bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for a histamine H2 receptor that inhibits pepsin secretion in the dog.
Authors: Hirschowitz B I , Hutchison G A
Published: December 2017

H+ and pepsin output were studied in four gastric fistula dogs with histamine and in five dogs with 4-methylhistamine (4(Me)H), an H2 histamine receptor agonist with little H1 effect. Each amine was given in 45-min incremental step doses to constitute full dose-response curves. Pepsin output was biphasic with both drugs. Peak pepsin output occurred at low doses (less than or equal to 5 microgram/kg-h) and progressive inhibition of output was seen at higher doses, but H+ output was stimulated at all doses. The H2 receptor antagonist, cimetidine, competitively inhibited H+ stimulation. The pepsin response to histamine or 4(Me)H was converted to a positive logsigmoid response when cimetidine was given at the same time. In the presence of cimetidine (1 mg/kg-h), the outputs of H+ and pepsin were positively correlated in the full histamine dose range. These data show that histamine effects on pepsin secretin are a mixture of stimulation and inhibition and that the receptor responsible for pepsin stimulation is of a high affinity, low Km, H2 type, whereas inhibition at high doses of histamine is probably mediated by a low affinity, high Km receptor, also H2 type.
Energetics of Na+-dependent sugar transport by isolated intestinal cells: evidence for a major role for membrane potentials.
Authors: Kimmich G A , Carter-Su C , Randles J
Published: December 2017

Intestinal epithelial cells isolated from 6-wk-old chickens maintain the capability for Na+-dependent concentrative accumulation of 3-O-methylglucose (3-OMG). Cells depleted of ATP exhibit a transient accumulation of 3-OMG in response to imposed Na+ gradients ([Na+]o greater than [Na+]i) or when transmembrane ion diffusion potentials (cell interior negative) are established. Phlorizin or lack of extracellular Na+ prevents formation of sugar gradients in every case. A nonconcentrative, non-Na+-dependent sugar transport system is also operative in these cells. The latter system is inhibited to various degrees by phloretin, theophylline, cytochalasin B, and a variety of flavonones and flavones, including apigenin. These agents also act to inhibit efflux of sugar from the cell via this pathway. The concentrative system normally operates against a "leak" of sugar through the nonconcentrative carrier. If the passive system is made inoperative by any of the agents named above, a significant enhancement of steady-state sugar gradients maintained by the cells is observed. With cytochalasin B, gradients as large as 30-fold are established. The energy inherent in cellular Na+ gradients cannot account for sugar gradients of this magnitude unless both chemical electrical driving forces are considered. When the passive leak is maximmally inhibited, more than half of the total energy required must be derived from the membrane potential.
Rat adrenal cell sensitivity to angiotensin II, alpha-1-24-ACTH, and potassium: a comparative study.
Authors: Braley L M , Williams G H
Published: December 2017

Rat adrenal glomerulosa and fasciculata-reticularis cell sensitivity to comparable molar doses of angiotensin II (AII) (2.4 X 10(-12) to 2.4 X 10(-4) M) and ACTH (alpha-1-24-adrenocorticotropin) (3.5 X 10(-13) to 3.5 X 10(-8) M) as well as small increments in potassium (K+) (3.7 to 13 meq/liter) was investigated. Glomerulose cells responded to physiological levels of AII (2.4 X 10(-10) M) and alpha-1-24-ACTH (3.5 X 10(-12) M), whereas an increment of as little 0.3 meq/liter in medium K+ also significantly increased aldosterone production. Of the three stimuli, alpha-1-24-ACTH caused the greatest aldosterone rise (11 times control). Fasciculata-reticularis cells responded only to alpha-1-24-ACTH. Whereas the threshold sensitivity was no lower than with glomerulosa cells, the maximum response was significantly greater (63 times control). These findings are consistent with findings documented in vivo in man, suggesting that the control of aldosterone secretion is similar in these two species.
Mechanism of production of intestinal secretion by negative luminal pressure.
Authors: Hakim A A , Papeleux C B , Lane J B , Lifson N , Yablonski M E
Published: December 2017

The relationships between luminal hydrostatic pressure and fluid transport by dog jejunum in vivo studied as a sheet in the Wells clamp were compared with quantitative predictions from a model proposed for the mechanism of the secretion produced by elevated venous pressure. According to the model, the secretion produced by increasing venous pressure and the secretion produced by negative luminal pressure are both passive filtrates contingent on a transepithelial pressure of a few centimeters of H2O. We consider that the agreement between the observed and predicted responses to luminal pressure provides strong support for the model. In particular, a) the observations displayed a predicted gross asymmetry in rates of fluid transfer with isotonic fluids depending on whether the luminal pressure was positive or negative; b) the observed magnitude of the negative luminal pressure required for the onset of secretion agreed with predictions; and c) the secretion contained significant amounts of protein at about 25% of the plasma concentration.
Inhibition of dopamine-induced release of growth hormone by thyrotropin-releasing hormone.
Authors: Steiner R A , Illner P , Marques P , Williams D , Shen L , Edwards L , Gale C C
Published: December 2017

The effects of thyrotropin-releasing hormone (TRH) and dopamine (DA) on serum growth hormone (GH) levels were examined in the adolescent male baboon. Intravenously administered DA (40 microgram/kg-min-1 for 20 min) raised serum GH and glucose and lowered serum insulin concentrations but caused no increase in blood pressure. Concomitant intravenous infusion of TRH at 2 doses (96 ng/kg-min-1 and 40 microgram/kg-min-1 for 20 min) blocked the DA-induced increase in serum GH. The relatively low effective doses of TRH used to suppress the DA-induced GH increase suggest an interaction with catecholamines at the hypothalamic and/or pituitary to influence GH release.
Effect of luminal constituents on vitamin K1 absorption into thoracic duct lymph.
Authors: Hollander D , Rim E
Published: December 2017

