bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of prostaglandin E2 in zinc absorption in the rat.
Authors: Song M K , Adham N F
Published: December 2017

The supernatant of cytoplasmic extract of rat small intestine was mixed with 65Zn and subjected to Sephadex G-75 column chromatography. The activity of 65Zn was detected in four peaks with estimated 800, 10,000, 50,000-75,000 mol wt, and larger than 100,000 daltons. The zinc-binding ligand from the 800 mol wt peak was prostaglandin or prostaglandin-like as indicated by ultra-violet absorption spectrum, by absorption spectrum shift in alcoholic potassium hydroxide, by its effects on pulmonary vascular resistance, and by radioimmunoassay. Addition of prostaglandin E2 or prostaglandin extracted from rat small intestine with ethyl acetate into the lumen of intestinal sacs resulted in a two to threefold increase in the activity of 65Zn in the external medium after 15-20 min incubation. The absorption and tissue distribution of orally administered 65Zn were decreased by 60% in indomethacin-treated rats and increased 70% when ethyl acetate-extracted prostaglandin and radioactive zinc were given simultaneously. These data suggest that prostaglandin not only binds zinc, but also facilitates its transport across the intestinal mucosa.
Na+ transport by mammalian stomach.
Authors: Machen T E , Silen W , Forte J G
Published: December 2017

Gastric mucosas from newborn pigs (0--20 days) and rabbits (0--20 days) were used for in vitro investigation of active Na+ transport during resting (no HCl secretion) conditions. As measured with 22Na+, these tissues actively absorb Na+ from the mucosal-to serosal (m-t-s) bathing solution during both open-circuit and short-circuit current (Is) conditions. In the nonsecreting state, net Na+ transport accounts for 40--60% of Isc. The remaining current is provided by net s-to-m flux of Cl-. Amiloride (2-5 X 10(-5) M) in the mucosal solution abolishes this active Na+ transport by inhibiting m-to-s fluxes of Na+ (JNams). In vivo-in vitro experiments showed that active Na+ transport is a normal function of the resting mammalian stomach. Decreasing pH of the mucosal solution below pH 5 reversibly causes decreased current-generating capability of the tissue. Pretreatment of the tissue with amiloride abolishes this pH effect. The implication is that the low pH affects the Na+-entry step into cells. "Titration curves" of current vs. pH had an apparent pK approximately 4.0. Ouabain and K+-free solutions both cause decreases in active Na+ and Cl- current. Calculations indicate that a shunt may account for only a small (less than 30%) percentage of total transepithelial conductance.
Norepinephrine: hormone and neurotransmitter in man.
Authors: Silverberg A B , Shah S D , Haymond M W , Cryer P E
Published: December 2017

To determine whether norepinephrine could subserve a hormonal as well as a neurotransmitter function, norepinephrine was infused for 60 min into each of five normal young men in doses of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min. After infusion, the plasma norepinephrine concentration fell with a mean (+/-SD) half-time of 2.4 +/- 0.7 min. The mean (+/-SD) norepinephrine metabolic clearance rate was 3,070 +/- 200 ml/min. The calculated basal plasma norepinephrine production rate was 0.7 microgram/min. The blood pressure and circulating glycerol, acetoacetate, beta-hydroxybutyrate, and glucose (increased) and the heart rate and circulating insulin, lactate, pyruvate, and alanine (decreased) exhibited highly significant parabolic relationships with the steady-state plasma norepinephrine concentrations. However, norepinephrine levels in excess of 1,800 pg/ml were required to produce hemodynamic and/or metabolic effects. Thus, under usual conditions, the biologic actions of norepinephrine can be attributed only to its sympathetic neurotransmitter function. Plasma norepinephrine concentrations do at times exceed 1,800 pg/ml during exercise and during major acute illness. Thus, under conditions of stress, norepinephrine may subserve a hormonal, as well as a neurotransmitter, function.
Sexual maturation of male rats in continuous light.
Authors: Piacsek B E , Statham N J , Goodspeed M P
Published: December 2017

Male rats were raised from birth in either continuous light (LL) or in 14 h light/10 h dark per day (LD) at 22 +/- 1 degree C. Food and water were administered ad libitum. Groups of rats were killed by decapitation at 14, 20, 25, 35, 41, 45, 51, 55, 58, 63, and 79 days of age. Testicular (TW), ventral prostate (VPW), and seminal vesicle (SVW) weights were measured. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and androgens were quantified by radioimmunoassay. Results indicate no significant change in TW or spermatogenesis. Spermatozoa were first seen in the lumen of 10% of seminiferous tubules at 35 days of age in both LD and LL rats and by 42 days of age, 80% of tubules from both LD and LL rats contained spermatozoa in the lumen. A highly significant depression in accessory structure development (VPW, SVW) was observed as a result of LL exposure. Serum FSH levels in LL rats were depressed on days 45, 51, 55, and 58 but elevated at 79. Serum PRL concentrations were elevated in LL rats on days 41, 55, 58, 63, and 79, whereas serum androgen levels were depressed on days 58, 63, and 79. Results suggest that exposure to LL results in delayed maturation of the accessory structures in the reproductive system of the male rat possibly as a result of reduced FSH or elevated PRL levels, which in turn may modify the rate and pattern of LH and/or androgen secretion.
Evidence of 5-HT participation in vagal inhibitory pathway to opossum LES.
Authors: Rattan S , Goyal R K
Published: December 2017

