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At least 685 records · Page 38Linked to original sources
PubMed1990

IL-1 secretion by macrophages. Enhancement of IL-1 secretion and processing by calcium ionophores.

In the present study we have demonstrated that the murine IL-1 alpha precursor lacks a cleavable signal sequence and does not undergo cotranslational translocation across microsomal membranes in vitro. Culture supernatants of the murine macrophage cell line, P388D, or from normal peritoneal macrophages collected within 0.5 to 3 h after stimulation contained the 33,000 m.w. precursor as the predominant form of IL-1 alpha. Over an 18-h period, the level of low m.w. IL-1 alpha increased as the secreted precursor was processed by extracellular and/or cell surface-associated proteolytic enzymes. The calcium ionophores A23187 and ionomycin were found to dramatically enhance the release and processing of murine and human IL-1. The rapid release of IL-1 in response to a change in the intracellular level of calcium does not appear to be caused by release of a membrane-bound form of the protein, nor is there evidence that IL-1 is packaged and released from cytoskeletal associated secretory granules. In marked contrast, calcium ionophores do not induce secretion of IL-1 from a nonmacrophage cell line that synthesizes but does not normally secrete IL-1. Our results suggest that activated macrophages possess a novel processing independent, possibly calcium-dependent, mechanism that allows for the release of the precursor forms of IL-1 alpha and IL-1 beta.

Animals↗
PubMed1990

[Secretion of plasminogen activators and their inhibitors in corneal fibroblasts. Modification of this secretion in Schnyder's lens corneal dystrophy].

In this study, we have shown that the secretion of plasminogen activators (PA) by corneal fibroblasts from Schnyder dystrophy is much lower than that secreted by normal corneal fibroblasts. This defective secretion of PA was noted both in the supernatant of cell culture and on the cell surface. This anomaly is found in cultured fibroblasts and therefore is not related to environment modification. Since PA was implicated in remodeling of extracellular matrix, we hypothesized that this anomaly should be responsible for the corneal dystrophy.

Cells, Cultured↗
PubMed1990

Secretion of endogenous lithium in teleost kidneys as a probable reflection of Na+ and water secretion in their renal proximal tubules.

Unlike mammals with renal reabsorption of lithium (Li+), in freshwater and, particularly, marine teleosts net secretion of this trace element by kidneys was discovered. The ratio of Li+ natural concentration (measured by mass spectrometric isotope dilution technique) in urine to that in blood plasma--(U/P)Li--lies in the range 2-6 in the freshwater species and between 5 and 14 in marine species, i.e. as a rule it is essentially higher than the inulin concentration index (U/P)In. It is supposed that the in vivo observed lithium net secretion in whole kidney reflects and quantitatively estimates Na+ and water secretion in renal proximal tubules of teleosts.

Animals↗
PubMed1986

[Comparison of the secretion of growth hormone during sleep and after pharmacologic stimulation. Results of treatment with hGH in cases of dissociated secretions].

Maximal response (peak) of growth hormone (GH) after conventional pharmacologic stimuli have been compared to maximal level reached during sleep in 215 children (123 prepubertal, 92 early pubertal) (group A). A weak correlation (r = 0.37, p less than 0.001) was observed. Five sub-groups of patients could be distinguished according to their GH pharmacologic or sleep peaks: 115 with normal secretion in both cases (I), 10 with complete deficiency (II), 27 with partial deficiency (III), 34 with normal GH sleep secretion and low responses to stimuli (IV) and 29 with the inverse situation (V). A second group (B) of 30 very short children (17 prepubertal and 13 early pubertal) had borderline or variable responses after several pharmacologic stimuli. hGH therapy was done to every patients of sub-group A II, 12 of sub-group A III, 9 of subgroup A IV, 5 of sub-group A V and every one of group B. A sharp rise of growth rate has been obtained with hGH in every patients of sub-groups A II and A III, in 10 out of 14 patients of sub-groups A IV and A V and in almost all patients of group B. A sharp rise of growth rate has been obtained with hGH in every patients of sub-groups A II and A III, in 10 out of 14 patients of sub-groups A IV and A V and in almost all patients of group B. hGH effect in the three last kinds of patients, with atypical GH secretion, was better in those who were in early puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1975

Immunological studies on bronchial secretion. II. Antibodies against bronchial secretion in systemic lupus erythematosus and asthmatic patients.