Lymphatic appearance rate of [3H] phylloquinone was studied in unanesthetized rats with cannulated bile and lymph ducts. A linear relationship (y= -44.9 + 10.2x, r=0.99) was found between the rate of the compound's infusion into the duodenum and its appearance rate in the lymph. Increasing the taurocholate infusate concentrations from 5 to 15 mM increased phylloquinone appearance rate in the lymph from 6.47 +/- 1.82 to 24.14 +/- 1.20 pmol/min (P less than .01). Varying the infusate pH from 4.35 to 8.0 did not change lymphatic appearance rate of vitamin K1 or lymphatic flow rate. Addition of short-chain fatty acid (butyrate) to the infusate enhanced the total absorption of vitamin K1 into the bile and lymph, whereas the addition of polyunsaturated fatty acids inhibited the total absorption of the vitamin. These experiments delineate some factors that modify the extrusion rate of vitamin K1 out of the enterocyte into the lymphatic circulation and add information regarding this phase of the absorptive pathway of lipids.
Changes in red cell space of bone in hypocalcemic states: studies in rat femur.
Authors: Lien J , Kaye M
Published: December 2017

With the use of technetium-99m-labeled red cells, the red cell space of the femur was found to be increased in rats fed a 0.01 percent Ca diet for 4 wk, at which time they were also hypocalcemic. Rats fed the same diet for 2 wk did not demonstrate hypocalcemia nor hypervascularity of the femur. Thyroparathyroidectomized (TPTX) rats fed the calcium-deficient diet produced hypocalcemia nor hypervascularity as did TPTX rats fed a normal diet for 4 wk. However, bone vascularity was normal at 2 wk post-TPTX (normal diet) when the degree of hypocalcemia was less marked. Inhibition of prostaglandin synthetase with oral indomethacin 0.2 mg/100 g per 12 h for 60 h did not alter the red cell space estimates but did increase bone blood flow in both normal and calcium-deficient animals. Acute restoration of normocalcemia with CaCl2 orally in the calcium-deficient rats did not revert the bone hypervascularity. The evidence suggests that in these models of hypocalcemic states, the rise in the vascular space of bone does not result from the influence of PTH, calcitonin, diet, or prostaglandins.
Reduced triglyceride secretion: a metabolic consequence of chronic exercise.
Authors: Simonelli C , Eaton R P
Published: December 2017

Chronic exercise training is recognized to reduce plasma lipid levels in man and animals, but the mechanism(s) mediating this phenomenon have not been defined. In the present study, we examined triglyceride (TG) production and disposal in vivo in a genetic model of human type IV hyperlipemia, the obese Zucker rat. Utilizing the normolipemic thin littermate as the control, we investigated endogenous production of TG utilizing the Triton methodology and peripheral disposal of an exogenous lipid emulsion utilizing Intralipid injection. In the sedentary state, the hyperlipemic obese Zucker rat demonstrated a threefold elevation in triglyceride secretion rate relative to the normolipemic thin littermate. After a 3-wk period of exercise training, a reduction of basal plasma TG concentration of 42% was associated with a 51% reduction in TG secretion rate, a change adequate to account for the hypolipemic response. Moreover, chronic exercise training also improved the ability to dispose of an Intralipid load. A similar reduction in TG production with reduced TG removal was observed in the thin normolipemic rats, a result that suggests that the lipid lowering response to exercise training may be predominantly mediated by reduced secretion of TG. The possible relationship between reduced TG secretion and alterations in the bihormonal axis of insulin and glucagon are discussed.
Transport characteristics of isolated newborn rabbit ileum.
Authors: Cooke H J , Dawson D C
Published: December 2017

Segments of ileum from newborn rabbits were mounted as flat sheets in Lucite chambers and transmural fluxes of Na, Cl, and alanine were measured in the absence of electrochemical potential gradients. In the presence of 140 mM Na, the ileum of the newborn exhibited a serosa-positive electrical PD and a corresponding short-circuit current (Isc) which was markedly enhanced by the addition of D-glucose of L-alanine to the mucosal solution. Alanine-induced increments in Isc were a saturable function of the mucosal alanine concentration. In the presence of Na, alanine was actively absorbed, and the net alanine flux was a saturable function of alanine concentration. When the Na in the bathing solutions was completely replaced by choline, Isc declined to near zero, and the response of Isc to mucosal alanine was abolished. In addition, active amino acid transport was abolished in the absence of Na. In the absence of alanine, the isolated ileum of the newborn actively absorbed Na and Cl, and the algebraic sum of the net movements of these ions accounted for Isc. In the presence of alanine, active Cl transport was abolished and Isc was equal to the net Na absorption. These results indicate that the ileum of the newborn rabbit is similar to that of the adult in its ability to actively absorb Na, Cl, and alanine, but differs from the ileum of the adult by having a greater passive permeability to ions and amino acid, and differs particularly with regard to the effect of mucosal alanine on transmural ion transport.
Biological function of metallothionein. V. Its induction in rats by various stresses.
Authors: Oh S H , Deagen J T , Whanger P D , Weswig P H
Published: December 2017

