Dependence of intestinal amino acid uptake on dietary protein or amino acid levels.

To understand how intestinal amino acid (AA) transport is regulated by dietary substrate levels, we measured uptake of seven AAs and glucose across the jejunal brush-border membrane of mice kept on one of three isocaloric rations differing in nitrogen content. In the high-protein ration, uptake increased by 77-81% for the nonessential, less toxic AAs, proline, and aspartate but only by 32-61% for the more toxic essential AAs tested. In the nitrogen-deficient ration, uptake decreased for the nonessential aspartate and proline but stayed constant or increased for essential AAs and for the nonessential alanine. These patterns imply independent regulation of the intestine's various AA transporters. With decreasing dietary AA (or protein), the imino acid and acidic AA "private" transporters are repressed, while activities of the basic AA transporter and the neutral AA "public" transporter decrease to an asymptote or else go through a minimum. These regulatory patterns can be understood as a compromise among conflicting constraints imposed by protein's multiple roles as a source of calories, nitrogen, and essential AAs and by the toxicity of essential AAs at high concentrations.

Comparison of different dietary sugars as inducers of intestinal sugar transporters.

Intestinal sugar transport increases with dietary carbohydrate levels, but the specific regulatory signals involved have been little studied. Hence we compared rations containing one of five sugars [D-glucose, D-galactose, 3-O-methyl-D-glucose (3-O-MG), D-fructose, and maltose] in their effects on brush-border uptake of five transported solutes (D-glucose, D-galactose, 3-O-MG, D-fructose, and L-proline) by everted sleeves of mouse small intestine. As confirmed by transepithelial potential difference (PD) measurements, there is a distinct fructose transporter that does not evoke a PD, along with one or more aldohexose transporters that do evoke a PD. Galactose and 3-O-MG rations cause a twofold increase in feeding rates, mucosal hyperplasia, and hence nonspecific increases in uptake per unit length of intestine for all transported solutes. Dietary fructose is by far the best specific inducer of the fructose transporter. The five dietary sugars are of fairly similar potency as specific inducers of aldohexose transport, but dietary galactose and fructose may be slightly more potent than glucose. Regulatory signals need not be transported substrates, or vice versa, and need not be metabolizable. Variation in uptake ratios of pairs of aldohexoses with ration and intestinal position suggest multiple aldohexose transporters of overlapping specificity, with different relative activities at different positions and with different susceptibilities to induction by different dietary sugars.

Is intestinal transport of sugars and amino acids subject to critical-period programming?

Physiological responses include three sorts: reversible within an individual's lifetime, fixed irreversibly at some critical period in life, and genetic. Examples of the first and third but not the second sort have been demonstrated for intestinal nutrient transport. Hence, we searched for critical-period programming of sugar and amino acid transport by mouse small intestine. Mice were maintained on either of two rations from gestation through birth, lactation, and weaning until adulthood: a high-carbohydrate, maintenance-protein ration and a carbohydrate-free, high-protein ration. The two groups of mice were then compared in adulthood while both groups were on the former or the latter ration. Early diet has irreversible effects on gut and body size; because of higher growth rates until weaning mice receiving high-carbohydrate diets achieved and maintained higher weights, longer guts, and heavier proximal guts than the mice receiving carbohydrate free diets. This difference increased with litter size and may have arisen from limitations on nursing mothers' ability to convert dietary protein into milk carbohydrate or fat. Early diet appears to exert some general effects on adult intestinal transport as a result of these differences in body and gut size but does not appear to exert specific irreversible effects on transport of D-glucose, L-proline, L-leucine, L-lysine, or L-aspartate or on passive glucose permeability. Active and passive glucose transport increases reversibly on a high-carbohydrate diet, whereas amino acid transport increases reversibly on a high-protein diet.

What transport adaptations enable mammals to absorb sugars and amino acids faster than reptiles?

What digestive adaptations enable mammals to process much more food in much less time with equal or higher digestive efficiency than reptiles and thus to sustain much higher metabolic rates? To answer this question, we measured glucose and proline uptake in small intestinal sleeves of three mammal and three reptile species of similar body size and natural diet. All species exhibit saturable, stereospecific uptake of D-glucose and Na+-dependent L-proline uptake. Passive permeability to glucose is high in hamsters and low in the other species. Uptake increases with temperature up to a maximum around 45-50 degrees C. This temperature dependence may help explain why reptiles bask after meals and why their digestion is impaired if basking is prevented. The total uptake capacity of the small intestine for glucose and proline is seven times higher in mammals than similar-sized reptiles, mainly because the area of mammalian intestine is 4-5.5 times greater. Minor reasons for the higher uptake capacity of mammals are that the transport activity of mammal intestine normalized to quantity of tissue is up to twofold higher and that reptile intestine operates at a lower temperature at night. Vmax for glucose transport varies 10-fold among species, but apparent differences in Km values may be unstirred-layer artifacts. Carrier-mediated uptake of glucose and proline is measurable in the colon of at least three species, but the uptake capacity of the colon is less than 10% of that of the small intestine. An appendix presents a method for measuring the microscopic area of intestines with ridges rather than villi, applies this method to desert iguana intestine, and measures area amplification due to villi in wood rat intestine.

Regulation of proline and glucose transport in mouse intestine by dietary substrate levels.

Active uptake of D-glucose and L-proline at 50 mM was measured in everted intestinal sleeves of mice whose dietary carbohydrate and protein levels were being varied experimentally. Compared to a nearly carbohydrate-free meat diet, a 50% carbohydrate laboratory chow diet stimulated active glucose uptake in the proximal intestine without affecting proline uptake, passive glucose permeability, or several measures of mucosal mass. Switching from a low-protein high-carbohydrate to a high-protein no-carbohydrate diet reversibly stimulated proline uptake while inhibiting glucose uptake. For each solute and diet switch, the stimulation of transport was complete within 1 day, while the inhibition required several days. The results imply induction and repression of intestinal glucose and proline transport by dietary substrate levels. This mechanism, in conjunction with the normal gradient of nutrient concentrations along the intestine, is probably largely responsible for the gradient in nutrient transport along the intestine.