section 22.5
Carbohydrate Homeostasis
503
acid synthesis. Glucocorticoids stimulate fatty acid break-
down and gluconeogenesis and increase the rate of glyco-
gen synthesis. This action appears counterproductive, but
glucocorticoids are a major signal for the degradation of
muscle proteins and thus for gluconeogenesis. Glucocor-
ticoid effects are long term (whereas those of glucagon
are short term), but they are synergistic and act through
induction of enzymes of gluconeogenesis. Regulation by
glucocorticoids may involve increases in the amounts of
regulatory proteins that are involved in the actions of
glucagon. Many allosteric regulators in addition to hor-
mones fine-tune the gluconeogenic pathway at the steps
catalyzed by pyruvate carboxylase, phosphoenolpyruvate
carboxykinase, fructose-bisphosphatase, and glucose-6-
phosphatase. A summary of glucose homeostasis during
fasting is shown in Figure 22-17.
The sources of carbon for hepatic glucose formation are
hepatic glycogen, lactate from red blood cells or skeletal
muscle, amino acids from muscle protein, and glycerol
from adipocytes. The kidney reabsorbs the glucose in the
glomerular filtrate and is a site of gluconeogenesis. In
mammals, there is no net conversion of fatty acids to glu-
cose because during oxidation of acetyl-CoA to CO
2
via
the TCA cycle there is no net production of oxaloacetate.
However, fatty acids, play an important role in glucose
homeostasis (Figure 22-17). Since brain and red blood
cells use glucose, the heart functions well on fatty acids
without depleting glucose levels. When glucose levels
are low, only tissues that have a requirement for glucose
and are insulin-independent use glucose because, with
low insulin levels, there is essentially no glucose uptake
by insulin-dependent tissues. After fasting for a 24-hour
period, 180 g of glucose is produced from glycogen or glu-
coneogenesis, of which 75% is used by the brain and the
remainder by red and white blood cells, etc. From the latter,
about 36 g of lactate return to the liver for gluconeogenesis,
H E A R T
F I G U R E 2 2 - 1 7
Glucose homeostasis in the fasting state. TG, Triacylglycerol; RBC, red
blood cells; FA, fatty acid; AA, amino acid.