Induction of metallothionein (a Zn-binding protein) was investigated in liver and kidneys of rats under the following stresses: cold environment, hot environment, heat burn, strenuous exercise, and CCl4 intoxication. As markers of metallothionein (MT) synthesis, [14C]cystine and 65Zn were injected parenterally into rats, and MT in liver and kidney supernatants was separated on Sephadex G-75 columns. Among stresses tested, the greatest stimulations of MT synthesis in liver were observed under cold (315%), strenuous exercise (302%), and CCl4 intoxication (543%), as evidenced by increased amount of [14C]cystine and 65Zn incorporation into the MT fraction. In contrast to liver, only small responses were observed in MT synthesis in kidneys. There was a general decline in plasma Zn levels in rats under the stresses employed. However, no great differences were observed in Zn levels in whole liver and kidneys. The present study suggests that various unrelated physiological stresses, which are accompanied with a change in Zn distribution, increase the synthesis of MT in liver of rats.
Mechanism of lithium-induced hypercalciuria in rats.
Authors: Lau K , Goldfarb S , Grabie M , Agus Z S , Goldberg M
Published: December 2017

Chronic administration of lithium salts is associated with hypercalciuria in the rat. To study the renal and extrarenal mechanisms of this phenomenon, we utilized balance and clearance techniques in rats pair-fed diets with or without Li2CO3 (0.5 meq/day per rat). Lithium induced hypercalcemia (mean +/- SE: 5.40 +/- 0.09 VS. 5.06 +/- 0.05 meq/liter) and hypercalciuria (Ca/creatinine = 0.28 +/- 0.04 vs. 0.13 +/- 0.03) only during feeding. When CaCO2 supplement to a calcium-deficient diet was abruptly withdrawn, hypercalciuria was abolished. However, polyuria and polydipsia persisted. No significant changes in serum phosphate, urine phosphate, sodium, pH, or citrate were observed. Chronic parathyroidectomy (PTX) also abolished this effect. During clearance studies, fasting excretion of calcium was similar between treated and control animals. Superimposed acute PTX resulted in comparable changes, hence arguing against primary changes in renal calcium reabsorption or changes in parathyroid hormone effects on the renal tubule. Thus, lithium produces absorptive hypercalciuria by a mechanism dependent on intact parathyroid glands and adequate diet calcium, but independent of urine sodium, phosphate, or pH. The active component of gut calcium transport may be involved, possibly via alterations of vitamin D metabolism.
Magnesium-fluoride interrelationships in man II. Effect of magnesium on fluoride metabolism.
Authors: Spencer H , Kramer L , Wiatrowski E , Osis D
Published: December 2017

The effect of magnesium on the fluoride balance was investigated in man by determining metabolic balances of fluoride and magnesium in control studies and during magnesium supplementation. The magnesium intake averaged 264 mg/day in the control studies and 825 in the experimental studies. The studies were carried out during four calcium intakes that ranged from 200 to 2,200 mg/day and during phosphorus intakes ranging from 800 to 2,000 mg/day. The studies were carried out during a fluoride intake of about 4 mg/day that was due to the dietary fluoride content and the intake of water and during a high fluoride intake of 25 mg/day that was due to the addition of sodium fluoride. During the high magnesium intake, both the urinary and fecal magnesium excretions increased and the magnesium balances became more positive. These changes were not associated with any significant changes of either the urinary or fecal fluoride excretions or of the fluoride balances during the different intakes of calcium phosphorus, or fluoride.
Involvement of hepatic metallothioneins in hypozincemia associated with bacterial infection.
Authors: Sobocinski P Z , Canterbury W J , Mapes C A , Dinterman R E
Published: December 2017

Hypozincemia was induced in rats by Salmonella typhimurium and live vaccine strain Francisella tularensis (LVS) infections. Hepatic synthesis of zinc-binding proteins (ZBP) was studied in order to elucidate the mechanisms involved in the redistribution of zinc from plasma to liver occurring during infectious illness. ZBP, labeled in vivo with 65Zn, were isolated and identified as metallothioneins based, in part, on their heat stability, dimorphism, and amino acid composition. Cysteine was the major amino acid found in both forms of metallothionein and constituted 28-31% of total residues. The apparent half-life of these proteins as measured by disappearance of 65Zn was determined to be 19 h in a relatively mild infection (LVS) and 38 h in a more severe S. typhimurium infection. Results provide evidence that metallothioneins not only have the previously postulated regulatory role in normal zinc homeostasis but are intimately involved in the zinc redistribution occurring during the acute stage of infectious illness.
Uric acid metabolism in homozygous and heterozygous muscular dystrophic mice.
Authors: Dju M Y , Yü T F
Published: December 2017

The homozygous muscular dystrophic mice (dydy) were found to have significantly higher plasma uric acid than their heterozygous littermate controls (Dydy), and the Swiss albino mice. Because the rate of uric acid excretion did not compensate for the elevated plasma levels, U/P (urine/plasma) urate was lower in dydy mice. With RNA supplement, plasma and urinary urate were increased in both dydy and Dydy mice; again U/P urate was lower in dydy mice. It appears that the dydy mice to a certain extent are comparable to some gouty subjects, whose hyperuricemia is not accompanied by a corresponding increase in urinary uric acid. There was no difference in converting uric acid to allantoin either on basal diet alone or with RNA supplement. Oxonic acid effectively, though transiently, blocked the uricase activity in both dydy and Dydy mice resulting in hyperuricemia and hyperuricosuria with decreased allantoin. Uric acid content was increased markedly in the kidney without histological evidence of urate deposition, apparently related to the unsustained effect of oxonic acid, which was rapidly excreted.
Insulin secretion during acid-base alterations.
Authors: Rebolledo O R , Hernandez R E , Zanetta A C , Gagliardino J J
Published: December 2017

