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Hormonal control of ketone body metabolism in the normal and diabetic state.

1982; National Institutes of Health; Volume: 11; Issue: 2 Linguagem: Inglês

Desmond G. Johnston, K. G. M. M. Alberti,

Adipose Tissue and Metabolism

In normal man the major oxidative fuels are glucose, with its byproduct lactate, fatty acids and the ketone bodies, acetoacetate and 3-hydroxybutyrate. In the fed state catabolism is suppressed and fuel utilization will depend upon the relative proportions of fat, carbohydrate and protein consumed. Amino acids, glucose and short-chain fatty acids may all be used. In the postabsorptive and fasting states there is a more consistent pattern of fuel production and utilization. Energy stores in the average man are heavily loaded in favour of fat. Glycogen in liver amounts to only 400 to 500 kilocalories, muscle protein can yield 24000 kilocalories, although mechanisms exist to prevent this, whilst triglyceride fat can supply 135 000 kilocalories (Cahill, 1976). After an overnight fast the liver releases glucose for use mainly by obligatory glucose-using tissues such as brain, red blood cells and renal medulla. Net splanchnic glucose release amounts to 0.86 mmol/min/1.73 m 2 (220 g or 860 kilocalories over a 24-hour period), approximately 80 per cent of which derives from glycogen, the rest coming from gluconeogenesis. At the same time ketone body production, which can only occur in the liver, is 0.06 mmol/min/1.73 m 2 (Owen et al, 1980) while total fatty acid turnover is approximately 0.5 mmol/min/1.73 m 2 (calculated from Hall, Saunders and Sonksen, 1979) about one-third of which is totally oxidized, and approximately 0.13 mmol/min/1.73 m2 is taken up by liver (Owen et al, 1981). After a three-day fast the situation is reversed with glucose production falling to 0:47 mmol/min/1.73 m s, now ~11 derived from gluconeogenesis, ketone body production rising to 0.75 mmol/min/1.73 m s and fatty acid turnover increasing by 60 to 70 per cent with hepatic fatty acid extraction doubled. By this time the brain is oxidizing ketone bodies, which allows glucose utilization to fall, thereby sparing amino acids and vital tissue protein. Thus in normal man, ketone bodies serve as a minor fuel during everyday life, but as soon as fasting supervenes they become all-important as oxidative fuels, and are usable by almost every tissue. The whole process