Studies were performed in anesthetized opossums to investigate the nature of vagal-stimulated sphincter relaxation, which is resistant to antagonism by a combination of hexamethonium and atropine. The sphincter pressures were measured with water-filled and continuously perfused catheters anchored in the lower esophageal sphincter. Neither increase in the doses of hexamethonium and atropine nor addition of diphenhydramine further modified the vagal response. However, administration of 5-methoxydimethyltryptamine in the presence of hexamethonium and atropine abolished vagally stimulated sphincter relaxation. In animals pretreated with parachlorophenylalanine, addition of atropine and hexamethonium also abolished vagally stimulated sphincter relaxation. In the experiments in which lower esophageal sphincter relaxation on vagal stimulation was abolished, the local stimulation of intramural neurons still produced normal lower esophageal sphincter relaxation. These studies suggest that 5-hydroxytryptamine may participate in the vagal inhibitory pathway to the lower esophageal sphincter.
Intestinal contribution to secretion of very low density lipoproteins into plasma.
Authors: Risser T R , Reaven G M , Reaven E P
Published: December 2017

To resolve the question of the magnitude of the intestine's contribution to circulating very low density lipoproteins (VLDL), measurements of intestinal, hepatic, and total VLDL--triglyceride were made on the same animals or on animals studied under comparable conditions. Animals were examined in the fasted state and during infusion of a fat-free meal. Intestinal VLDL secretion was determined through timed collections of lymph from the mesenteric lymph duct; hepatic and total VLDL secretion rates were estimated by the accumulation of plasma VLDL after injections of Triton WR 1339. Results indicate that the intestine contributes only a minor portion (11%) of the amount of triglyceride entering into the plasma compartment in the fasted state. Although intestinal triglyceride production is increased by 50% (p less than 0.01) in fed rats, the overall contribution of the intestine is not significantly altered in fed rats and represents only 14--17% of total body VLDL secretion. Thus, although intestinal VLDL secretion can be modified experimentally, its total impact on endogenous triglyceride production in normotriglyceridemic rats is small.
Loss of glucagon suppression of feeding after vagotomy in rats.
Authors: Martin J R , Novin D , Vanderweele D A
Published: December 2017

Infusion of pancreatic glucagon through the hepatic-portal vein decreased short-term food intake in sham-vagotomized but not in subdiaphragmatically vagotomized rats. Measurement of hepatic glycogen storage showed that vagotomized rats maintain a lower glycogen level than control animals over the four fasting periods evaluated. To determine whether the absence of a glucagon effect on feeding in vagotomized rats was the result of the reduced amount of substrate for glycogenolysis, vagotomized rats were not fasted and control animals were food deprived for 8h to produce comparable hepatic glycogen levels. Hepatic-portal infusion of glucagon into these differentially fasted animals suppressed feeding in control rats but not in vagotomized rats. It is concluded that the ineffectiveness of glucagon in suppressing feeding in vagotomized rats is not due to reduced concentration of hepatic glycogen. Instead, it is likely that glucagon induces glycogenolysis, but the glucose, or some other correlate of glycogen breakdown, loses its ability to produce satiety subsequent to vagotomy.
Insulin binding and effects in isolated soleus muscle of lean and obese mice.
Authors: Le Marchand-Brustel Y , Jeanrenaud B , Freychet P
Published: December 2017

To get some insight into the mechanisms of insulin resistance in obesity, insulin binding and biological effects were investigated in soleus muscles isolated from normal and obese mice. Basal and insulin-stimulated 2-deoxyglucose uptake were measured at the steady state of insulin binding. The results were consistent with the concept of spare receptors, i.e., maximal insulin effect was achieved when only about 20% of total receptors was occupied. When similar studies were applied to muscles of gold thioglucose obese or genetically obese (ob/ob) mice, and compared to lean controls: a) insulin binding was decreased; b) the insulin dose-response curve of 2-deoxyglucose uptake was shifted to the right; c) maximally insulin-stimulated 2-deoxyglucose uptake, glycolysis, and glycogen synthesis were markedly decreased. Insulin binding and effects returned toward normal after a 40-h fast in obese mice. These results point to two loci for the insulin resistance of skeletal muscle in obesity: 1) a decrease in the number of insulin receptors, which results in a diminished insulin sensitivity; and 2) one or more alterations beyond receptor that are responsible for the decreased responsiveness of the tissue to insulin and appear to play a major role in the insulin resistance of muscle in obesity.
A potential artifact in use of a new technique for rapid brain removal.
Authors: Wong K L , Tyce G M
Published: December 2017

New techniques are are continuously being developed to obtain animal brain tissue that is as close as possible to its in vivo status. The brain-blowing technique provides a swift freezing of brain tissue (within 1 s) in which postmortem changes have been said to be minimal. Higher concentrations of glucose were present in brain samples removed by this method than have previously been found when the brain was frozen in situ, but at the same time the plasma levels of glucose were higher. It is suggested that, although the procedure did not appear to involve any stress, the hyperglycemia was stress related. Modifications of the procedure are described, by which these changes in blood glucose have been minimized.
Histamine receptors in mesenteric circulation of the cat and rat.
Authors: Guth P H , Smith E
Published: December 2017