Insulin secretion under extracellular acid-base alterations (metabolic acidosis or alkalosis) was studied, by challenging in vitro perfused sodium pentobarbital-anesthetized-rat pancreases with glucose, arginine, and tolbutamide. Under our experimental conditions, the amount of insulin released was lower at pH 7.8 than the amount corresponding to the pH 7.4 control, in spite of the agent used to stimulate the pancreas. The effect of pH 7.0 on insulin secretion, however, depends on the type and concentration of the stimulus used. It enhances the secretion elicited by glucose (6.6 mM) and glucose plus arginine (6.6 and 10 mM, respectively). On the other hand, it reduces the beta cell response to glucose plus tolbutamide (3.3 mM and 400 microgram/ml, respectively), whereas the response to high glucose (16.6 mM) is reduced in the first phase and not affected in the second. According to these results, modifications of the extracellular pH, mainly at high levels, may interfere with a common process involved in insulin secretion, namely beta cell emiocytosis.
Transamination of branched-chain keto acids by isolated perfused rat kidney.
Authors: Mitch W E , Chan W
Published: December 2017

Isolated rat kidney perfused without substrate released serine, glycine, and taurine, and substantially smaller amounts of other amino acids. When branched-chain keto acids were added, the corresponding amino acids were released at rates amounting to 15-25% of keto acid disappearance. Perfusion with 2 mM alpha-keto-isovalerate or alpha-keto-beta-methylvalerate caused an increased glucose release amounting to 18-23% of keto acid disappearance. The activity of branched-chain amino acid transferase (BATase) was significantly stimulated by perfusion with the analogue of leucine, but not by perfusion with alpha-ketoglutarate, the analogues of valine or isoleucine, or with leucine itself. These findings document that the kidney converts branched-chain keto acids in part to the corresponding amino acids and suggest that the keto analogue of leucine may be involved in the control of renal BATase activity, thereby indirectly regulating the metabolism of branched-chain amino acids.
Hepatic insulin and glucagon extraction after their augmented secretion in dogs.
Authors: Röjdmark S , Bloom G , Chou M C , Jaspan J B , Field J B
Published: December 2017

Effects of intravenous arginine and cholecystokinin-pancreozymin (CCK-PZ) infusion on hepatic extraction of insulin (EI) and glucagon (EGG) and also on hepatic glucose output (HGO) were studied in anesthetized dogs. Because insulin and glucagon exert antagonistic effects on HGO, insulin:glucagon (I/GG) molar ratios were determined in the portal vein and also in peripheral vessels. During the arginine-CCK-PZ infusion the amount of insulin and glucagon coming to the liver increased 12- and 15-fold, respectively. In contrast EI decreased significantly from a control value of 62 +/- 6% to a nadir of 22 +/- 13%. EGG (control value 19 +/- 9%), however, was unaffected by arginine-CCK-PZ. The absence of any alteration in EGG cannot be attributed to the molecular heterogeneity of the immunoreactive glucagon. HGO increased fourfold in response to the pancreatic stimulation, whereas portal I/GG decreased significantly from 8.2 +/- 0.9 to 5.0 +/- 0.7. The concurrent femoral arterial I/GG (control 3.7 +/- 1.0) and mesenteric venous I/GG (control 2.1 +/- 0.5) increased significantly. These observations indicate that portal, but not peripheral, I/GG measurements reflect hepatic events in anesthetized dogs, probably because of the different extraction patterns for insulin and glucagon.
Feeding and metabolic patterns in rats with truncular vagotomy or with transplanted beta-cells.
Authors: Louis-Sylvestre J
Published: December 2017

The night- and daytime basal plasma insulin levels and insulin responses to an intravenous glucose load, basal blood glucose levels and rates of glucose uptake, and, finally, the diurnal patterns of blood glucose levels were investigated in normal compared to vagotomized Wistar rats. The same comparisons were made between normal and diabetic Lewis rats recovered after fetal pancreas transplantation in the kidney capsule. In an attempt to clarify the relationship between the metabolic and feeding diurnal patterns, a detailed study of the meal pattern of vagotomized and transplanted rats was performed. It was shown that 1) a truncular vagotomy abolished both the metabolic and feeding diurnal cyclicity; 2) both the metabolic and feeding diurnal rhythms were maintained in case of a selective denervation beta-cells. The relationship between the metabolic and feeding diurnal rhythms and the role of the vagus nerve are discussed.
Insulin binding and glucose metabolism in adipocytes of streptozotocin-diabetic rats.
Authors: Kasuga M , Akanuma Y , Iwamoto Y , Kosaka K
Published: December 2017

To investigate the mechanism of the cellular insulin insensitivity of diabetic rats, insulin binding, glucose transport, and glucose oxidation were studied in adipocytes from streptozotocin-diabetic rats. Increased insulin binding was found in cells from diabetic rats, and this was due to an increased number of insulin receptors rather than a change in receptor affinity. Basal and insulin-stimulated glucose oxidation was decreased in adipocytes from diabetic rats when the data are expressed in absolute terms or as percent increased above basal. Although the absolute rate of basal and insulin-stimulated glucose transport was decreased in adipocytes from diabetic rats, the percent increase above basal of insulin-stimulated glucose transport was not decreased. In conclusion, although the cellular insulin insensitivity exists in adipocytes from diabetic rats, the number of insulin receptors was increased, coupling between insulin receptors and the glucose transport system is intact in adipocytes from diabetic rats, and a defect in intracellular glucose metabolism rather than glucose transport plays a major role in the insulin insensitivity of adipocytes from diabetic rats.
Splanchnic glucose and muscle glycogen metabolism after glucose feeding during postexercise recovery.
Authors: Maehlum S , Felig P , Wahren J
Published: December 2017

