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J M Diamond

Publications and source records attributed to J M Diamond.

At least 55 records · Page 3Linked to original sources

Ontogenetic development of monosaccharide and amino acid transporters in rabbit intestine.

We measured brush-border uptakes of seven sugars and amino acids by rabbit intestine as a function of age from the day of birth to adulthood. Gut dimensions, especially those of the colon and cecum, increase more rapidly with body weight than would be true if rabbits maintained identical proportions as they grew. However, nominal small intestinal area increases in approximately direct proportion to the animal's basal metabolic rate. For all solutes except fructose, uptake per milligram of intestinal tissue is maximal at or near birth and declines to a level 2.5-5 times lower in the adult. Because of small intestinal growth, though, the total uptake capacity of the whole length of the small intestine increases in approximately direct proportion to metabolic rate. Fructose uptake per milligram is unique in increasing steeply at the time of weaning, correlated with the post-weaning first appearance of fructose in the natural diet. Age-related changes in uptake ratios among aldohexoses or amino acids suggest developmental sequences of related transporters. Correlated with the very high protein content of rabbit milk, the proline-to-glucose uptake ratio is higher in suckling rabbits than in other sucking mammals. Remarkably, the ratio for adult rabbits is higher than in other monogastric herbivores and is instead similar to values for carnivores. In explanation, although the transport capacity of the small intestine appears to account for proline absorption in rabbits of all ages and for sugar absorption in suckling rabbits, the hindgut may be a major site of carbohydrate digestion in adult rabbits.

Aging↗

Luminal glucose concentrations in the gut under normal conditions.

Luminal glucose (Glc) concentrations in the small intestine (SI) are widely assumed to be 50-500 mM. These values have posed problems for interpreting SI luminal osmolality and absorptive capacity, Glc transporter Michaelis-Menten constants (Km), and the physiological role of active Glc transport and its regulation. Hence we measured luminal contents, osmolality, and Glc, Na+, and K+ concentrations in normally feeding rats, rabbits, and dogs. Measured Glc concentrations were compatible with the portion of measured osmolality not accounted for by Na+ and K+ salts, amino acids, and peptides. Mean SI luminal osmolalities were less than or equal to 100 mosmol/kg hypertonic. For animals on the most nearly physiological diets, SI Glc concentrations averaged 0.4-24 mM and ranged with time and SI region from 0.2 to a maximum of 48 mM. The older published very high values are artifacts of direct infusion of concentrated Glc solutions into the gut, nonspecific Glc assays, and failure to test for quantitative recovery or to centrifuge samples in the cold. By storing food after meals and releasing it between meals, rat stomach greatly damps diurnal fluctuations in quantity and osmolality of food reaching the SI and hence also damps fluctuations in absorption rates. These new values for luminal Glc have five important physiological implications: the problem of accounting for apparently very hypertonic SI contents in the face of high osmotic water permeability disappears; the effective Km of the SI Glc transporter is now comparable to prevailing Glc concentrations; the SI no longer appears to have enormous excess absorptive capacity for Glc; regulation of Glc transport by dietary intake now makes functional sense; and the claim that high luminal Glc concentrations permit solvent drag to become the major mode of Glc absorption under normal conditions is undermined.

Animals↗

The present, past and future of human-caused extinctions.

This paper re-evaluates whether we are really at the start of a mass extinction caused by humans. I consider the present, past and future of human-caused extinctions. As regards the present, estimates of extinction rates based on Red Data Books underestimate real values by a large factor, because the books evaluate only those species that have attracted specific attention and searches. Especially in tropical areas with few resident biologists, many poorly known species go extinct without having been the object of specific attention, and others disappear even before being described. A 'green list' of species known to be secure is needed to complement 'red books' of species known to be extinct. As regards the past, it is now clear that the first arrival of humans at any oceanic island with no previous human inhabitants has always precipitated a mass extinction in the island biota. Well-known victims include New Zealand's moas, Madagascar's giant lemurs, and scores of bird species on Hawaii and other tropical Pacific islands. Late-Pleistocene or Holocene extinctions of large mammals after the first arrival of humans in North America, South America and Australia may also have been caused by humans. Hence human-caused mass extinction is not a hypothesis for the future but an event that has been underway for thousands of years. As regards the future, consideration of the main mechanisms of human-caused extinctions (overhunting, effects of introduced species, habitat destruction, and secondary ripple effects) indicates that the rate of extinction is accelerating.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Interspecific variation in sugar and amino acid transport by the avian cecum.

Previous studies of cecal sugar and amino acid transport in the domestic chicken led to a widely held generalization that the avian cecum is unimportant as a site of nutrient transport. In fact, we found that the uptake capacity of the cecum for hexose sugars and amino acids is substantial in some species of birds. Cecal transport of glucose was measurable in all five study species (Canada goose, sage grouse, domestic chicken, red-necked phalarope, and rock dove), approached or exceeded intestinal levels in the grouse and phalarope, and accounted for between 0.1% (rock dove) and 49% (sage grouse) of the whole gut's integrated uptake capacity. Proline uptake averaged higher in the proximal portion of the cecum than in any region of the small intestine for all species but the goose. The ceca contributed between 2% (rock dove) and 25% (sage grouse) of the gut's integrated uptake capacity for proline. Similar ranges were found for fructose, lysine, leucine, and aspartate. Future studies should be undertaken to search for phylogenetic and ecological correlates of the interspecific variation in cecal transport and to determine how nutrient transport integrates with other functions of the avian cecum.

Amino Acids↗

Do dietary levels of pantothenic acid regulate its intestinal uptake in mice?

