scholarly journals Tryptophan and the control of plasma glucose concentrations in the rat

1977 ◽  
Vol 168 (3) ◽  
pp. 495-506 ◽  
Author(s):  
S A Smith ◽  
C I Pogson
Keyword(s):  
Adrenal Glands ◽  
Experimental Diabetes ◽  
Plasma Concentrations ◽  
Hypoglycaemic Effect ◽  
Esterified Fatty Acids ◽  
Tryptophan Metabolites ◽  
The Central Nervous System ◽  
Concentration Changes ◽  
Beta Hydroxybutyrate ◽  
Hydrazinopropionic Acid

1. Injection of L-tryptophan (750 mg/kg body wt.) led to pronounced hypoglycaemia in fed and 48 h-starved rats. 2. The hypoglycaemic effect is blocked by pretreament with p-chlorophenylalanine, compound MK-486 [Carbidopa: L-alpha-(3,4-dihydroxybenzyl)-alpha-hydrazinopropionic acid monohydrate] or methysergide, and potentiated by pargyline. 3. 5-Hydroxy-L-tryptophan is more potent and induces a more rapid hypoglycaemia than does tryptophan. Other tryptophan metabolites were not associated with hypoglycaemia. 4. Adrenalectomy increases, and acute experimental diabetes strongly decreases, the sensitivity of rats to tryptophan induction of hypoglycaemia. Diabetic animals were also insensitive to 5-hydroxytryptophan. 5. Metabolite concentration changes in the livers from tryptophan-treated 48h-starved and diabetic animals were consistent with a rapid inhibition of gluconeogenesis. This did not correlate with the hypoglycaemic response. 6. Tryptophan treatment was associated with a significant increase in the plasma [beta-hydroxybutyrate]/[acetoacetate] ratio; there were no changes in the plasma concentrations of urea, triacyglycerol, non-esterified fatty acids and glycerol. 7. These observations suggest that the hypoglycaemic action of tryptophan is mediated through formation of intracellular 5-hydroxytryptamine, and is unrelated to the inhibition of gluconeogenesis. It is unlikely that this increased synthesis of 5-hydroxytryptamine involves directly either the adrenal glands or the central nervous system.

scholarly journals Insulin resistance of hind-limb tissues in vivo in lactating sheep

1990 ◽  
Vol 270 (3) ◽  
pp. 783-786 ◽  
Author(s):  
R G Vernon ◽  
A Faulkner ◽  
W W Hay ◽  
D T Calvert ◽  
D J Flint
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mammary Gland ◽  
Hind Limb ◽  
Insulin Infusion ◽  
Plasma Concentrations ◽  
Plasma Insulin Concentration ◽  
Esterified Fatty Acids ◽  
Beta Hydroxybutyrate

1. The effects of varying the plasma insulin concentration by infusion while maintaining euglycaemia by infusion of glucose on nutrient arterio-venous differences across the hind-limb and mammary gland in lactating and non-lactating sheep were investigated. 2. Insulin infusion increased the glucose arterio-venous difference across the hind-limb; this effect of insulin was decreased by lactation, suggesting that lactation induces insulin resistance in skeletal muscle. 3. Lactation increased but insulin infusion decreased the plasma concentrations of acetate, beta-hydroxybutyrate and non-esterified fatty acids. 4. Insulin infusion decreased the arterio-venous differences of acetate and hydroxybutyrate across the hind-limb; this effect of insulin is probably indirect, resulting from the decrease in plasma concentrations of these metabolites. 5. Infusion of insulin had no effect on the glucose arterio-venous difference across the mammary gland, but did decrease the oxygen arterio-venous difference. 6. The results suggest that lactation results in insulin resistance in skeletal muscle, at least with respect to glucose utilization; this should facilitate the preferential utilization of glucose by the mammary gland.

Modeling Studies of the Dynamic Control of Hepatic Glucose Balance

1975 ◽  
Vol 97 (3) ◽  
pp. 266-275
Author(s):  
R. N. Bergman ◽  
M. El Refai
Keyword(s):  
Central Nervous System ◽  
Dynamic Control ◽  
Plasma Concentrations ◽  
Glycogen Metabolism ◽  
Hepatic Glycogen ◽  
Simulation Studies ◽  
Biochemical Effects ◽  
Hepatic Glucose ◽  
Large Fluctuations ◽  
The Central Nervous System