Glucose (100 g) was ingested 15 min after bicycle exercise until exhaustion at a work load corresponding to 70% of maximal uptake (series 1), 14--15 h after an identical exercise period, no food being taken in the interval (series 2), and by nonexercised control subjects. Splanchnic glucose output in the exercised groups rose to values 50--300% greater than in controls, amounting to (over 135 min) 59 +/- 5 g in series 1 and 58 +/- 6 in series 2 compared to 28 +/- 6 in controls. The glycogen concentration of quadriceps muscle in series 1 was 65 +/- 2 mmol glycosyl U/kg wet wt before exercise, 16 +/- 13 at the end of work, and 32 +/- 4 at 135 min after glucose ingestion. In series 2, muscle glycogen concentration was 20 +/- 3 immediately after exercise and rose to 44 +/- 5 over the ensuing 14--15 h in spite of continued fasting. It rose to 56 +/- 3 at 135 min after glucose loading. Repletion of leg muscle glycogen after glucose feeding could account for 50--66% of total splanchnic glucose release. It is concluded that during postexercise recovery, a greater proportion of an oral glucose load escapes hepatic retention, allowing repletion of muscle glycogen to take precedence over hepatic glycogen repletion.
Effect of sequential infusions of glucagon and epinephrine on glucose turnover in the dog.
Authors: Saccà L , Sherwin R , Felig P
Published: December 2017

Conscious dogs were infused with 1) glucagon (3 ng/kg.min) alone for 120 min followed by glucagon plus epinephrine (0.1 microgram/kg.min) for 60 min and 2) epinephrine alone (150 min) followed by epinephrine plus glucagon for 90 min. Glucagon alone caused a 10--15 mg/dl rise in plasma glucose and a 45% increase in glucose production that returned to baseline by 75--120 min. After addition of epinephrine, glucose production rose again by 80%. Infusion of epinephrine alone resulted in unchanged plasma glucagon levels, a 60--70 mg/dl rise in plasma glucose, and an 80--100% rise in glucose production that returned to baseline by 60--120 min. When glucagon was added, glucose output promptly rose again by 85%. When glucagon was infused alone, there was a rise in glucose uptake, whereas, with epinephrine, glucose uptake failed to rise and glucose clearance fell by 35--50%. We conclude that 1) hepatic refractoriness to persistent elevations of glucagon or epinephrine is specific for the hormone infused; 2) epinephrine stimulates glucose production in the conscious dog in the absence of a rise in plasma glucagon; 3) the hyperglycemic response to glucagon or epinephrine is determined in part by accompanying changes in glucose utilization.
Amino acid transport in diaphragms from newborn rats: evidence for insulin resistance.
Authors: Riggs T R , Wise H D , Motz K L
Published: December 2017

Diaphragms from rats under 24-h-old did not show the well-known increased transport of alpha-aminoisobutyrate found in older tissues in respone to insulin in vitro. A small effect was apparent by 3 days, and stimulation increased as donor rats aged (up to 4--5 wk). One-day diaphragms also had greater uptake than older tissues, due to both decreased Km and elevated Vmax. The change in insulin sensitivity did not result from alteration in the transport system used by alpha-aminoisobutyrate because uptake showed characteristics of the A system at both 1 day and older. Results suggest instead that the 1-day tissues had been made insulin-resistant by high insulin levels in donor animals. Plasma insulin levels of 1-day-old rats were 5 times those of 5-day animals. Elevating the plasma insulin levels of 5-day or 25- to 35-day rats led to a decreased effectiveness of insulin in vitro in stimulating alpha-aminoisobutyrate transport into their diaphragms. In the older animals, the stimulation was inversely proportional to the plasma insulin level 2 h after insulin injection.
Effects of some autonomic drugs on duodenal smooth muscle.
Authors: Anuras S , Faulk D L , Christensen J
Published: December 2017

Longitudinal muscle strips (LMS) and circular muscle strips (CMS), 2 mm wide and 1.5--2 cm long, from opossum duodenum were exposed to some autonomic agonists. The cholinergic agonists, acetylcholine, carbachol, methacholine, and bethanechol stimulated only tonic contractions in LMS and tonic followed by phasic contractions in CMS. These effects were abolished by atropine 10(-6) M. The ED50S of all cholinergic agonists for LMS were significantly lower than for CMS. Norepinephrine caused initial contraction (abolished by phenoxybenzamine, 10(-4) M), followed by relaxation (abolished by propranolol, 10(-5) M), and isopropylnorepinephrine caused relaxation (abolished by propranolol, 10(-5) M) in both layers. There were no differences in relative potencies for adrenergic agonists between the layers. Tetrodotoxin did not affect the response to adrenergic agonists. Thus, the potency of cholinergic agonists is greater in longitudinal than in circular muscle, and the layers respond differently to cholinergic agonists. The alpha-adrenergic receptors mediate contraction and beta-adrenergic receptors mediate relaxation on the duodenal smooth muscle.
Physiological and behavioral responses to starvation in the golden hamster.
Authors: Borer K T , Rowland N , Mirow A , Borer R C , Kelch R P
Published: December 2017