While regulation of intestinal transporters is established for other nutrients, evidence concerning regulation of intestinal vitamin transport is scanty. Hence, we compared intestinal pantothenic acid (PA) uptake in mice fed diets with high, normal and deficient PA levels. PA uptake is distributed along the small intestine, Na(+)-dependent and saturable. Signs of PA deficiency were weight loss or reduced growth, then hair loss and exudation around the eyes, then diarrhea and hindleg paralysis and splenomegaly, and finally death. Treatment of mice with an antibiotic was found to be necessary to elicit severe signs of PA deficiency, probably because mice normally can obtain PA synthesized by intestinal bacteria. Dietary PA levels had no effect on intestinal PA uptake at 5 microM. A small increase in the Vmax of uptake, observed in late-stage deficiency, is probably too small to be physiologically significant. Comparison with published results for other water-soluble vitamins suggests that intestinal transporters may be regulated only for vitamins absorbed predominantly by carrier-mediated transport and subject to natural deficiency states.

Animals↗

Origin of regional and species differences in intestinal glucose uptake.

Differences in intestinal absorption among physiological states, intestinal regions, and animal species could arise from many anatomical factors (e.g., intestinal length and diameter, or area amplification by villi and microvilli) and biochemical factors (e.g., transporter density and turnover number). In no comparison had all these factors been measured. Hence we made the necessary new measurements to identify the origin of differences in glucose absorption among three species (mouse, desert wood rat, and desert iguana) and among three intestinal regions in two of these species. Turnover numbers range from 6,900 to 32,300 glucose molecules per minute per site. Microvilli amplify intestinal area by a larger factor (36-96 times) than do villi (2-14 times), so that the intestine's actual area is at least 110-1,280 times the nominal area of the equivalent smooth-bore cylinder. Species comparisons among mammals yield the striking result that the area of the whole length of the small intestine at the microvillus level varies nearly linearly as the mammal's metabolic live mass. For the species studied, all the anatomical and biochemical factors studied proved to make significant contributions to species and regional difference in glucose uptake.

Animals↗

Labeling patients.

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Borderline Personality Disorder↗

pH dependence of histidine affinity for blood-brain barrier carrier transport systems for neutral and cationic amino acids.

The effects of pH (3.5-7.5) on the brain uptake of histidine by the blood-brain barrier (BBB) carriers for neutral and cationic amino acids were tested, in competition with unlabeled histidine, arginine, or phenylalanine, with the single-pass carotid injection technique. Cationic amino acid ( [14C]arginine) uptake was increasingly inhibited by unlabeled histidine as the pH of the injection solution decreased. In contrast, the inhibitory effect of unlabeled histidine on neutral amino acid ( [14C]phenylalanine) uptake decreased with decreasing pH. Brain uptake indices with varying histidine concentrations indicated that the neutral form of histidine inhibited phenylalanine uptake whereas the cationic form competed with arginine uptake. Since phenylalanine decreased [14C]histidine uptake at all pH values whereas arginine did not, it was concluded that the cationic form of histidine had an affinity for the cationic carrier, but was not transported by it. We propose that the saturable entry of histidine into brain is, under normal physiological circumstances, mediated solely by the carrier for neutral amino acids.

Amino Acids↗

Adaptive regulation of intestinal nutrient transporters.

Because most eukaryotic somatic cells are bathed in a constant internal milieu, most of their proteins are constitutive, unlike the adaptive enzymes of bacteria. However, intestinal mucosal cells, like bacteria, face a varying milieu. Hence, we tested for adaptive regulation of intestinal nutrient transporters, sought its functional significance, and compared it with regulation of bacterial proteins. All 12 transporters studied proved to be regulated by dietary substrate levels. Regulation in the intestine is slower than in bacteria and shows lower peak-to-basal activity levels. Regulatory patterns vary greatly among transporters: two sugars and two nonessential amino acids monotonically up-regulate their transporters, two vitamins and three minerals monotonically down-regulate their transporters, and two transporters of essential amino acids respond nonmonotonically to levels of their substrates. These varied patterns arise from trade-offs among four factors: transporter costs, calories yielded by metabolizable substrates, fixed daily requirements of essential nutrients, and toxicity of certain nutrients in large amounts. Based on these trade-offs, we predict the form of regulatory pattern for intestinal transporters not yet studied.

Amino Acids↗

Pyloric ceca of fish: a "new" absorptive organ.

The functions of the blind appendages attached to the proximal intestine of many fish, the pyloric ceca, have been disputed. Hence we recorded morphological parameters and nutrient uptake rates in the ceca and intestine of four fish species (rainbow trout, cod, largemouth bass, and striped bass) with various degrees of cecal development (the ceca contribute 70, 69, 42, and 16% of the total postgastric surface area, respectively). Proline and glucose uptake, measured in vitro, is similar in the ceca and proximal intestine. For these two solutes in these four species, and for 10 other solutes (9 amino acids and 1 dipeptide) in trout, the ceca contribute about the same percentage to uptake as to total gut area. Trout ceca and intestine have similar membrane-bound disaccharidase activity. Separate experiments with trout fed either graded glass beads or a radiopaque marker and then X-rayed show that the ceca fill and empty with particles less than 150 microns and over the same time course as the proximal intestine. Thus ceca are an adaptation for increasing intestinal surface area without increasing the length or thickness of the intestine itself. Fish ceca are entirely different from the distally located ceca of birds and mammals, which have fermentation functions.

Animals↗

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.

3-O-Methylglucose↗

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.

Amino Acids↗