Starvation blood glucose concentration

The role of glucagon and insulin in the regulation of glu-coneogenesis, along with other factors, is to maintain the blood glucose concentration in starvation. This is discussed in Chapter 12. 

Ketone bodies are oxidised by most aerobic tissues including skeletal muscle, heart, kidney, lung, intestine and brain. Since the last two cannot oxidise fatty acids, their ability to oxidise ketone bodies is very important, because they provide another fuel in addition to, or as an alternative to, glucose. Hence, they can be used to replace some of the glucose to maintain the blood glucose concentration (e.g. in prolonged starvation or hypoglycaemia). 

In the fed state, the only fuel used by the brain is glucose, derived from the blood. In prolonged starvation or chronic hypoglycaemia, ketone bodies are nsed which rednce the rate of utilisation of glucose by the brain bnt, even so, glucose still provides about 50% of the energy. Consequently, under all conditions, maintenance of the blood glucose concentration is essential for the function of the brain the mechanisms that are responsible for this are discnssed in Chapters 6, 12 and 16. 

Rat blood normally contains about 0.07 mM acetoacetate, 0.18 mM hydroxybutyrate, and a variable amount of acetone. These amounts increase to 0.5 mM acetoacetate and 1.6 mM hydroxybutyrate after 48 h of starvation. On the other hand, the blood glucose concentration falls from 6 to 4 mM after 48 h starvation.61 Under these conditions acetoacetate and hydroxybutyrate are an important alternative energy source for muscle and other tissues.62 63 Acetoacetate can be thought of as a transport form of acetyl units, which can be reconverted to acetyl-CoA and oxidized in the citric acid cycle. 

EXAMPLE 13.4 The concentration of any metabolite in a cell is the result of the balance between its synthesis and its degradation. For cAMP, the activity of adenylate cyclase determines its rate of production whereas the activity of phosphodiesterase determines its rate of breakdown. If the activity of adenylate cyclase is greater than the activity of phosphodiesterase, then the concentration of cAMP will rise. Insulin is a potent stimulator of phosphodiesterase so that, in the fed state, the cAMP concentration in adipocytes is kept low. During starvation when insulin concentrations decrease, phosphodiesterase will not be activated. Therefore, even if adenylate cyclase is not stimulated, the cAMP concentration still rises in the absence of insulin. This outcome becomes important in diabetes when, even in the presence of high blood glucose concentrations, the lack of insulin leads to uncontrolled lipolysis from white adipose tissue. 

The utilization of ketone bodies by the brain is not limited to the neonatal period Smith et reported a six-fold increase of the activity of 3-hydroxybutyrate dehydrogenase in rat brain in starvation. Unlike the hyperketonaemia of starvation, the hyper-ketonaemia of suckling is accompanied by normal blood glucose concentrations and it is thus possible that in the brain the ketone bodies serve another function (i.e. myeliniza-tion) apart from serving as a fuel for respiration and the sparing of glucose. 

Figure 16.2 Redprocal relationship between the changes in the concentrations of glucose and fatty adds in blood during starvation in adult humans. As the glucose concentration decreases, fatty acids are released from adipose tissue (for mechanisms see Figure 16.4). The dotted line is an estimate of what would occur if fatty acid oxidation did not inhibit glucose utilisation. Such a decrease occurs if fatty acid oxidation in muscle is decreased by specific inhibitors.

For some cell lines, the glucose concentration needs to be monitored, since glucose starvation can occur The use of blood glucose strips is very effective. A drop of spent medium after a reservoir has been changed or a drop of harvested supernatant is placed on the reaction site of the strip, and left for 1 mm This is wiped off, and after a further minute, the color change is compared with a reference chart... 

When the blood glucose level falls and the liver s glycogen reserves are also exhausted, the liver still has the capacity to synthesize glucose via gluconeogenesis from amino acids that are supplied from protein breakdown. Under starvation conditions the liver forms increasing amounts of ketone bodies (see fig. 18.7). This is due to elevated concentrations of acetyl-CoA, which favor the formation of ketone bodies. The ketone bodies are secreted and used as a source of energy by other tissues, especially those tissues like the brain that cannot catabolize fatty acids directly. 

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