Physiological and behavioral responses of adult hamsters to starvation were studied by measuring food intake, weight recovery, serum concentrations of glucose, insulin, free fatty acids and beta-hydroxybutyrate, and ketonuria in animals subjected to different weight losses, diets, and durations of fast. Hamsters were debilitated by fasts longer than 12 h or leading to greater than 20% weight loss. Hamsters' feeding patterns were unmodified by fasts ranging between 5 and 12 h and showed no circadian periodicity. Hamsters predominantly recovered from weight losses without increasing their food consumption (unless they were offered a diet of pellets and seeds) and without changing their meal patterns, at a rate of weight gain proportional to the magnitude of preceding weight loss if provided with uninterrupted access to food. By 8 h of fast, blood metabolites were indicative of mobilization of body fat. Hamsters are thus behaviorally unresponsive to duration of fast, but compensate physiologically for weight losses with proportional increases in the rate of weight gain.
Influence of somatostatin on glucagon- and epinephrine-stimulated hepatic glucose output in the dog.
Authors: Saccà L , Sherwin R , Felig P
Published: December 2017

Glucose kinetics were measured using [3-3H]glucose in conscious dogs during the infusion of: 1) glucagon alone; 2) glucagon plus somatostatin with insulin replacement; 3) epinephrine alone; and 4) epinephrine plus somatostatin with insulin and glucagon replacement. Infusion of glucagon alone resulted in a 10-15 mg/dl rise in plasma glucose and a transient 45% rise in glucose production. When somatostatin and insulin were added, a four- to fivefold greater rise in plasma glucose and glucose production was observed. Glucagon levels were comparable to those achieved with infusion of glucagon alone, whereas peripheral insulin levels increased three- to fourfold above baseline, suggesting adequate replacement of preinfusion portal insulin levels. Infusion of epinephrine alone produced a 40% rise in plasma glucose and a 100% rise in glucose production. When somatostatin, insulin, and glucagon were added to epinephrine, the rise in glucose production was reduced in 65% despite replacement of glucagon levels and presumably mild portal insulin deficiency. These findings suggest that somatostatin: 1) potentiates the stimulatory effect of physiologic hyperglucagonemia on glucose production independent of insulin availability and 2) blunts the stimulatory effect of physiologic increments of epinephrine independent of glucagon availability.
Effect of atropine and vagotomy on response of transplanted pancreas.
Authors: Solomon T E , Grossman M I
Published: December 2017

It is well established that atropine and vagotomy inhibit pancreatic enzyme secretion in response to intestinal stimulants such as fat or amino acids. These effects are usually attributed to interference with hypothetical vagal cholinergic mechanisms that facilitate release of cholecystokinin. To determine whether atropine or vagotomy interferes with release of humoral stimulants of pancreatic enzyme secretion, we studied their effect on protein secretion from an autotransplanted portion of pancreas in response to intestinal stimulants in dogs. The transplanted pancreas was as sensitive as the intact pancreas to stimulation by exogenous caerulein, a cholecystokinin-like peptide, and this response was not altered by atropine or vagotomy. Therefore, if vagotomy or atropine interferes with release of humoral pancreatic stimulants, they would be expected to reduce the response of the transplanted pancreas just as they do of the intact pancreas. Truncal vagotomy caused no significant change in protein secretion from the transplant in response to intestinal perfusion with sodium oleate or tryptophan. Atropine was tested only against sodium oleate and caused no change in response. We conclude that release of humoral pancreatic excitants of protein secretion in response to intestinal stimulants is not significantly changed by atropine or vagotomy.
Early insulin and glucagon response to subsequent pulses of arginine, glucose, and tolbutamide in normal man.
Authors: Greco A V , Manna R , Ghirlanda G , Altomonte L , Rebuzzi A G , Bertoli A
Published: December 2017

To determine the dynamics of insulin and of glucagon secretion in response to several sequential stimuli administered shortly after an arginine pulse (5 g), 20 nonobese, apparently healthy volunteers were given arginine (5 g), glucose (5 g), and tolbutamide (1 g) by rapid intravenous injection. The early insulin and glucagon area 0-8 min was studied. At the intervals and with the dosages used in this study, different stimuli with and without prestimulation with arginine did not lead to changes in early secretion of insulin. There was no exhaustion of the pool of insulin released after multiple sequential pulses. These results suggest a pattern in which stimulation induces a rapid release of insulin and activates the interchange between the stored and labile insulin pool; the 8-min interval is sufficient for the rapid return of the two compartments to a state of equilibrium. Also for glucagon, subsequent different stimuli did not exhaust glucagon release; nevertheless, glucagon is immediately suppressed by a submaximal glucose pulse.
Calcium dependency of glucagon release: its modulation by nutritional factors.
Authors: Leclercq-Meyer V , Marchand J , Malaisse W J
Published: December 2017

The calcium dependency of glucagon release by the perfused rat pancreas was investigated in the presence of different nutrients: glucose, arginine, and a mixture of "fumarate + glutamate + pyruvate" (FGP, 5 mM of each salt). At a 3.3 mM glucose concentration, FGP-induced glucagon release was inhibited by the removal of calcium or addition of verapamil. At a higher glucose concentration (16.6 mM), the glucagonotropic action of FGP was again inhibited by verapamil, but the removal of extracellular calcium enhanced transiently glucagon release. Comparable results were obtained when arginine (10 mM) instead of FGP was used to stimulate the alpha cell. These findings suggest that the glucagonotropic effect of FGP or arginine depends on the availability and inward transport of calcium, whereas extracellular calcium per se may be required for glucose to be sensed by the alpha cell as an inhibitor of glucagon secretion. Thus, the nutritional environment offered to the alpha cell may condition the expression of the different mechanisms involved in the control of glucagon release by calcium.
alpha-Sympathetic control of glucose output of mouse liver perfused in situ.
Authors: Seydoux J , Brunsmann M J , Jeanrenaud B , Girardier L
Published: December 2017

