Normal Glucose Homeostasis

Arterial plasma glucose values throughout a 24-h period average approximately 90 mg/dl, with a maximal concentration usually not exceeding 165 mg/dl such as after meal ingestion1 and remaining above 55 mg/dl such as after exercise2 or a moderate fast (60 h).3 This relative stability contrasts with the situation for other substrates such as glycerol, lactate, free fatty acids, and ketone bodies whose fluctuations are much wider (Table 2.1).4 This narrow range defining normoglycemia is maintained through an intricate regulatory and counterregulatory neuro-hormonal system: A decrement in plasma glucose as little as 20 mg/dl (from 90 to 70 mg/dl) will suppress the release of insulin and will decrease glucose uptake in certain areas in the brain (e.g., hypothalamus where glucose sensors are located); this will activate the sympathetic nervous system and trigger the release of counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone).5 All these changes will increase glucose release into plasma and decrease its removal so as to restore normoglycemia. On the other hand, a 10 mg/dl increment in plasma glucose will stimulate insulin release and suppress glucagon secretion to prevent further increments and restore normoglycemia. Glucose in plasma either comes from dietary sources or is either the result of the breakdown of glycogen in liver (glycogenolysis) or the formation of glucose in liver and kidney from other carbons compounds (precursors) such as lactate, pyruvate, amino acids, and glycerol (gluconeogenesis). In humans, glucose removed from plasma may have different fates in different tissues and under different conditions (e.g., postabsorptive vs. postprandial), but the pathways for its disposal are relatively limited. It (1) may be immediately stored as glycogen or (2) may undergo glycolysis, which can be non-oxidative producing pyruvate (which can be reduced to lactate or transaminated to form alanine) or oxidative through conversion to acetyl CoA which is further oxidized through the tricarboxylic acid cycle to form carbon dioxide and water. Non-oxidative glycolysis carbons undergo gluconeogenesis and the newly formed glucose is either stored as glycogen or released back into plasma (Fig. 2.1).