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J M Diamond

Publications and source records attributed to J M Diamond.

At least 73 records · Page 4Linked to original sources
PubMed1987

Comparison of different dietary amino acids as inducers of intestinal amino acid transport.

Intestinal amino acid (AA) transporters are known to be induced by raised levels of dietary protein or free AA mixtures, but little is known about whether certain AAs are more potent inducers than others. Hence we compared, in mouse jejunum, the inductive effects of seven different AAs (given to mice as dietary supplements) on the brush-border uptake of five solutes predominantly taken up via different transporters. The AAs tested as dietary supplements included one imino acid, two acidic AAs, two basic AAs, and two neutral AAs. The solutes whose uptakes we studied were D-glucose plus preferential substrates for the acidic AA, basic AA, neutral AA, and imino acid transporter. Mouse growth rates were consistently higher for dietary supplementation with nonessential than essential AAs, but there were no ration-related differences in intestinal morphometric parameters and almost none in active D-glucose uptake. AA transport is regulated independently of D-glucose transport. The four AA transporters are regulated semi-independently on each other: e.g., aspartate is a good inducer for only two of the four transporters, arginine for one or two, lysine for just one. Different AAs differ in their potencies at inducing the same AA transporter. In a few cases good substrates make good inducers (e.g., aspartate of the acidic AA transporter, valine of the neutral AA transporter). But often this is not true: the acidic AA aspartate is the best inducer of the basic AA transporter; the basic AA arginine but not lysine is a good inducer of the acidic AA transporter; and the imino acid proline is not a good inducer of the imino acid transporter. The adaptive significance of these discrepancies between inducers and transported substrates is unclear. Thus the differing dietary values of different AAs may be related to their differing values as inducers of AA transport, in addition to their well-known differing biosynthetic values as essential or nonessential nutrients.

Amino Acids↗
PubMed1986

How do food passage rate and assimilation differ between herbivorous lizards and nonruminant mammals?

What digestive adaptations permit herbivorous nonruminant mammals to sustain much higher metabolic rates than herbivorous lizards, despite gross similarity in digestive anatomy and physiology? We approached this question by comparing four herbivorous species eating the same diet of alfalfa pellets: two lizards (chuckwalla and desert iugana) and two mammals (desert woodrat and laboratory mouse). The mammals had longer small and large intestines, greater intestinal surface area, much higher (by an order of magnitude) food intake normalized to metabolic live mass, and much faster food passage times (a few hours instead of a few days). Among both reptiles and mammals, passage times increase with body size and are longer for herbivores than for carnivores. The herbivorous lizards, despite these much slower passage times, had slightly lower apparent digestive efficiencies than the mammals. At least for chuckwallas, this difference from mammals was not due to differences in body temperature regime. Comparisons of chuckwallas and woodrats in their assimilation of various dietary components showed that the woodrat's main advantage lay in greater assimilation of the dietary fiber fraction. Woodrats achieved greater fiber digestion despite shorter residence time, but possibly because of a larger fermentation chamber, coprophagy, and/or different conditions for microbial fermentation. We conclude with a comparative overview of digestive function in herbivorous lizards and mammals, and with a list of four major unsolved questions.

Adaptation, Biological↗
PubMed1986

A method for measuring apical glucose transporter site density in intact intestinal mucosa by means of phlorizin binding.

Phlorizin binding has been widely used to estimate the site density of glucose transporters on intestinal and renal brush-border vesicles. Glucose transport measurements in the intact intestinal mucosa show that changes in transport rate postulated to arise from changes in site density occur under many physiological and pathological conditions. Exploring the basis of these regulatory phenomena would be facilitated by comparing changes in transport rate and site density measured in the same preparation. Hence we developed methods for measuring phlorizin binding in everted sleeves of intact mouse intestine. Specific binding of phlorizin to glucose carriers reached an asymptotic value within 120 sec, while nonspecific binding continued to rise thereafter. Hence we used 120-sec incubations. The rate of dissociation of specifically bound phlorizin was accelerated by Na+-free solutions and even more by 50 mM glucose, while the rate of dissociation of nonspecifically bound phlorizin was independent of these solution changes. Hence we chose a 20-sec rinse in Ringer + 50 mM mannitol, because it washes out 30-40% of the nonspecifically bound phlorizin but virtually none of the specifically bound phlorizin. Ligand-binding analysis of specific binding against phlorizin concentration suggested two classes of binding sites, of which the one with stronger affinity for phlorizin probably has the higher capacity for glucose transport in mouse jejunum. The calculated affinity and capacity of this component are independent of whether one estimates the specific component of total binding by adding glucose or by removing Na+.

Animals↗
PubMed1986

Use of phlorizin binding to demonstrate induction of intestinal glucose transporters.