Electrical stimulation of perivascular nerve bundles of mouse liver perfused in situ at constant flow resulted in an increase of glucose production that was maximal at 20 Hz. The neurally induced glucose output was inhibited significantly by the beta-blocker propranolol, and to a considerably greater extent by the alpha-blockers, phenoxybenzamine and phentolamine. The effect of 20-Hz electrical stimulation could be matched by an infusion of norepinephrine at a concentration of 5 X 10(-7) M. It is suggested that the carbohydrate metabolism of the liver is controlled by its own nerve supply rather than by circulating catecholamines and that alpha-adrenergic receptors have a greater effect than beta-receptors on hepatic glucose production resulting from electrical and catecholamine stimulation.
Progesterone secretion and fetal development during prolonged starvation in the pig.
Authors: Anderson L L , Hard D L , Kertiles L P
Published: December 2017

Roles of ovarian progesterone secretion and maternal nutrition in fetal development were investigated in a species that normally experiences considerable embryonic and fetal mortality. Pregnancies were maintained in 81% of Yorkshire pigs during prolonged starvation (e.g., 40 days; 0 kcal/day, water only) in either the middle third (days 30-70) or last third (days 70-110) of gestation compared with 100% in full-fed controls (7,028 kcal/day). In spite of severe maternal deprivation, fetal survival rates averaged 65% in starved dams and 63% in controls; mean number of living fetuses was 9.9 in starved and 9.6 in control dams. Fetal growth was reduced by maternal starvation during the middle third, but not the last third of pregnancy. Placental insufficiency was the primary cause of reduced fetal growth and resulted in abortion in a few of the dams. Progesterone in peripheral serum of dams starved either during middle or late pregnancy was maintained at levels similar (P greater than 0.05) to those in controls. Abortion occurred in starved dams only when serum progesterone concentrations dropped to less than 10 ng/ml within 3 days before loss of conceptuses.
Extrasplanchnic effect of sulfobromophthalein (BSP) on plasma estrogen levels in the dog.
Authors: Collins D C , Balikian H M , Robinson H R , Preedy J R
Published: December 2017

The effect of the drug sulfobromophthalein (BSP) on plasma estrogens in the dog were studied during intravenous infusions of 3H-labeled estrogens. During [3H]estrone infusion, BSP administration caused a marked increase in arterial plasma levels of the radioactive conjugated estrogens, estrone glucosiduronate, estradiol-17 beta glucosiduronate(s), and estrone sulfate. Levels of the unconjugated estrogens, estrone and estradiol-17 beta, were substantially unaltered. Possible mechanisms were investigated. Splanchnic extraction of the conjugates did not change significantly during BSP administration, and renal excretion rose promptly in proportion to the plasma levels, thus virtually excluding decreased biliary or renal excretion. There was no net discharge of estrogen glucosiduronate radioactivity from adipose tissue or muscle following BSP. During [3H]estrone glucosiduronate infusion, BSP again caused an increase in plasma estrone glucosiduronate, thus excluding increased formation (of this conjugate, at least). BSP caused decreased extraction of estrone glucosiduronate by the hindlimb, indicating that decreased metabolism was the probable cause of the elevated plasma levels. BSP also caused decreased formation of unconjugated estrogens by the lungs, indicating that the decreased metabolism includes decreased hydrolysis of estrogen glucosiduronates.
Ascorbate and peroxidase changes during pregnancy in albino rat and Swiss mouse.
Authors: Agrawal P , Laloraya M M
Published: December 2017

From the 1st to 6th days of pregnancy in the rat, while the blastocyst is still in the fallopian tube, there is high peroxidase activity in the corpus luteum, the blastocyst, and there is high peroxidase activity in the endometrium. On day 8 of pregnancy, peroxidase activity in the corpus luteum begins to fall rapidly, and there is a sharp rise in the peroxidase activity of the uterine endometrium. In all these tissues an inverse relationship exists between peroxidase and ascorbate content. We suggest the involvement of the peroxidase-ascorbate system in the mechanism of the extended function of the corpus luteum during pregnancy and a role for free radicals in the process of implantation of the blastocyst in the uterus.
Hypothalamus-pituitary-thyroid axis interactions with pineal gland in the rat.
Authors: Brammer G L , Morley J E , Geller E , Yuwiler A , Hershman J M
Published: December 2017

We examined in the rat several possible relationships between the pineal gland and the hypothalamus-pituitary-thyroid axis. The pineal gland, the retina, and the hypothalamus exhibited a diurnal rhythm in thyrotropin-releasing hormone (TRH) content with peak values occurring around 1200 h. This rhythm in the hypothalamus was abolished by constant light but was not affected by pinealectomy. Nor did pinealectomy affect hypothalamic TRH content, pituitary content of thyroid-stimulating hormone (TSH) or prolactin; serum levels of (TSH), triiodothyronine (T3), or thyroxine (T4), or serum free-thyroxine index; or free-triiodothyronine index. Melatonin did not affect TSH or prolactin release from the anterior pituitary or TRH release from the hypothalamus in vitro. Isoproterenol did not affect the TRH content of pineal glands in vitro; nor did TRH or T3 affect basal or stimulated activities of serotonin N-acetyltransferase, the presumed controlling enzyme in melatonin production. We found no evidence for significant interactions between the pineal gland and the hypothalamus-pituitary-thyroid axis.
Effects of starvation and diabetes on protein synthesis in lung.
Authors: Rannels D E , Sahms R H , Watkins C A
Published: December 2017