This study was designed to ascertain the types and functions of histamine receptors in the mesenteric circulation of the cat and rat. Superior mesenteric artery (SMA) flow was measured via an electromagnetic probe in the cat and intestinal submucosal arteriolar diameter by an image-splitting in vivo microscopy technique in the cat and rat. Histamine infusion into the SMA caused dose-dependent decreases in mesenteric vascular resistance. Mepyramine, an H1 receptor antagonist (H1A), inhibited this effect, displacing the histamine dose-response curve to the right. Metiamide, an H2 receptor antagonist (H2A), alone had no effect, but in the presence of H1A caused further displacement of the curve to the right. In both the cat and the rat, histamine superfusion dilated the submucosal arterioles. H1A attenuated this effect. H2A alone had no effect, but in the presence of H1A there was nearly complete inhibition of the histamine effect. In conclusion, both H1 and H2 histamine receptors, both subserving vasodilatation, are present in the mesenteric circulation and the H1 receptor effect predominates.
Permissive effect of ATP on insulin-stimulated sugar transport by rat soleus muscle.
Authors: Yu K T , Gould M K
Published: December 2017

The stimulatory effect of insulin (0.1 U/ml) on D-xylose uptake was progressively lost when rat soleus muscles were preincubated at 37 degrees C under anaerobic conditions for longer than 30 min; after 90 min these muscles were completely insensitive to insulin. This effect was associated with the loss of muscle ATP. When the breakdown of ATP was retarded either by lowering the preincubation temperature or by preincubation with 5 mM glucose, the effect of insulin in anaerobic muscle was correspondingly prolonged. Under certain conditions, externally added ATP promoted an effect of insulin in otherwise insulin-unresponsive muscles. This effect was small in magnitude and was complicated by the degradation of the added ATP in the incubation medium and by the fact that ATP also tended to inhibit insulin-stimulated xylose uptake. These results indicate that there is a relationship between insulin-stimulated sugar transport and muscle ATP levels. This supports the proposal that there may be some ATP-dependent reaction(s) involved in the mechanism whereby insulin promotes the process of muscle sugar transport.
Bicarbonate secretion and solute absorption in forestomach of the llama.
Authors: Rübsamen K , Engelhardt W V
Published: December 2017

Bicarbonate appearance in the lumen and its relationship to solute absorption were studied in a Pavlov pouch in the cardiac region of the first compartment of the llama forestomach. HCO3- appearance showed no diurnal variation. HCO3- accumulation was highly dependent on the pH of the solution used. The HCO3- ion probably is formed from CO2 diffusing into the lumen from the serosal side, as a result of cell metabolism and of OH- ions. HCO3- accumulation was closely related to volatile fatty acid (VFA) absorption. The ratio of HCO3- appearance to VFA absorption depended on the pH of the solution. At a pH of 6.6, about 0.1 mol HCO3- and, at a pH of 7.8, 0.9 mol HCO3- appeared per mole absorbed VFA, indicating that at slightly alkaline pH nearly all H+ ions required for the nonionic absorption of VFA appeared to be delivered from the dissociation of H2CO3. Bicarbonate gain and VFA absorption were increased when animals were not fed for 48 h. Sodium absorption was related to VFA as well as water absorption.
Parallel pathways for ion transport across rat gastric mucosa: effect of ethanol.
Authors: Dawson D C , Cooke A R
Published: December 2017

Transmural fluxes of 22Na or 36Cl across the isolated rat gastric mucosa were measured simultaneously with [3H]mannitol in an attempt to separate transmural ionic movement into cellular and noncellular components. The relationships between mannitol flux and the fluxes of Na and Cl are characteristic of simple diffusion, suggesting that mannitol traverses the isolated epithelium largely via noncellular pathways. The total tissue conductance can be described as the sum of two components, one of which is highly correlated with the transmural mannitol flux and presumably represents the conductance of a noncellular leak path. The cellular components of the mucosa-to-serosa Na flux and of both Cl fluxes are highly correlated with the short-circuit current. Exposure of the mucosal surface of the epithelium to 4% ethanol reduces the short-circuit current and increases the electrical conductance. Ethanol inhibits the active transport of Na and Cl and increases the apparent permeability of noncellular pathways for transmural ionic diffusion.
Contribution of dehydroepiandrosterone and its sulfate to estradiol in baboon pregnancy.
Authors: Schut H A , Pepe G J , Chez R A , Townsley J D
Published: December 2017

The metabolic clearance rates (MCR), conversion ratios (C), interconversion (rho), production rates (PR), secretion rates (SR), and relative contributions of maternal dehydroepiandrosterone (D) and D-sulfate (DS) to serum estradiol (E2) were determined in five pregnant baboons (Papio papio; 154-167 days gestation, term = 184 days) by constant intravenous infusion of [3H]DS and [14C]D. MCR-D (mean +/- SE) was greater (39.2 +/- 3.3 1/day.kg, P less than 0.001) than MCR-DS (3.1 +/- 0.3 1/day.kg). Because C-D leads to DS (5.460 +/- 0.461) exceeded (P less than 0.001) C-DS leads to (0.006 +/- 0.001), rho-DS leads to DS was greater (42.5% +/- 3.0%, P less than 0.001) than rho-DS leads to D (7.8 +/- 1.0%). C-D leads to E2 was greater (0.256 +/- 0.040) than C-DS leads to E2 (0.002 +/- 0.000). Using these values and serum levels of D (2.46 microgram/100 ml) and DS (18.9 microgram/100 ml) reported previously, SR and PR of D and DS were calculated. Of the total D produced (11.5 microgram/min), 98% was secreted, whereas only 32% of DS produced (7.1 microgram/min) was due to secretion. Using the serum D and DS levels and their conversion to E2, it was calculated that 89.7% of serum E2 was formed directly from D, 4.4% from D via DS, 1.8% from DS directly, and 4.1% from DS via D. It is concluded that, in spite of the low serum D level resulting from a high MCR, the large SR-D and more efficient conversion of D to E2 makes D, and not DS, the major circulating estrogen precursor in late baboon pregnancy.
Skeletal mass in postmenopausal women.
Authors: Aloia J F , Cohn S H , Ross P , Vaswani A , Abesamis C , Ellis K , Zanzi I
Published: December 2017

