The chemical structure of glucose and glycogen. Glucose,
C6H12O6, is the energy source for most cells of the body. Glycogen is the
storage form of glucose. It is a highly branched chain of about a million
glucose molecules. The diagram shows just a tiny portion of a glycogen
molecule. p. 42
Blood glucose levels are maintained primarily by the
antagonistic actions of insulin and glucagon. Both hormones are secreted
by the pancreas in response to the amount of glucose in the blood.
Insulin lowers the blood glucose level, whereas glucagon raises it. p. 42
Five phases of glucose homeostasis. The graph,
based on observations of a number of individuals,
illustrates glucose utilization in a 70 kg
man who consumed 100 g of glucose and
then fasted for 40 days. The complexity of carbohydrate metabolism in mammals is evident from the
changes that occur on feeding and starvation. In the 1960s, George Cahill examined the
glucose utilization of obese patients as they underwent therapeutic starvation. After an
initial feeding of glucose, the subjects received only water, vitamins, and minerals.
Cahill noted that glucose homeostasis (maintenance of constant levels in the circulation)
proceeds through five phases. Figure 12.29, based on Cahill’s observations, summarizes
the metabolic changes in the five phases.
1. During the initial absorptive phase (the first four hours), dietary glucose enters the
liver via the portal vein and most tissues use glucose as the primary fuel. Under
these conditions, the pancreas secretes insulin, which stimulates glucose uptake by
muscle and adipose tissue via GLUT4. The glucose taken up by these tissues is
phosphorylated to glucose 6-phosphate, which cannot diffuse out of the cells. Liver
cells also absorb glucose and convert it to glucose 6-phosphate. Excess glucose is
stored as glycogen in liver and muscle cells.
2. When the dietary glucose is consumed, the body mobilizes liver glycogen to maintain
circulating glucose levels. In the liver, glucose 6-phosphatase catalyzes the hydrolysis
of glucose 6-phosphate to glucose, which exits the liver via glucose transporters.
Glycogen in muscle (which lacks glucose 6-phosphatase) is metabolized to lactate
to produce ATP for contraction; the lactate is used by other tissues as a fuel or by
the liver for gluconeogenesis.
3. After about 24 hours, liver glycogen is depleted, and the only source of circulating
glucose is gluconeogenesis in the liver, using lactate, glycerol, and alanine as precursors.
Fatty acids mobilized from adipose tissue become an alternate fuel for most
tissues. The obligatory glycolytic tissues continue to use glucose and produce lactate,
which is converted to glucose in the liver by the Cori cycle; this cycle makes
energy, not carbon, from fatty acid oxidation in the liver available to other tissues.
4. Gluconeogenesis in the liver continues at a high rate for a few days, then decreases.
As starvation progresses, gluconeogenesis in the kidney becomes proportionately
more significant. Proteins in peripheral tissues are broken down to provide gluconeogenic
precursors. In this phase, the body adapts to several alternate fuels.
5. In prolonged starvation, there is less gluconeogenesis and lipid stores are depleted.
If refeeding does not occur, death will follow. On refeeding, metabolism is quickly
restored to the conditions of the fed state. p. 380