Bronchial secretion was tested by double gel-diffusion with sera from 100 asthmatic patients, 72 systemic lupus erythematosus patients, 29 patients with other diseases and 31 normal individuals. Positive gel-diffusion reactions were observed only in the sera from two patients with S.L.E. Sera from 100 asthmatic patients, 29 non-allergic patients and 31 normal individuals, tested with bronchial secretion by the passive haemagglutination and inhibition test, showed only three positive reactions with sera from asthmatic patients. Two problems were discussed: the immunological relationship between antigenic determinants found in the sputum and serum in S.L.E. patients; and the possibility that the bronchial secretion being reabsorbed might act as an auto-antigen.

Antibodies↗
PubMed1984

[Effect of a short-term protein-free diet on endogenous nitrogen secretion: exocrine pancreas secretion in the pig].

A protein-free diet is often used in animal experimentation to estimate the amount of total endogenous nitrogen secreted by the organism. To test the validity of this technique, we carried out a study on pigs describing the short-term (8-day) effect of a protein-free diet on exocrine pancreas nitrogen secretion; this nitrogen was considered as representative of total endogenous nitrogen. After 11 pigs had been adapted to a balanced diet (14% protein), they were chronically fistulated in the pancreatic duct and duodenum. Pancreatic secretion and its various parameters (volume, total protein and chymotrypsin, trypsin, amylase and lipase activities) were measured over a first experimental period of 4 days, during which the pigs continued to receive the balanced diet, and over a second experimental period of 8 days during which they were given a protein-free diet. The results show that the amount of pancreatic protein did not change during the period the protein-free diet was given. After 2 days, chymotrypsin specific activity dropped, while amylase and lipase specific activities decreased little and slowly after 6 days. However, for short-term experiments, the protein-free diet proved to be an adequate technique for determining the production of total endogenous nitrogen in the digestion tract.

Amino Acids↗
PubMed1982

A continuous, spectroscopic analysis of the kinetics of elastase secretion by neutrophils. The dependence of secretion upon receptor occupancy.

We have developed a continuous spectroscopic method to analyze the kinetics of elastase secretion by human neutrophils. We have used the elastase-specific substrate methylsuccinylalanylalanylprolylvalylmethylcoumarin amide (Castillo, M. J., Nakajima, K., Zimmerman, J., and Powers, J. C. (1979) Anal. Biochem. 99, 53-64), which liberates the fluorophore, aminomethylcoumarin, when cleaved by elastase. We find that secretion of elastase in cytochalasin B-treated cells is initiated within approximately 5 s of exposure of the cells to the fluoresceinated chemotactic peptide stimulus, N-formyl-norleucylleucylphenylalanylnorleucyltyrosyllysine-fluorescein, and that secretion is completed within 30 s. The kinetics of this response is only slightly dependent on the concentration of the stimulus. Up to 100% (approximately 0.5 pg/neutrophil) of the elastase can be released in a dose-dependent manner by stimulated cells. We have also used this fluoresceinated stimulus and an antibody to fluorescein (Sklar, L. A., Oades, Z. G., Jesaitis, A. J., Painter, R. G., and Cochrane, C. G. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 7540-7544) to probe the temporal relationship between the binding of stimulus to the receptors and the cellular response. We find that the entire response is elicited by the binding which occurs within the first 15 s after the addition of stimulus, regardless of the dose. We estimate that an occupancy of no more than 20% of the cellular receptors for the stimulus is required to evoke the optimal response.

Cytochalasin B↗
PubMedDate not supplied

[Effect of chlorpromazine on adrenal secretion of corticosterone and pituitary secretion of prolactin].

1. The authors studied, in adult male and female rats the effect of one or repeated injections of chlorpromazine on adrenal secretion of corticosterone and pituitary secretion of prolactin. 2. Injections of chlorpromazine increased plasma corticosterone, plasma and pituitary prolactin. 3. The discussion of the results was correlated to the brain catecholamines postulated to be neurotransmitters involved in the control of corticotropin and prolactin pituitary secretion.

Adrenal Cortex↗
PubMed1993

Effect of secretion on vagal stimulation-evoked exocrine pancreatic secretion in the rat.