The techniques of photon absorptiometry of the radius and total body neutron activation analysis were used for the determination of bone mineral content and total body calcium, respectively. The subjects consisted of 71 normal women who were 1-5 yr postmenopausal and 44 osteoporotic women who had crush fractures of the dorsal spine. Both bone mineral content and total body calcium were corrected for age and body size by using the ratio of observed values to those predicted from previously derived equations. Discrimant analysis involving both osteoporotic and normal postmenopausal women resulted in the successful assignment of 81% of the 115 subjects to their correct group. Statistical analyses of the distribution of the bone mass of the postmenopausal women yielded no evidence to support the hypothesis that a subgroup exists with bone mass levels markedly different from the remainder of the women.
Importance of bicarbonate in bile salt independent fraction of bile flow.
Authors: Hardison W G , Wood C A
Published: December 2017

The bile salt independent fraction (BSIF) of canalicular bile flow from the isolated rat liver perfused with bicarbonate-free perfusate is 50% of that from the liver perfused with bicarbonate-containing perfusate. HCO3-excretion is nearly eliminated and Na+ and Cl- excretion is reduced 50%. Replacement of HCO3- into perfusate increased bile flow by 0.3 microliter/g.min without changing bile acid excretion rate. 5.5-Dimethyl-2,4-oxazolidinedione (DMO) produced a similar effect. DMO was passively distributed between bile and plasma. The data indicate that a bicarbonate transport mechanism is responsible for production of up to 50% of the BSIF. Another weak acid, N-5[5-(2-methoxyethoxy)-2-pyrimidinyl]sulfamoylbenzene (glymidine), was rapidly excreted into bile and increased bile flow by over 2.0 microliter/g.min. Glymidine is probably excreted by an independent organic anion transport mechanism, and any effect on the bicarbonate transport mechanism is obscured. Canaliculus-enriched hepatocyte membrane fractions contained no HCO3-stimulated ATPase activity. Either this enzyme is unimportant in hepatocyte bicarbonate transport or transport occurs across membranes other than the bile canalicular membrane.
Protein turnover in man measured with 15N: comparison of end products and dose regimes.
Authors: Waterlow J C , Golden M H , Garlick P J
Published: December 2017

Whole-body protein synthesis was measured with [15N]glycine in malnourished and recovered infants and in obese patients. Comparisons were made: 1) between results obtained with single (S) and repeated (R) oral dosage of tracer; and 2) between urea and ammonia as end products. In the infants S and R gave similar values for the synthesis rate. With both methods of dosage, the values obtained with NH3 as end product were about two-thirds of those with urea. It is suggested that the cause of this result is that glycine contributes preferentially to the formation of urinary NH3. With NH3 as end product, a collection period of 12 h has been found to be suitable. With urea it is not possible to define an appropriate collection period. The combination of single dose of [15N]glycine with urinary NH3 as end product provides a simple method for measuring whole-body protein synthesis under clinical and field conditions. It can be repeated at short intervals and can give useful comparative information provided that conditions are carefully standardized. The reproducibility so far is +/- 13%.
Glucose inhibition of 45Ca efflux from pancreatic islets.
Authors: Gylfe E , Buitrago A , Berggren P O , Hammarström K , Hellman B
Published: December 2017

Pancreatic islets were microdissected from ob/ob mice, loaded for 2 h with 45Ca and perfused with calcium-deficient medium. Irrespective of the glucose and calcium concentrations in the loading medium, increased glucose in the perfusion medium resulted in reduced amounts of radioactivity in the perfusate. A glucose inhibition of 45Ca washout was also evident when the specific radioactivity of the islets approached that of the labeling medium, indicating that the effect was not simply due to isotopic dilution. The depression of 45Ca washout diminished after culture of the islets in a serum-free medium and it was absent in islets taken from mice homozygous for the gene diabetes. The glucose effect became less pronounced when 50 micron D-600, an inhibitor of the calcium inward transport, was added to the calcium-deficient perfusion medium and abolished in the presence of 20 mM Ca-EGTA. The inhibition of the 45Ca washout observed is not necessarily due to a direct glucose interaction with the outward calcium transport but may also result from stimulation of the uptake and intracellular trapping of the cation.
Glucocorticoids and regulation of phosphoenolpyruvate carboxykinase activity in rat brown adipose tissue.
Authors: Feldman D , Hirst M
Published: December 2017

Studied were performed to examine the factors that might regulate phosphoenolpyruvate carboxykinase (PEPCK) activity in rat brown adipose tissue (BAT) and to determine the role played by glucocorticoids in regulating this enzyme. Comparison was made to white adipose tissue (WAT) where PEPCK activity is known to be glucocorticoid regulated. PEPCK activity in BAT did not respond to adrenalectomy or dexamethasone, whereas WAT activity was increased and decreased, respectively, by these maneuvers. Three conditions were found in which BAT PEPCK activity was stimulated: 1) fasting, 2) feeding a high-fat/low-carbohydrate diet, and 3) during the neonatal period. In each case glucocorticoid treatment prevented the stimulation in PEPCK activity and restored the enzyme to base-line levels. In conditions 1 and 2, enzyme activity was also stimulated in WAT, but in contradistinction to BAT, glucocorticoid administration reduced activity to low levels significantly below base-line activity. Two conditions were found which suppressed PEPCK activity in BAT: exposure to a cold environment and feeding a high-protein/low-fat diet. WAT PEPCK was unaltered by exposure to cold. Thus, differences in PEPCK regulation between BAT and WAT were demonstrated, and the response to glucocorticoids was unique in BAT.
Plasma ammonia and liver ornithine transcarbamoylase activity in zinc-deficient rats.
Authors: Rabbani P , Prasad A S
Published: December 2017