The survival of mammals is dependent upon a relatively constant, adequate supply of glucose to the central nervous system, despite large fluctuations in the amount of food available. When food is abundant, the liver stores ingested carbohydrate as glycogen, and during fasts, the stored glycogen is released at a precisely regulated rate to maintain the blood glucose level. The rates of storage and release of carbohydrate by the liver are determined by the plasma concentrations of several bloodborne signals; most important are the concentrations of glucose, and the hormones insulin and glucagon. To understand the complex control relationships of these three signals as they affect the liver, their individual dynamic influences have been determined experimentally, and they have been integrated by means of a computer simulation of the pathways of hepatic glycogen metabolism. The simulation studies have led to specific hypotheses about the biochemical effects of glucose and insulin on the liver. The simulation studies have also led to the conclusion that glucose exerts a rapid moment-to-moment influence of glucose on the rate of uptake of glucose by the liver. Insulin, however, by exerting a slower influence on the sensitivity of the liver to glucose, is very effective in “optimizing” the amount of glycogen which the liver stores food during food intake. Thus, integrated experimental and simulation studies can lead to a view of a physiological regulating system which does not emerge from either approach used alone.

Glucocorticoids alter fever and IL-6 responses to psychological stress and to lipopolysaccharide

1993 ◽  
Vol 264 (5) ◽  
pp. R1010-R1016 ◽  
Author(s):  
L. E. Morrow ◽  
J. L. McClellan ◽  
C. A. Conn ◽  
M. J. Kluger
Keyword(s):  
Tumor Necrosis Factor ◽  
Open Field ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Adrenal Glands ◽  
Plasma Concentrations ◽  
Necrosis Factor Alpha ◽  
Inhibitory Feedback ◽  
Factor Alpha ◽  
Necrosis Factor

The purpose of this study was to determine whether glucocorticoids exert inhibitory feedback on lipopolysaccharide (LPS)-induced fever, stress-induced fever (exposure to an open field), and plasma concentrations of interleukin-6 (IL-6)-like and tumor necrosis factor-alpha (TNF)-like activity in biotelemetered rats. Injections of LPS (50 micrograms/kg) or exposure to an open field (30 min) led to significantly higher fevers in adrenalectomized (ADX) rats than in sham-ADX rats. To test the hypothesis that higher fevers were specifically the result of an absence of glucocorticoids, the glucocorticoid antagonist RU 38486 (20 mg/kg) was administered orally to rats with intact adrenal glands. The RU 38486-treated rats had higher plasma concentrations of IL-6-like activity and developed significantly higher fevers than did vehicle-treated rats. Rats injected intracerebroventricularly with 10 ng RU 38486 also developed higher fevers. Other ADX animals were implanted subcutaneously with replacement corticosterone pellets before exposure to an open field or injection with LPS. In response to an open field or injection with LPS, ADX animals implanted with replacement pellets that mimic plasma concentrations of corticosterone observed in stressed animals (100-mg pellets) developed fevers that were significantly lower than those observed in ADX rats given placebo pellets, but that were not different from fevers in sham-ADX rats given placebo pellets. ADX animals implanted with replacement pellets that mimic plasma concentrations of corticosterone observed in unstressed animals (25-mg pellets) developed fevers that were significantly higher than those observed in sham-ADX rats given placebo pellets, but that were not different from fevers in ADX rats given placebo pellets.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of adrenomedullary function in suckling rats: Effects of high doses of thyroxine and cortisol

1990 ◽  
Vol 123 (1) ◽  
pp. 100-107
Author(s):  
L. Goya ◽  
C. Aláez ◽  
A. M. Pascual-Leone
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adrenal Glands ◽  
Normal Development ◽  
Insulin Administration ◽  
Newborn Rats ◽  
Short Intervals ◽  
Slowing Down ◽  
The Central Nervous System ◽  
High Doses

Abstract. The development of epinephrine, norephinephrine, and total catecholamine secretion in plasma and andrenal glands was studied in newborn rats at short intervals: at day 2, 4, 6, 8, 10, 12 and 23. The increase in the plasma level of epinephrine represents a maturation of the secretion of the adrenal medulla. The increase in plasma of epinephrine and norepinephrine and the content of catecholamines in the adrenal glands of both normal animals and those treated with either high doses of T4 or cortisol at birth suggest a slowing down of the normal development of epinephrine secretion. This was confirmed by inducing hypoglycemia in these three groups of animals by a 20-h fast or by insulin administration (0.1436 μmol/kg). We conclude that both high doses of T4 and cortisol administered at birth seem to retard the development of the autonomic nervous system similar to the effect on the central nervous system.