The effect of secretin on nerve-mediated pancreatic juice secretion in the anaesthetized rat has been studied. Vagotomy caused a significant reduction in the rate of pancreatic juice flow, total protein output and amylase secretion being compared to control values prior to vagotomy. Both secretin (intravenous infusion 10(-10) mol/kg body weight/h) and electrical stimulation of the vagus nerves (4 V, 2 ms, 20 Hz) caused marked increases in flow, total protein output and amylase output. Pretreatment of rats with atropine (0.1 mg/kg body weight) abolished the electrical stimulation-evoked secretion. However, simultaneous intravenous infusion of secretin and electrical stimulation did not yield either a clear additive response or a potentiation of secretory responses.

Amylases↗
PubMed1977

Blocking of protein pancreatic secretion by maximal secretion infusion in the dog.

In conscious chronic gastric and pancreatic fistula dogs (Thomas cannula), secretin was perfused for three hours with a submaximal (GIH, 1.0 C.U./kg.) and a maximal dose (GIH, 8.0 c.u./kg.), according to the following schedule: 1. First hour submaximal stimulus; 2. second hour maximal stimulus; 3. third hour submaximal stimulus. The alkaline and protein components of pancreatic secretion were analyzed in 20-minute sample collections thoughout the three hours. The same protocol was followed in anesthetized dogs subjected to a mind line laparotomy. A biopsy of the pancreatic gland was taken before (control) and at the end of each perfused dose. The secretion showed a significant increase of protein concentration and output when passing from the maximal to the last submaximal secretin perfusion dose. These findings correlated well with the piling up of zymogen and prozymogen granules in the apical zone of the acinar cells during maximal secretin perfusion, with their subsequent discharge into the acinar lumen upon abrupt reversal to the initial secretin submaximal dose. The study confirms that secretin influences pancreatic protein secretion and indicates in addition, that pharmacologic doses of the hormone, have the capacity to block acinar cell zymogen granule release.

Animals↗
PubMed2006

Impaired insulin secretion in vivo but enhanced insulin secretion from isolated islets in pancreatic beta cell-specific vascular endothelial growth factor-A knock-out mice.

AIMS/HYPOTHESIS: Endothelial cells are considered to be essential for normal pancreatic beta cell function. However, there have been no reports showing their importance for beta cell function. MATERIALS AND METHODS: Using mice with disrupted vascular endothelial growth factor-A gene specifically in beta cells, we investigated the relation between islet vascular structure and beta cell function. RESULTS: Mice with disrupted vascular endothelial growth factor-A gene specifically in beta cells had reduced islet vascular density with impaired formation of endothelial fenestration. While their fasting glucose and body weight were comparable with control mice, their glucose- and tolbutamide-induced rapid insulin release were impaired, thus resulting in glucose intolerance. On the other hand, glucose and KCl enhanced the levels of insulin secreted from islets isolated from these mice. In addition, the production of soluble N-ethylmaleimide-sensitive factor attachment protein receptors in the islets was increased. Insulin content and expression of insulin I and pancreas duodenum homeobox 1 mRNA in the islets were also increased. CONCLUSIONS/INTERPRETATION: Our results indicate that an abnormal quality and quantity of blood vessels due to reduced expression of vascular endothelial growth factor-A in beta cells could be a cause of impaired insulin secretion without impairment of beta cell function.

Animals↗
PubMed1980

Vasoactive intestinal peptide inhibition of stimulated gastric secretion. I. Inhibition of meat-stimulated gastric secretion.

In an effort to demonstrate a physiologic role of vasoactive intestinal peptide, awake dogs with either Heidenhain pouches or Thiry-Vella loops and duodenal cannulas with duodenoduodenostomies to prevent obstruction were stimulated with meat meals given by mouth and infusions of various substances given intraduodenally, including hypertonic saline solution or 0.16 normal hydrochloric acid. Stimulated Heidenhain pouch secretion was significantly inhibited by concomitant intraduodenal administration of hydrochloric acid. Plasma vasoactive intestinal polypeptide was highest in the animals who received hydrochloric acid intraduodenally among all the intraduodenal stimuli. These findings support a role for vasoactive intestinal polypeptide as a physiologic inhibitor of gastric secretion, at least in dogs.

Animals↗
PubMed1983

Expressing a human proinsulin cDNA in a mouse ACTH-secreting cell. Intracellular storage, proteolytic processing, and secretion on stimulation.

