Dietary regulation of intestinal nutrient carriers

It is well established that certain intestinal nutrient
carriers, including those transporting a number of
sugars and amino acids, are adaptively regulated by
their substrates. This type of regulation is transient
and reversible. For example, the rate (Vmax) of active
glucose uptake doubles within 12 hours when mice
fed a carbohydrate-free diet are switched to a highcarbohydrate
diet (Diamond & Karasov, 1984). If the
same mice were switched back to the carbohydratefree
diet, it would take up to 3 days for the glucose
uptake to revert to the original rate. The sole mechanism
responsible for these changes is a corresponding
increase or decrease in the number of carriers at both
the apical and basolateral membranes of the enterocytes.
There is no effect on numerous variables of
intestinal structure, such as length, circumference,
weight, villus dimensions and density, and area at the
villus level. The signal for regulation of brush-border
glucose transport is the luminal concentration of sugars
– not only glucose itself, but also nontransporting
sugars. The signal for the basolateral glucose transport
is yet to be established, but it involves signals from the
plasma. The signals are perceived in the intestinal
crypts, where the carrier proteins are synthesized
within the developing enterocytes. The observed lag
in response is attributed to the time taken for the cells
to migrate from crypt to villus.
According to the adaptive regulation/modulation
hypothesis (Karasov, 1992), a carrier should be repressed
when its biosynthetic and maintenance costs
exceed the benefi ts it provides. The benefi ts can be
provision of either metabolizable calories or an ‘essential’
nutrient, i.e. a nutrient such as an essential
amino acid which cannot be synthesized in the body
and must be obtained from the diet. Glucose carriers
are up-regulated when the dietary supply of glucose
is adequate or high because glucose provides valuable
calories. The down-regulation of glucose carriers
during a defi ciency of glucose can be explained by the
biosynthesis and maintenance costs outweighing the
benefi ts of transporting this ‘nonessential’ nutrient.
One might expect carriers for water-soluble vitamins
to be down-regulated by their substrates and upregulated
in defi ciency of the vitamins. The rationale
in this case is that carriers for these essential nutrients
are most needed at low dietary substrate levels; at high
levels the required amount of the vitamin could be extracted
from the lumen by fewer carriers or even cross
the enterocyte by simple diffusion. As vitamins do not
provide metabolizable energy, there is nothing to gain
from the cost of synthesizing and maintaining carriers
when the vitamin supply is adequate or in excess.
The prediction of suppressed transport of vitamins
at high dietary intakes has proved to be true for ascorbic
acid, biotin and thiamin, but not for pantothenic
acid, for which carrier activity is independent of dietary
levels (Ferraris & Diamond, 1989). It appears that
intestinal carriers are regulated only if they make the
dominant contribution to uptake, as is the case for the
three regulated vitamins. It can also be reasoned that
carriers for ascorbic acid, biotin and thiamin would
need to be regulated, because nutritional defi ciencies
of these vitamins can and do occur. In contrast,
there is no need to regulate pantothenic acid carriers,
because this vitamin is found naturally in almost all
foods and cases of defi ciency are extremely rare.