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REVIEW ARTICLE
Studies conducted over the last 60 years in animals and in vitro have provided considerable evidence that the mammalian kidney can make glucose and release it under various conditions. Until quite recently, however, it was generally believed that the human kidney was not an important source of glucose except during acidosis and after prolonged fasting. This review will summarize early work in animals and humans, discuss methodological problems in assessing renal glucose release in vivo, and present results of recent human studies that provide evidence that the kidney may play a significant role in carbohydrate metabolism under both physiological and pathological conditions.
Diabetes Care 24:382-391, 2001
Abbreviations: NMR, nuclear magnetic resonance.
A table elsewhere in this issue shows conventional and Systeme International (SI) units and conversion factors for many substances.
To function effectively as a source of fuel in the brain, renal medulla, and nucleated blood cells and to supplement energy provided to other tissues (e.g., muscle and splanchnic organs) by free fatty acids and amino acids, glucose is normally released into the circulation of humans who were fasted overnight (postabsorption) at a rate of 10-11 (mu)mol . kg^sup -1^ . min^sup -1^ (1). This release of glucose is the result of one of two processes: glycogenolysis and gluconeogenesis. Glycogenolysis involves the breakdown of glycogen to glucose-6-phosphate and its subsequent hydrolysis by glucose-6-phosphatase to free glucose. Gluconeogenesis involves the formation of glucose-6-phosphate from precursors such as lactate, glycerol, and amino acids with its subsequent hydrolysis by glucose-6-phosphatase to free glucose. Liver and skeletal muscle contain most of the body's glycogen stores. However, because only the liver contains glucose-6-phosphatase, the breakdown of hepatic glycogen leads to the release of glucose, whereas the breakdown of muscle glycogen leads to the release of lactate. This lactate and the lactate generated via glycolysis of glucose from plasma by blood cells, the renal medulla, and other tissues can be absorbed by gluconeogenic organs and re-formed into glucose.
Recent studies using nuclear magnetic resonance (NMR) spectroscopy of changes in hepatic glycogen content (2) indicate that in overnight-fasted normal volunteers, net hepatic glycogenolysis occurred at a rate of ~5.5 (mu)mol . kg-^sup -1^ . min ^sup -1^ and accounted for 45 +/- 6% of the...