The effects of zinc deficiency on the activity of hepatic ornithine carbamoyltransferase (OCT) and plasma ammonia were studied in rats. One group received (ad libitum) zinc-deficient diet containing 2 ppm zinc and the other group received a diet containing 110 ppm zinc (group pair-fed control) equal to the amount consumed by zinc-deficient rats during the previous 24 h. Rats were killed at weekly intervals. Blood urea nitrogen (BUN), plasma ammonia, and hepatic OCT activity were determined. By end of the 1st wk on zinc-deficient diet, the plasma ammonia levels became significantly higher than those of the controls and remained elevated thoughout the study period. BUN increased initially for 2 wk in the deficient rats, but by the end of 4 wk the levels were lower than in the controls. The hepatic OCT activity in deficient animals was significantly lowered as compared to the controls by the 3rd wk. It is concluded that an increase in plasma ammonia may occur as a result of deficiency of zinc.
Action of PMSG and asialo-PMSG on rat Leydig and granulosa cells.
Authors: Moyle W R , Erickson G , Bahl O P , Christakos S , Gutowski J
Published: December 2017

Highly purified pregnant mares serum gonadotropin (PMSG) was nearly as potent as ovine luteinizing hormone (LH) and human follicle stimulating hormone (hFSH) when bioassayed in vitro in systems known to respond primarily to LH or FSH. An analogue of human chorionic gonadotropin treated with neuraminidase, galactosidase, beta-N-acetylglucosaminidase, and mannosidase (hCG) inhibited the stimulatory effects of hCG, LH, and PMGS on cAMP accumulation in rat Leydig cells but did not inhibit the stimulatory effects of FSH or PMSG on cAMP accumulation in ovarian granulosa cells obtained from immature rats fed diethylstillbestrol. Thus PMSG appeared to form functional complexes with both LH and FSH receptors and may be unique among mammalian gonadotropins. Treatment of PMGS with neuraminidase increased its potency nearly tenfold in vitro apparently by increasing its affinity for both LH and FSH receptors. Although the kinetics of PMSG binding were not investigated with radiolabeled materials, indirect functional binding studies are described that suggest that hCG more rapidly forms stable hormone-receptor complexes than PMSG, asialo-PMSG, FSH, and LH when all hormones are incubated under the same conditions.
Effect of somatostatin on myoelectrical activity of small bowel.
Authors: Thor P , Król R , Konturek S J , Coy D H , Schally A V
Published: December 2017

Somatostatin, a growth hormone-release inhibiting hormone, has been found to be a powerful inhibitor of gastric and pancreatic secretion as well as of hormone release in the digestive system. This study was undertaken to determine the influence of somatostatin on the myoelectrical activity pattern of the small bowel. Three conscious dogs were prepared with electrodes spaced 25 cm apart along the entire small intestine. Intravenous infusions of somatostatin were administered in various doses (0.6--5.0 microgram/kg.h) while spike activity and slow waves were recorded under fasting conditions, after a meat meal, or during intravenous infusion of gastrin, caerulein, or insulin. Somatostatin at a dose of 0.6 microgram/kg.h almost doubled the frequency of the interdigestive myoelectric complex. Somatostatin in fed dogs caused a dose-dependent decrease of the normal fed spike activity, and at higher doses it induced a pattern like that seen in fasting animals. The slow-wave frequency in both fasted and fed conditions was not changed significantly. We conclude that somatostatin given under basal conditions increases the frequency of the interdigestive complex and, when administered after feeding, converts the fed-type pattern to the fasted-type pattern. It may therefore play a promoting role in initiating the interdigestive myoelectric complex.
Diet-induced adipocyte number increase in adult rats: a new model of obesity.
Authors: Faust I M , Johnson P R , Stern J S , Hirsch J
Published: December 2017

Adult rats of various strains became obese when they were fed a highly palatable diet for several months. Analysis of their adipose tissue morphology revealed increases in both adipocyte size and number in most depots. Reintroduction of an ordinary chow diet to such animals precipitated a period of weight loss during which only mean adipocyte size returned to normal. Adipocyte number remained at the elevated level achieved during the period of weight gain. Thus, transient dietary obesity in rats results in a persistent obesity of a purely hyperplastic, nonhypertrophic form. Furthermore, the persistence of the cell number increase suggests that it is the result of proliferation or differentiation rather than of only an increase in the lipid content of a pool of very small and normally undetected adipocytes. An analysis of adipose tissue morphology changes during the course of diet-induced weight gain suggests that the achievement of some specific mean adipocyte size triggers the events that culminate in adipocyte number increase. What mechanisms may link adipocyte size to the formation of new adipocytes remains unknown.
Influence of taurocholate, taurochenodeoxycholate, and taurodehydrocholate on sulfobromophthalein transport into bile.
Authors: Binet S , Delage Y , Erlinger S
Published: December 2017

