Nathan, MD
Deputy Editor
Jean E Mulder, MD


The brain relies almost exclusively on glucose as a fuel, but cannot synthesize or store much of it. As a result, adequate uptake of glucose from the plasma is essential for normal brain function and survival. Given the survival value of maintenance of the plasma glucose concentration, it is not surprising that very effective physiological and behavioral mechanisms that normally prevent or rapidly correct hypoglycemia have evolved. As a result, hypoglycemia is an uncommon clinical event except in patients who use drugs that lower glucose levels, particularly those with diabetes who use insulin, a sulfonylurea, or a glinide. In addition to being at increased risk for hypoglycemia, diabetic patients treated with insulin often have impaired neurohumoral responses to and few early symptoms of low blood glucose concentrations [1-4].

This topic card will review glucose metabolism and the response to hypoglycemia in normal subjects and in patients with diabetes. The therapeutic approach to hypoglycemia in diabetic patients is discussed separately. (See "Management of hypoglycemia during treatment of diabetes mellitus".)


In normal subjects, the extracellular supply of glucose is carefully regulated primarily by insulin and glucagon (figure 1) [1-4]. As plasma glucose concentrations rise after a meal, glucose enters the pancreatic beta-cells. In the cells, the enzyme glucokinase, which phosphorylates glucose to glucose-6-phosphate, may act as the glucose sensor, initiating a sequence of events leading to entry of calcium and insulin release. (See "Pancreatic beta cell function".)

Insulin acts to restore normoglycemia primarily through the following two mechanisms:

It decreases hepatic glucose production by diminishing both glycogenolysis and gluconeogenesis. It does so directly and indirectly by diminishing delivery of the gluconeogenic precursors, lactate and alanine, among other amino acids, and glycerol to the liver via its antiglycolytic, antiproteolytic, and antilipolytic actions.

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Literature review current through: Nov 2017. | This topic last updated: Aug 02, 2016.
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