We used specific binding of phlorizin to the intact intestinal mucosa in order to measure glucose transport site density in intestines of mice fed a high-carbohydrate or no-carbohydrate diet. Nonspecific binding varied with intestinal position but showed only modest dependence on diet. Specific binding to glucose transporters was 1.9 times greater in jejunum of high-carbohydrate mice than of no-carbohydrate mice; this ratio was the same as the ratio for Vmax values of active D-glucose uptake between the two diet groups. The gradient in specific binding of phlorizin along the intestine paralleled the gradient in Vmax of glucose transport. These results directly demonstrate that the increase in intestinal glucose transport caused by a high-carbohydrate diet is due to induction of glucose transporters. They also indicate that the normal positional gradient in glucose transport along the intestine arises from a gradient in transporters, induced by the normal gradient in luminal glucose concentration.

Animals↗
PubMed1986

A case of neuroleptic malignant syndrome in a mentally retarded adolescent.

The neuroleptic malignant syndrome is an uncommon but occasionally fatal reaction to antipsychotic medication characterized by fever, movement disorder, and stupor. A case is reported of a 16-year-old retarded male who progressed into coma after an injection of fluphenazine. The syndrome is discussed, and new pharmacological treatment approaches are reviewed. Brain-damaged patients are thought to be more susceptible to this syndrome. As recognition of the syndrome grows, there may well be more cases identified in the mentally retarded population.

Adolescent↗
PubMed1986

Aristotle revisited: the function of pyloric caeca in fish.

The function of the pyloric caeca of fish has been uncertain since their detailed description in 345 B.C. by Aristotle. He suggested three hypotheses about their function: "to store up the food," "putrify it up," and "concoct it" (i.e., storage, fermentation, and digestion). Our results for trout, cod, largemouth bass, and striped bass support the third but not the first or second of Aristotle's theories. In all four species, the caeca prove to be a major site of sugar, amino acid, and dipeptide uptake, contributing more uptake than the entire remaining alimentary tract in trout and cod. Caecal brush-border membranes contain hydrolytic enzymes. X-ray plates taken at various times after trout had ingested radioopaque marker, and observations of trout fed blue dye plus glass beads of graded sizes, show that caeca fill and empty of food with the same time course as proximal intestine. Thus, whereas the caeca of mammals and birds serve as fermentation chambers, fish caeca are an adaptation to increase gut surface area.

Animals↗
PubMed1985

Digestive adaptations for fueling the cost of endothermy.

Little is known about the digestive adaptations that enable mammals to sustain metabolic rates an order of magnitude higher than those of reptiles. Comparison of several features of digestion in mammals and lizards of similar size eating the same diet revealed that mammals processed food ten times faster and with the same or greater extraction efficiency. Transport kinetics and rates of nutrient absorption normalized to the quantity of intestinal tissue were similar in these two classes of vertebrates. The main basis for faster absorption in mammals is their much greater intestinal surface area.

Animals↗
PubMed1985

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.

Amino Acids↗
PubMed1985

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.

Amino Acids↗
PubMed1985

Crystal accumulation and very high short-circuit currents in rabbit urinary bladder.

We describe a condition in rabbits characterized by CaCO3 crystal accumulation and very high short-circuit current (Isc) in the urinary bladder. The incidence of the condition was high in rabbits kept for 2 mo or more in the vivarium. The crystal mass in the bladder increased with age or time until it occupied up to one-third of the bladder volume and occasionally aggregated as stones, and the urine attained a sludgy consistency. In animals with sludgy urine, the urine excreted had a crystal content 20 times lower than that of urine contained in the bladder at time of death, implying retention of crystals in the bladder. Kidney stones were not detected in rabbits with bladder crystals, and bladder crystals were absent in rabbits with kidney stones induced experimentally by uremia. In old rabbits with sludgy urine the Isc, a measure of Na+ transport, was up to 46 microA/cm2 and averaged 12 microA/cm2, seven times the Isc of rabbits with nonsludgy urine. The increased Isc was entirely amiloride sensitive. Noise analysis showed it to arise entirely from increased channel density, without change in single-channel current. With one possible exception, we could not find bacterial infection or abnormalities in plasma aldosterone, GFR, or urinary [Na+], [Ca2+], pH, or osmolality that could explain the condition. The exception is that some unidentified component accounting for half the osmolality of nonsludgy urine is absent or at low concentration in sludgy urine. It remains unknown why the condition develops and whether CaCO3 crystals cause high Isc or vice versa or whether both result from a third factor.

Amiloride↗
PubMed1984

Studies of sodium channels in rabbit urinary bladder by noise analysis.