Hormonal-sympathetic interactions in long-term regulation of arterial pressure: an hypothesis

1995 ◽  
Vol 268 (6) ◽  
pp. R1343-R1358 ◽  
Author(s):  
V. L. Brooks ◽  
J. W. Osborn
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Arterial Pressure ◽  
Plasma Concentrations ◽  
Circumventricular Organs ◽  
Feedback Signal ◽  
Salt Loading ◽  
Alternate Model ◽  
The Central Nervous System

The importance of the sympathetic nervous system in short-term regulation of arterial pressure is well accepted. However, the question of whether neural systems participate in long-term control of pressure has been debated for decades and remains unresolved. The principal argument against such a control system is that arterial baroreceptors adapt to sustained changes in arterial pressure. In addition, denervation of baroreceptors has minimal to no effect on basal levels of arterial pressure chronically. This argument assumes, however, that baroreceptors provide the primary chronic feedback signal to the central nervous system. An alternate model is proposed in which circulating hormones, primarily arginine vasopressin and angiotensin II, provide a long-term afferent signal to the central nervous system via binding to specific receptors in central sites lacking a blood-brain barrier (circumventricular organs). Studies suggest that the release of the hormones and the sympathetic response to alterations in their plasma concentrations are nonadaptive but may be gated by baroreceptor input. Evidence that this "hormonal-sympathetic reflex" model may explain the long-term alterations in sympathetic activity in response to chronic salt depletion and salt loading as well as congestive heart failure is presented. Finally, the role of an impaired hormonal sympathetic reflex in hypertension, specifically salt-dependent hypertension, is discussed.

Intestinal growth is associated with elevated levels of glucagon-like peptide 2 in diabetic rats

1997 ◽  
Vol 273 (4) ◽  
pp. E815-E820 ◽  
Author(s):  
Kirk D. Fischer ◽  
Savita Dhanvantari ◽  
Daniel J. Drucker ◽  
Patricia L. Brubaker
Keyword(s):  
Experimental Diabetes ◽  
Plasma Concentrations ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Villus Height ◽  
Intestinal Growth ◽  
Glucagon Like Peptide ◽  
Small Intestinal ◽  
The Relationship ◽  
Intestinal Weight

Glucagon-like peptide 2 (GLP-2) has recently been identified as a novel intestinal growth factor. Because experimental diabetes is associated with bowel growth, we examined the relationship between GLP-2 and intestinal growth in rats made diabetic by streptozotocin (STZ) injection and treated with or without insulin for 3 wk. Ileal concentrations of the intestinal proglucagon-derived peptides, i.e., glicentin + oxyntomodulin, and GLPs 1 and 2, were increased by 57 ± 20% above those of controls in untreated STZ diabetes ( P < 0.05–0.001). Similar increases in plasma concentrations of glicentin + oxyntomodulin (77 ± 15% above controls, P < 0.01) and GLP-2 (91 ± 32% above controls, P < 0.05) were seen in untreated STZ diabetes. Both wet and dry small intestinal weight increased by 74 ± 20% above controls ( P < 0.01) in STZ diabetes, and macromolecular analysis indicated parallel increases in both protein ( P < 0.001) and lipid ( P < 0.05) content. Villus height ( P < 0.001) and crypt depth ( P < 0.01) were also increased in untreated diabetic rat intestine. Insulin therapy prevented the changes in plasma GLP-2 and intestinal mass seen in untreated STZ diabetes. Thus STZ diabetes is associated with both increased production of GLP-2 and enhanced bowel weight, thereby suggesting a role for GLP-2 in diabetes-associated bowel growth.

Peripheral and brain tissue catecholamine content in intact and anti-NGF-treated fetal sheep

1987 ◽  
Vol 252 (1) ◽  
pp. R7-R12 ◽  
Author(s):  
J. A. Schuijers ◽  
D. W. Walker ◽  
C. A. Browne ◽  
G. D. Thorburn
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Gestational Age ◽  
Adrenal Glands ◽  
Matched Control ◽  
Cervical Spinal Cord ◽  
Fetal Sheep ◽  
Catecholamine Content ◽  
The Central Nervous System

Fetal lambs were treated with a single dose of anti-mouse nerve growth factor (anti-NGF) at 80 days gestational age. The catecholamine content of tissues was determined at 135 days gestational age. There was a reduction of either norepinephrine, epinephrine, or both, in the thymus, thyroid, atrium (but not ventricle), lung, liver, kidney, and jejunum when compared with age-matched control fetuses. The spleen, ileum, colon, and the adrenal glands were not affected by anti-NGF. In treated fetuses there was a reduction in catecholamine content of the thalamus, hypothalamus, hippocampus, medulla, cerebellum, and cervical spinal cord. These results show that some tissues are sensitive to, and some are refractory to, the action of anti-NGF at 80 days gestation. Also the results suggest that NGF may play a role in the development of catecholamine-containing neurons within the central nervous system.