To test the hypothesis that incorporation of sulfobromophthalein (BSP) into mixed micelles could account for the increase in its biliary transport maximum (Tmax) by bile salts, we have compared in hamsters the influence on BSP Tmax of taurocholate and taurochenodeoxycholate (two micelle-forming physiological bile salts) to that of taurodehydrocholate, a bile salt which, in vitro, does not form micelles. In a first series of experiments, it was observed that taurocholate and taurochenodeoxycholate increased the secretion of phospholipid (40 and 53%, respectively), and cholesterol (50 and 110%, respectively), whereas taurodehydrocholate decreased the secretion of phospholipid (-31%) and cholesterol (-43%). This result suggests that, in vivo, taurodehydrocholate or its metabolites do not form mixed micelles. In a second series of experiments, it was seen that the three bile salts induced a similar increase in BSP Tmax (63% with taurocholate, 52% with taurochenodeoxycholate, and 51% with taurodehydrocholate). These results provide circumstantial evidence for the hypothesis that mixed micelle formation is not an important determinant of maximal BSP secretion into bile.
Increased glucagon secretion in protein-fed rats: lack of relationship to plasma amino acids.
Authors: Eisenstein A B , Strack I , Gallo-Torres H , Georgiadis A , Miller O N
Published: December 2017

This investigation was designed to test the hypothesis that protein feeding stimulated glucagon secretion because amino acids liberated during protein digestion function as glucagon secretagogues. Rats were fed high-protein (HP) or control diets for 9--10 days and blood taken from the aorta or portal vein (PV) at 0800, 1300, 1700, 1900, 2100, and 2300 for determination of amino acids, glucose, insulin, and glucagon. Glucose, insulin, and glucagon of control rats showed little change. In HP rats, PV glucose rose during fasting (0800-1700) and declined during feeding (1700-0800), changes that reflected alterations of glucagon and insulin secretion. PV glucagon in HP rats that was elevated 2--4 times rose during fasting, whereas PV and arterial amino acids declined. HP feeding caused enhanced glucagon release that was associated with increased amino acids in PV and arterial plasma, especially the branched-chain group. Although these findings suggest that protein feeding promotes glucagon release because branched-chain amino acids are elevated, these amino acids are known to have little effect on alpha cell function. Thus, we conclude that protein feeding influences glucagon secretion through some mechanism other than increased blood amino acid levels.
Effect of pulseless perfusion on gastrointestinal blood flow and its distribution.
Authors: Shoor P M , Griffith L D , Dilley R B , Bernstein E F
Published: December 2017

The effect of nonpulsatile (NP) arterial perfusion on gastrointestinal organ blood flow and intraorgan flow distribution was studied in 10 anesthetized (pentobarbital) dogs utilizing the radionuclide-labeled microsphere (15 micrometer) technique. Measurements of flow to the stomach, small intestine, and colon were made during a pulsatile perfusion control period and after 1- and 2-h periods of NP perfusion with a centrifugal left ventricular bypass pump (Medtronic). Total gastric blood flow (0.178 +/- 0.021 ml/min per g) as well as the partitioning of that flow between gastric subsegments such as antrum (17% of total gastric flow), body (83%), and mucosa (73%) was not significantly altered during the 2-h period of NP perfusion (P greater than 0.20). Similarly, flow to the intestine showed significant change during NP perfusion. Under conditions of equivalent hemodynamic states (mean perfusion pressure), nonpulsatile arterial perfusion results in no significant alteration in gastrointestinal blood flow or its intraorgan distribution.
Effect of synthetic C-terminal fragments of hGH on glucose oxidation by isolated islets.
Authors: Weerasinghe C , Bornstein J
Published: December 2017

The effect of polypeptides containing the human growth hormone sequence 177--191 on the glucose metabolism of isolated islets of Langerhans has been investigated. It has been found that such peptides accelerate the incorporation of hydrogen at carbon atom 5 into water while accelerating the flux (1-14C oxidation) through the pentose phosphate shunt and inhibiting the oxidation of [6-14C]glucose. The latter inhibition was found not to be due to inhibition of the pyruvate dehydrogenase complex, and it was further found that the previously demonstrated potentiation of glucose-induced insulin release by the peptides was independent of energy provision because none of the glyceraldehyde, pyruvate, or leucine could substitute for glucose. In view of the fact that the insulinogogue effect of this peptide is to potentiate the glucose stimulatory effect on islets, these phenomena may well be unrelated.
Drug uptake into everted intestinal sacs. I. Enhancement by hypertonicity.
Authors: Hurwitz A , Gutman Y
Published: December 2017

The transfer of the cationic drugs, pralidoxime (PAM) and tetraethylammonium, and anionic ampicillin from the mucosal-to-serosal sides of everted rat jejunal sacs is enhanced by mucosal hypertonicity. PAM uptake, which is proportional to initial mucosal concentrations up to 2.3 mM, is enhanced by mucosal hypertonicity due to addition of sodium, potassium, lithium and choline chloride, sodium sulfate, and the nonionic solutes, urea, sucrose, and mannitol. Bicarbonate, Tris, or phosphate buffer and the presence of magnesium and calcium do not affect this hypertonicity-induced acceleration of PAM passage. Serosal osmolality has no effect on transfer and mucosal hypertonicity is equally effective in the presence and absence of a transmural osmotic gradient. This observation and minimal changes in the concentration of inulin placed in the sacs suggest that fluid shifts and solvent drag are not responsible for the enhanced mucosal-to-serosal transfer of PAM from hypertonic buffer. Mucosal hypertonicity at 450 mosmol/kg causes reversible enhancement of PAM transfer, whereas the effect of 600 mosmol/kg cannot be reversed by replacing the tissue in isotonic buffer. The effect of osmotic manipulation on PAM transfer across the intestine thus differs from its effect on the passage of other ionized species and drugs across other epithelia.
Drug uptake into everted intestinal sacs. II. Inhibition of secretion by hypertonicity.
Authors: Hurwitz A
Published: December 2017