Sodium channels in rabbit urinary bladder were studied by noise analysis. There are two components of short-circuit current (Isc) and correspondingly two components of apical Na+ entry, one amiloride-sensitive (termed IA and the A channel, respectively) and one amiloride-insensitive (IL and the leak pathway, respectively). The leak pathway gives rise to l/f noise, while the A channel in the presence of amiloride gives rise to Lorentzian noise. A two-state model of the A channel accounts well for how the corner frequency and plateau value of Lorentzian noise vary with amiloride concentration. The single-channel current is 0.64 pA, and the conducting channel density is on the order of 40 copies per cell. Triamterene blocks the A channel alone, and increasing external Na+ decreases the number but not the single-channel permeability of the A channel. Hydrostatic pressure pulses ("punching") increase the number of both pathways. Repeated washing of the mucosal surface removes most of the leak pathway without affecting the A channel. Properties of the A channel revealed by noise analysis of various tight epithelia are compared, and the mechanism of l/f noise is discussed. It is suggested that the A channel is synthesized intracellularly, stored in intracellular vesicles, transferred with or from vesicular membrane into apical membrane under the action of microfilaments, and degraded into the leak pathway, which is washed out into urine or destroyed. The A channel starts with PNa/PK approximately 30 and loses selectivity in stages until PNa/PK reaches the free-solution mobility ratio (approximately 0.7) for the leak pathway. This turnover cycle functions as a mechanism of repair and regulation for Na+ channels, analogous to the repair and regulation of most intracellular proteins by turnover. Vesicular delivery of membrane channels may be operating in several other epithelia.

Amiloride↗
PubMed1984

Lithium concentration in the muscle compartment of manic-depressive patients during lithium therapy.

Pharmacokinetic (PK) techniques were used to study the effect of lithium (Li+) on Li+ fluxes and concentrations in body compartments of manic-depressives. Patients not yet on Li+ therapy were similar to normal controls in all parameters. Comparison of patients before and during chronic Li+ therapy showed no effect of Li+ therapy on intestinal absorption and renal excretion of Li+. The calculated erythrocyte (RBC)-to-plasma Li+ concentration ratio increased with Li+ therapy, as already known from direct measurements. The calculated muscle-to-plasma Li+ concentration ratio was 6-8 times higher than the RBC ratio, and increased from 1.8 to 4.2 with Li+ therapy. The higher Li+ concentration in human muscle compared to RBC is attributed to muscle's higher inside-negative resting potential, and may underlie side effects that arise in muscle from Li+ therapy. The discrepancy between the observed muscle-to-plasma ratio and that predicted for a passively distributed ion is attributed to extrusion by a countertransport process, and the increase in the observed ratio with Li+ therapy is attributed to inhibition of countertransport, as already established for RBC. Since muscle resembles nerve as an excitable cell, muscle Li+ warrants evaluation as a predictor of therapeutic response and side effects during Li+ therapy.

Bipolar Disorder↗
PubMed1984

Effect of dietary carbohydrate on monosaccharide uptake by mouse small intestine in vitro.

Using intestinal sleeves in vitro, we studied the effect of dietary carbohydrate on active monosaccharide uptake in mice. Dietary carbohydrate did not affect numerous parameters of intestinal structure, such as length, circumference, weight, protein content, villus dimensions and density, and area at the villus level. Mice on a carbohydrate-free diet had active D-glucose uptake relatively independent of position along the small intestine. A carbohydrate-containing diet reversibly and within 1 day stimulated uptake except in the ileum, restoring the proximal-to-distal gradient in glucose uptake normally observed. This stimulation involved a 81-116% increase in the Michaelis- Menton constant Vmax, and also an apparent increase in the Michaelis- Menton constant Km, that may however be an artifact arising from unstirred-layer effects. Active uptake of 3-O-methyl-D-glucose also increased, permeability to glucose remained unchanged, and proline uptake reversibly decreased (probably due to the lower protein content of the carbohydrate-containing diets). The effect of fasting on active monosaccharide uptake seemed largely due to withdrawal of dietary carbohydrate, rather than of calories per se. It is concluded that dietary carbohydrate causes induction of monosaccharide carriers in the intestine, along with its more familiar induction of pancreatic amylase and intestinal disaccharidases. Substrate-dependent carrier induction may be physiologically significant in maintaining the proximal-to-distal gradient of glucose transport. An appendix presents measurements of villus area as a function of position along the intestine.

3-O-Methylglucose↗
PubMed1983

Turnover, membrane insertion, and degradation of sodium channels in rabbit urinary bladder.

Noise analysis of rabbit bladder revealed two components: Lorentzian noise, arising from interaction of amiloride with the Na+ channel, and flicker noise (l/f, where f is frequency), as in other biological membranes. Hydrostatic pressure, which causes exchange between intracellular vesicular membrane and apical membrane, increases the number but not the single-channel current of the amiloride-sensitive channels. Flicker noise arises from degraded channels that have lost amiloride sensitivity and Na+ to K+ selectivity. The degraded channels were selectively removed by washing the mucosal surface. These results imply channel turnover by intracellular synthesis, transfer from vesicular to apical membrane, degradation, and elimination.

Amiloride↗