scholarly journals Switching to Tenofovir Alafenamide in Elvitegravir-Based Regimens: Pharmacokinetics and Antiviral Activity in Cerebrospinal Fluid

2019 ◽  
Vol 71 (4) ◽  
pp. 982-988 ◽  
Author(s):  
Qing Ma ◽  
Andrew J Ocque ◽  
Gene D Morse ◽  
Chelsea Sanders ◽  
Alina Burgi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Antiviral Activity ◽  
Virologic Failure ◽  
Plasma Concentrations ◽  
Open Label ◽  
Assay Sensitivity ◽  
Once Daily ◽  
Hiv Rna ◽  
The Central Nervous System ◽  
Tenofovir Alafenamide

Abstract Background Tenofovir alafenamide fumarate (TAF) co-formulated with elvitegravir (EVG; E), cobicistat (C), and emtricitabine (F), a recommended antiretroviral regimen, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF) as well as neurocognitive (NC) performance change in participants switching from E/C/F/tenofovir disoproxil fumarate (TDF) to E/C/F/TAF. Methods This was a 24-week, single-arm, open-label study in treatment-experienced adults living with human immunodeficiency virus (HIV). Nine participants switched from E/C/F/TDF (150/150/200/300 mg once daily) to E/C/F/TAF (150/150/200/10 mg once daily) at week 12. CSF and total plasma concentrations of EVG, TDF, TAF, tenofovir (TFV), and HIV RNA levels were measured at baseline and week 24. NC performance was estimated by the Montreal Cognitive Assessment. Results EVG concentrations in CSF and the CSF:plasma ratio remained stable (P = .203) over time. Following the switch, TFV concentrations in CSF and plasma declined (P = .004), although the TFV CSF:plasma ratio increased (P = .004). At week 24, median TAF plasma concentration was 11.05 ng/mL (range, 2.84–147.1 ng/mL) 2 hours postdose but was below assay sensitivity 6 hours after dosing. TAF was below assay sensitivity in all CSF specimens. HIV RNA was ≤40 copies/mL in all CSF and plasma specimens. Three participants (33%) had NC impairment at baseline and 2 (22%) remained impaired at week 24. Conclusions Switch to E/C/F/TAF was associated with reductions in TFV concentrations in CSF but stable EVG concentrations that exceeded the 50% inhibitory concentration for wild-type HIV, suggesting that EVG achieves therapeutic concentrations in the central nervous system. No virologic failure or significant NC changes were detected following the switch. Clinical Trials Registration NCT02251236.

β-Neoendorphin inhibits thyrotrophin secretion in rats

1983 ◽  
Vol 104 (4) ◽  
pp. 437-442 ◽  
Author(s):  
Terunori Mitsuma ◽  
Tsuyoshi Nogimori
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Thyrotrophin Releasing Hormone ◽  
Specific Radioimmunoassay ◽  
Tsh Secretion ◽  
Pretreated Group ◽  
The Central Nervous System ◽  
Tsh Levels

Abstract. The effects of β-neoendorphin on thyrotrophin-releasing hormone (TRH) and thyrotrophin (TSH) secretion in rats were studied. β-neoendorphin (500 μg/kg) was injected iv, and the rats were decapitated serially. TRH, TSH, thyroxine (T4) and 3,3',5-triiodothyronine (T3) were measured by means of a specific radioimmunoassay for each. Hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after β-neoendorphin injection, and plasma concentrations tended to decrease, but not significantly so. Plasma TSH levels decreased significantly in a dose-related manner with a nadir at 40 min. Plasma T4 and T3 levels did not change after the injection. Plasma ir-TRH and TSH responses to cold were significantly inhibited by β-neoendorphin, but the plasma TSH response to TRH was not. Naloxone partially prevented the inhibitory effect of β-neoendorphin on TSH release. In the haloperidol- or 5-hydroxytryptophan-pretreated group, the inhibitory effect of β-neoendorphin on TSH release was prevented, but not in the l-dopa- or para-chlorophenylalanine-pretreated group. These drugs alone did not affect plasma TSH levels at the dose used. These findings suggest that β-neoendorphin acts on the hypothalamus by inhibiting TRH release, which may be modified by amines of the central nervous system.

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