Mucosal hypertonicity, metabolic inhibitors, or absence of glucose and oxygen enhance mucosal-to-serosal influx of the cationic drug, pralidoxime (PAM), into sacs of everted rat jejunum in vitro. Conversely, efflux of PAM, which is twice the influx rate, is inhibited by mucosal hypertonicity or cyanide and iodoacetate. When sacs containing PAM, 0.87 mM, and glucose, 10 mM, were placed in identical drug- and sugar-containing mediums, the inside (serosal) concentration of PAM fell by over half in 120 min, whereas that of glucose more than doubled. Mucosal hypertonicity depressed PAM efflux and glucose influx regardless of serosal osmolarity. Although azide and mucosal hypertonicity each depressed glucose uptake and oxygen consumption while accelerating net PAM influx, azide more effectively depressed glucose and oxygen uptake, whereas hypertonicity caused greater acceleration of PAM uptake. Hypertonicity did not affect PAM binding to intestinal tissue. Varying mucosal pH did not change PAM or glucose uptake. Thus, mucosal hypertonicity apparently enhances net mucosal-to-serosal transfer of PAM by blocking its active secretion from serosa to mucosa.
Anion-stimulated ATPase activity of brush border from rat small intestine.
Authors: Humphreys M H , Chou L Y
Published: December 2017

Differential centrifugation of rat small intestinal homogenates produced a crude brush border (BB) fraction that was enriched 15-fold for the marker enzymes, alkaline phosphatase and sucrase; contamination with mitochondrial enzymes, monoamine oxidase and succinate dehydrogenase, was minimal. ATP hydrolysis by this BB fraction was stimulated by addition of several anions to the incubation medium: HCO3 and Cl were equally effective in this regard, with NO3, NO2, SO4, and acetate being less stimulatory. SCN and CNO inhibited ATPase activity, whereas the divalent anion SO3 was stimulatory at low concentrations (less than 25 mM) but inhibitory at 100 mM. Maximum anion stimulation was observed at a Mg concentration of 0.5 mM, and pH optimum was 8.5. Kinetic analysis showed that HCO3 increased the Vmax without altering the Km for ATP; the Ka for this effect of HCO3 was 35 mM. This enzyme activity was completely inhibited by 20 mM L-phenylalanine, 10 mM L-cysteine, and 3 mM EDTA, compounds that also inhibited intestinal alkaline phosphatase. These results demonstrate the presence of anion-stimulated ATPase activity in rat small intestinal brush border and suggest that this activity may be related to intestinal alkaline phosphatase. The role of this enzyme in intestinal transport is not known, but could relate to the regulation of intestinal absorption and secretion.
Determination of human pancreatic cationic trypsinogen in serum by radioimmunoassay.
Authors: Geokas M C , Largman C , Brodrick J W , Johnson J H
Published: December 2017

A specific radioimmunoassay has been developed for human pancreatic cationic trypsin. The assay has been employed for the determination of immunoreactive forms of pancreatic cationic trypsin in blood. The trypsin employed as radioiodinated tracer in the assay was inactivated with tosyl-L-lysine chloromethyl ketone (TLCK) to prevent binding of the tracer to the serum inhibitors while maintaining its immunoreactivity. The average normal serum level determined was 26 ng/ml, with a range of 12--41 ng/ml. Eight of nine patients with acute pancreatic inflammation had at least a 15-fold elevation of total serum immunoreactive cationic trypsin. Cationic trypsinogen and cationic trypsin bound to alpha1-antitrypsin cross-react strongly in the radioimmunoassay. Thus it is possible to measure these potential molecular forms of cationic trypsin in serum. When normal human serum was fractionated on Sephadex G-200, all of the immunoreactive material eluted as a single peak of approximately 23,000 mol wt. No cationic trypsin could be detected in association with alpha1-antitrypsin or alpha2-macroglobulin. The 23,000-mol-wt peak was definitively shown to contain trypsinogen by affinity chromatography and by activation with human enteropeptidase. The identification of cationic trypsinogen in blood implies that the zymogen is secreted into the circulation by the pancreas rather than entering the bloodstream via absorption from the intestine.
Differential effects of somatostatin analogues on alpha- and beta-cells of the pancreas.
Authors: Taborsky G J , Smith P H , Porte D
Published: December 2017

We examined the effect of somatostatin (SS) and its analogues on basal insulin and glucagon output from the right lobe of the in situ canine pancreas. Somatostatin (0.17 and 1.7 microgram/min, iv) significantly inhibited insulin (delta = -48 +/- 9% and delta = -88 +/- 3%) and glucagon (delta = -13 +/- 16%, P = NS and delta = -55 +/- 8%). Des-Asn5-SS Significantly inhibited insulin (delta = -40 +/- 9% and delta = -92 +/- 3%) but not glucagon (delta = +35 +/- 18% and delta = +4 +/- 12%). Likewise, [D-Ser13]-SS significantly inhibited insulin (delta = -40 +/- 14% and delta = -71 +/- 8%) with only slight inhibition of glucagon (delta = +26 +/- 15%, P = NS and delta = -16 +/- 6%, P less than 0.05). In contrast, [D-Cys14]-SS significantly inhibited both inhibited both insulin and glucagon. We conclude that structural changes of cyclic somatostatin can dissociate its ability to inhibit pancreatic insulin and glucagon secretion. Because the putative receptors on the pancreatic alpha- and beta-cell appear to recognize different configurations of the somatostatin molecule, it is suggested that the receptors themselves are different.
Stimulus-secretion coupling of glucose-induced insulin release. XXIX. Regulation of 86Rb+ efflux from perfused islets.
Authors: Boschero A C , Malaisse W J
Published: December 2017

