Carbohydrate metabolism

Glucose is always present in the blood. It is not static; glucose molecules are continually being removed from the blood and replaced by new glucose molecules, so that the concentration remains relatively constant, at close to 5 mmol/l in humans (Fig. 6.1). In fact, amongst all the energy substrates circulating in the blood, the concentration of glucose is by far the most constant. One reason for this is that it is necessary to provide a constant source of energy for those tissues in which the rate of glucose utilisation is regulated primarily by the extracellular glucose concentration. For instance, we have seen that in the brain the rate of glucose utilisation is fairly constant over a range of glucose concentrations, but will decrease considerably - with adverse consequences - if the glucose concentration falls below about 3 mmol/l. Furthermore, consistently elevated concentrations of glucose in blood - above about 11 mmol/l - have harmful effects, although these may take a matter of years to develop; this topic will be considered later in the consideration of diabetes mellitus (Chapter 10).

Fig. 6.1 Relative constancy of blood glucose concentrations during a typical day, compared with the relative variability of plasma insulin concentrations. For a mechanical analogy, see Fig. 6.2. Based on Reaven etal. (1988). Copyright © 1988 American Diabetes Association. From Diabetes, Vol. 37, 1988; 1020-1024. With permission of the American Diabetes Association.

Fig. 6.1 Relative constancy of blood glucose concentrations during a typical day, compared with the relative variability of plasma insulin concentrations. For a mechanical analogy, see Fig. 6.2. Based on Reaven etal. (1988). Copyright © 1988 American Diabetes Association. From Diabetes, Vol. 37, 1988; 1020-1024. With permission of the American Diabetes Association.

Glucose enters the bloodstream in three major ways: by absorption from the intestine, from the breakdown of glycogen in the liver and from gluco-neogenesis in the liver. (Remember that muscle glycogen breakdown does not liberate glucose into the blood, since muscle lacks glucose-6-phosphatase.) The relative importance of these routes will differ according to the nutritional state. Glucose leaves the blood by uptake into tissues. In normal life very little escapes into the urine; although glucose is filtered at the glomerulus, it is virtually completely reabsorbed from the proximal tubules (see Section 4.6.2).

During a typical day the average person on a Western diet eats about 300 g of carbohydrate (see Table 3.1). We can look at this in relation to the amount of free glucose in the body at any one time. The volume of blood is about 5 litres and the glucose concentration about 5 mmol/l, so the amount of glucose in the blood is about 5 x 5 = 25 mmol or (x 180, the M r [relative molecular mass]) 4.5 g. More correctly, we should look at the amount of glucose in all the extracellular fluid (about 20% of body weight - say 13 litres), i.e. about 12 g. Thus, in 24 hours, we eat enough to replace our 'glucose in solution' about 25 times. This illustrates the need for coordinated control; even a single meal (say 100 g carbohydrate) could elevate the glucose concentration about 8-fold if there were not mechanisms both to inhibit the body's own glucose production, and to increase the uptake of glucose into tissues.

The constancy of blood glucose concentration is brought about by coordinated control of various aspects of glucose metabolism. It will already be clear that insulin plays a major role in this coordination. The relationship between blood glucose and insulin concentrations is illustrated in Fig. 6.1, which shows the relative constancy of glucose compared with the variability of insulin. This is typical of many systems in which one component is varying in order to keep another constant. A useful analogy is with a thermostatically controlled water tank. At its simplest, a thermostat dips into the water. When the water temperature falls below a certain limit - for instance, 2° below the desired temperature or 'set-point' - an electrical switch is triggered and the heating element is switched on. When the temperature reaches an upper limit - perhaps 2° above the set-point - the switch cuts out. The water temperature (the controlled variable) stays constant within quite narrow limits (4° in this case), whereas the electrical current through the switch and heater (the controlling variable) varies between wide extremes (Fig. 6.2). We will reconsider, and improve upon, this analogy at the end of this chapter.

6.1.1 The postabsorptive state

The phrase postabsorptive state implies that all of the last meal has been absorbed from the intestinal tract, but not much further time has elapsed or the beginnings of starvation would be apparent. In humans, it is typically represented by the state after an overnight fast before breakfast is consumed.

In the postabsorptive state the blood glucose concentration is usually a little under 5 mmol/l. The concentration of insulin in plasma varies widely between individuals, but is typically around 60 pmol/l. The concentration of glucagon will be about 20 -25 pmol/l. (There are difficulties in giving typical glucagon concentrations. Firstly, the methods used to measure it in different laboratories tend to give varying results. Secondly, the point has already been made that glucagon exerts its metabolic effects mainly, if not entirely, in the liver, and the relevant concentration is that in the hepatic portal vein; this is not easy to measure in normal volunteers.)

The rate of turnover of glucose in the postabsorptive state is close to 2 mg of glucose per kg body weight per minute, or 130 mg glucose per minute entering

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