The Concept of CMR

Glucose Metabolism

Sources of glucose

Along with fatty acids, glucose is one of the body’s major energy sources. Virtually all body tissues use a mixture of glucose and fatty acids as substrates for ATP production, with some (brain, red blood cells) using glucose almost exclusively. Because the brain needs glucose continually, mammals have developed an exquisitely precise regulatory system to ensure that adequate amounts of glucose are always present within a narrow concentration range in the bloodstream.

In its free form or as part of more complex sugars, glucose is present in a wide range of foods. It is readily taken up from the gut and delivered to various tissues. Excess glucose is stored as glycogen, mainly in the liver and skeletal muscle. Some excess glucose can also be converted to fatty acids through a process called lipogenesis, mainly in the liver. The fatty acids are eventually delivered by lipoproteins to adipose tissue for long-term storage in the form of triglycerides.

Between meals, and especially at night, there is no incoming glucose from external sources, and the body must maintain blood glucose from endogenous sources. The major organ that provides glucose to the blood is the liver. A primary source of hepatic glucose is glycogen, a glucose polymer that is synthesized when plenty of glucose is available and provides a ready source of energy when necessary. In times of need, glycogen is hydrolyzed back into glucose molecules that are then exported to the bloodstream. A second important source of glucose comes from the synthesis of new glucose molecules from precursors such as glycerol (from hydrolysis of triglycerides in adipose tissue), lactate (from muscle anaerobic glycolysis), and some amino acids (from the breakdown of muscle proteins) through a process called gluconeogenesis. The latter occurs mainly in the liver, with the kidneys playing a small additional role. The rate of gluconeogenesis is driven mainly by the availability of precursors (which increase in the fasted state) and by the rate of fatty acid oxidation in the liver (also increased in the fasted state). If dietary nutrients are not incoming, the liver provides glucose to the bloodstream, ensuring a steady supply of fuel to the brain. Other tissues (e.g., muscle) also take up glucose in the fasted state but rely mainly on fatty acids (from hydrolysis of triglycerides in adipose tissue) as an energy substrate, thereby sparing glucose for use by the brain.