Metabolism of lung proteins was investigated in rats starved 3 days or made diabetic with streptozotocin. Body weight was below normal in both groups, but lung weight decreased only in starved animals. Total lung protein and RNA (mg/lung) decreased during starvation and diabetes. Protein concentration (mg/g) was unchanged in either group of animals; RNA concentration decreased only during starvation. Protein synthesis, estimated in lungs perfused in situ, was reduced 22% in starvation, but remained unchanged in diabetes. Inhibition of protein synthesis was accounted for by loss of RNA. Ribosomal profiles were unchanged by starvation, suggesting an unaltered relationship between rates of peptide-chain initiation and elongation in vivo. Activity of an eIF-2-like initiation factor decreased during starvation in proportion to the loss of RNA. In diabetes, factor activity remained normal. Thus, starvation but not streptozotocin-induced diabetes, reduced the capacity of the lung to synthesize protein. No evidence for reduced efficiency of synthesis was observed.
Effect of bethanechol, gastrin I, or cholecystokinin on myoelectrical activity.
Authors: Snape W J , Cohen S
Published: December 2017

The purpose of this study was to determine the effect of bethanechol, gastrin I, or the octapeptide of cholecystokinin (CCK-OP) on the smooth muscle of the isolated cat colon. Myoelectrical activity was recorded with monopolar glass-pore electrodes. Slow-wave frequency was 5.9 +/- 0.2 cycles/min during the basal period. Slow waves were generally coupled during the control period and the apparent propagation velocity was predominantly aborad at a velocity of 3.8 +/- 0.4 mm/s. Spike activity was superimposed on 11.9 +/- 1.5% of the slow waves during the control period. Bethanechol stimulated a dose-dependent increase in colonic spike activity, with a threshold concentration of 10(-7) M. Bethanechol did not alter the congruence of the colonic slow-wave frequency at any concentration. Gastrin I or CCK-OP increased colonic spike activity. The threshold concentrations for gastrin I and CCK-OP were 2 X 10(-11) M and 4 x 10(-11) M, respectively. Unlike bethanechol, gastrin I (2 X 10(-9) M - 2 X 10(-8) M) and CCK-OP (4 X 10(-9) - 4 X 10(-8) M) altered slow-wave frequency and decreased slow-wave congruence. These studies suggest that 1) bethanechol, gastrin I, or CCK-OP increases colonic spike activity, and 2) only gastrin I or CCK-OP alters the slow-wave frequency of colonic muscle. Thus neurohumoral substances may act independently on colonic spike activity and colonic slow-wave frequency.
Effect of altered intestinal water transport on rabbit ileal blood flow.
Authors: Donowitz M , Wicklein D , Reynolds D G , Hynes R A , Charney A N , Zinner M J
Published: December 2017

A method is described for measuring ileal blood flow in the anesthetized (pentobarbital sodium) rabbit by the intraventricular injection of microspheres (15 micrometer) labeled with cerium-141 or chromium-51; with this method the amount of labeled microspheres lodging in the tissue is proportional to the blood flow. Blood flow to the ileal mucosa plus submucosa could be separated from flow to the ileal muscularis propria plus serosa by this technique. Simultaneous and sequential injections of radiolabeled microspheres gave similar measurements of ileal blood flow and did not affect ileal water absorption. Increasing ileal water absorption by treatment with the glucocorticoid methylprednisolone (3 mg/100 g per day for 3 days) increased blood flow to both compartments of the ileum and also to the colon, liver, and kidneys; methylprednisolone treatment did not alter blood flow when studies were performed before the methylprednisolone-induced increase in ileal water absorption had occurred. In contrast, intestinal secretagogues that induced both active ileal secretion (purified cholera toxin and serotonin) and passive ileal secretion (hypertonic mannitol) did not affect ileal blood flow. These studies indicate that increased ileal water absorption is associated with increased ileal blood flow, whereas intestinal secretion is not necessarily associated with an alteration in ileal blood flow.
Effect of gastrin I and gastrin II on canine bile flow.
Authors: Kaminski D L , Deshpande Y G
Published: December 2017

The role of gastrin in the hormonal control of canine hepatic bile flow was evaluated. Because of the importance of the presence of sulfation of the carboxyl terminal peptide in the function of other cholecystokinetic hormones and peptides in the biliary tract, the choleretic properties of sulfated gastrin II were compared to the choleretic properties of nonsulfated gastrin I. Exogenous administration of gastrin I and II to dogs with chronic bile fistulas demonstrated that gastrin II, but not I, significantly increased hepatic bile flow. Chemical stimulation of the release of endogenous gastrin in dogs with denervated antral pouches did not increase hepatic bile flow, whereas a choleresis resulted when the innervated antrum was stimulated. Serum gastrin values obtained during the infusion of gastrin II at doses that produced a choleresis resulted in serum gastrin values that were greater than those produced by a more physiological stimulus, such as chemical antral stimulation. The results of this study suggest that only the sulfated gastrin II, not gastrin I, is a choleretic agent in dogs and only at pharmacological, not physiological doses.