Glucose provokes a dose-related, rapid, sustained, and rapidly reversible reduction in the fractional outflow rate of 86Rb+ from perfused pancreatic islets. This efflux probably corresponds to a passive movement driven by the electrochemical gradient of K+ across the plasma membrane and mediated by a native ionphoretic system. Indeed, it is facilitated by valinomycin or cell membrane depolarization, little affected by ouabain, and inhibited by verapamil or omission of extracellular K+. The effect of glucose upon 86Rb+ efflux does not appear to be directly attributable to changes in either glucose transport, plasma cell polarization, Na+ influx, cyclic AMP concentration, or insulin secretion. Although a modulatory role of intracellular Ca2+ on K+ conductance cannot be ruled out, the experimental data suggest rather that the glucose-induced modification of 86Rb+ fractional outflow rate is directly linked, for its major part, to metabolic events such as an increase in the rate of glycolysis and/or generation of reduced pyridine nucleotides.
Mesenteric lymph proteins in zinc-deficient rats.
Authors: Jacobs F A , Winter T W , Sandstead H H
Published: December 2017

Because zinc apparently has a role in amino acid utilization, we have studied possible consequences of zinc deficiency on the metabolism of amino acids in the intestinal mucosa by examining proteins transported via the mesenteric lymph in zinc-deficient and zinc-supplemented rats. Mesenteric lymph ducts were cannulated under pentobarbital, and on recovery the animals were fed [14C]leucine as a pulse dose by duodenal infusion. Protein output via intestinal lymph was generally constant over the infusion range studied. Total lymph protein output was not affected by zinc deficiency or supplementation. The electrophoretic pattern of the lymph protein revealed a protein band that migrated with the alpha2-globulins coincidental to zinc deficiency; the band disappeared after zinc supplementation. There was an inverse zinc-copper relationship in mesenteric lymph; duodenal infusion of zinc to deficient rats was followed by a decrease in lymph copper. Deficiency of zinc seems to have little influence on the quantitative aspect of protein carried in mesenteric lymph but seems to be involved with the nature of the protein in this body fluid.
Hepatic extraction of bile salts in conscious dogs.
Authors: Pries J M , Sherman C A , Williams G C , Hanson R F
Published: December 2017

The enterohepatic circulation of cholic acid conjugates (CAC) was studied in three conscious dogs by comparing the relationship of the concentration of CAC in portal, hepatic, and peripheral venous plasma samples collected simultaneously. The pool of CAC in each dog was labeled with 14C. Catheters were surgically placed in the jugular, left hepatic, and portal veins. Each dog was studied on 2 consecutive days, and each study consisted of a series of samples withdrawn from each catheter at 15-min intervals before and after gallbladder contraction with cholecystokinin. The concentration of CAC in the portal vein ranged from 3 micron (fasting) to 235 micron (after gallbladder contraction). In individual studies, the concentration of CAC increased four to sixfold. A linear relationship exists between the concentration of CAC in the portal vein to that in the hepatic and jugular veins. Thus, the fractional hepatic extraction of CAC is constant over the physiological range of the concentration of CAC in portal venous plasma. Mean extraction varied among the six studies from 0.618 +/- 0.072 (+/- 1 SD) to 0.983 +/- 0.010.
Antiphosphaturic action of 25 (OH) vitamin D3 in experimental Fanconi syndrome.
Authors: Popovtzer M M , Mehandru S K , Saghafi D , Blum M S
Published: December 2017

Renal handling of phosphorus was studied in the following groups of parathyroidectomized rats with maleate-induced Fanconi syndrome: 1) 6 rats receiving intravenous parathyroid hormone, 2) 6 rats receiving intravenous dibutyryl cyclic AMP (DBcAMP), 3) 6 rats undergoing volume expansion with saline, 4) 12 rats receiving intravenous 25 (OH)vitamin D3, 5) 12 rats with acute hypercalcemia induced by intravenous CaCl2, 6) 6 rats with phosphate deprivation, and 7) 6 rats receiving intravenous calcitonin. Parathyroid hormone and calcitonin failed to increase the urinary excretion of both cAMP and phosphorus. Likewise, DBcAMP failed to increase the urinary excretion of phosphorus. Extracellular volume expansion and hypercalcemia (serum calcium 12.9 +/- 0.7 mg/100 ml) did not alter the tubular reabsorption of phosphorus. In phosphate-deprived animals, the fractional excretion 0.16 +/- 0.05 (mean +/- SE) was lower than that in the control animals (maleate-treated without phosphate depletion), 0.46 +/- 0.04 (P less than 0.001). 25 (OH)vitamin D3 decreased the fractional excretion of phosphorus from 0.39 +/- 0.03 in the control (maleate-treated not receiving 25 (OH)vitamin D3) to 0.23 +/- 0.02 (P less than 0.001) in the experimental animals. The present study demonstrated an antiphosphaturic effect of 25(OH)vitamin D3 in experimental Fanconi syndrome; the mechanism of this action is not well understood.