The AtT-20 cell line, derived from the mouse anterior pituitary, synthesizes an adrenocorticotropic hormone (ACTH) precursor, proteolytically processes it to mature ACTH, stores it in secretory granules, and releases mature ACTH on stimulation with a secretagogue. A cDNA for human proinsulin inserted downstream from the SV40 early promoter in an SV40-pBR322 recombinant vector was introduced into AtT-20 cells. The stably transformed cell line, AtT-20ins4b/1, stores immunoreactive insulin, proteolytically processes proinsulin to smaller fragments, and on stimulation with secretagogues releases insulin-like material, not proinsulin, into the medium. Similarly transformed fibroblast L-cells secrete only proinsulin; they do not store it, and their secretion rate is unaffected by secretagogues. The transport mechanism for precursor ACTH thus appears to recognize other prohormones.

Adrenocorticotropic Hormone↗
PubMed1997

RIN14B: a pancreatic delta-cell line that maintains functional ATP-dependent K+ channels and capability to secrete insulin under conditions where it no longer secretes somatostatin.

The delta-cell line RIN14B was characterized with regard to ATP-regulated K+ (K(ATP)) channel activity and hormone release. By applying the patch-clamp technique, dose-response curves for ATP and the sulfonylurea tolbutamide were obtained in inside-out patches. The concentration causing half-maximal K(ATP) channel inhibition was found to be 23.7 and 27.6 microM for ATP and tolbutamide, respectively. ADP and diazoxide stimulated K(ATP) channel activity, an effect dependent on the presence of intracellular Mg2+. The stimulatory effect of diazoxide also required the presence of ATP. The kinetic properties of the K(ATP) channel were analysed in the presence of ATP, a combination of ADP and ATP and in nucleotide-free solutions. The distribution of K(ATP) channel open time could be described by a single exponential function with a time constant of approximately 30 ms in nucleotide-free and in ATP-containing solutions. The presence of both ATP and ADP resulted in the appearance of an additional time constant of > 150 ms. Single-channel unitary current-voltage (i-V) relation was characterised for the K((ATP) channel present in RIN14B cells. The slope conductance, measured at the reversal potential was found to be 19.1 +/- 2.4 pS. The permeability for K+ ions was calculated to be 0.31 x 10(-13) cm3 x s(-1). We have not been able to confirm the somatostatin releasing profile of the RIN14B cells using radioimmunoassays, nor could we find positive somatostatin stain with immunocytochemical techniques. We conclude that the RIN14B cell line, previously characterized as a somatostatin-secreting cell line, contains K(ATP) channels with properties closely resembling the K(ATP) channel described in the pancreatic beta-cell. However, the cell line appears to have dedifferentiated with regard to the ability to secrete somatostatin, maintaining the highly differentiated function of both insulin biosynthesis and exocytosis.

Adenosine Diphosphate↗
PubMed1992

The effect of the somatostatin analogue octreotide on growth hormone secretion in insulin-dependent diabetics without residual insulin secretion.

Growth hormone (GH) hypersecretion is well documented in insulin-dependent diabetes mellitus (IDDM). Somatostatin inhibits GH in acromegalics and healthy subjects although data on its inhibitory effects on high GH levels in IDDM patients are controversial. The effect of treatment with the somatostatin analogue octreotide ("Sandostatin") on GH secretion, IGF1 levels and metabolic control was investigated in insulin-dependent diabetics. Growth hormone and blood glucose were measured at hourly intervals whilst IGF-I was measured every 6 hours during the 24-h period before and after 7 days' treatment with octreotide (200 micrograms subcutaneously three times daily) in 10 C-peptide negative diabetics. Octreotide significantly reduced mean 24 h GH profile (7.2 +/- 0.7 mU/L before; 5.2 +/- 0.5 mU/L on octreotide, p less than 0.01), IGF-I levels (0.62 +/- 0.06 before; 0.47 +/- 0.05 on octreotide, p less than 0.005) mean 24 h blood glucose (14.4 +/- 0.5 mmol/L before; 12.6 +/- 0.4 mmol/L on octreotide, p less than 0.001) and daily insulin requirements (44.8 +/- 3.0 IU before; 37.2 +/- 3.0 IU on octreotide, p less than 0.02). The shape of 24 h GH profile curve changed significantly on octreotide treatment (p less than 0.05) when it consisted of three nadirs and three peaks closely linked with the time of octreotide administration. Moderate (abdominal discomfort) to severe hypoglycaemia) transient side effects have been observed in all treated patients. The results of this study showed that short-term treatment with octreotide given s. c. every eight hours modulates the pattern of GH secretion in C-peptide negative insulin-dependent patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Studies on gastric digestion of protein and carbohydrate, gastric secretion and exocrine pancreatic secretion in the growing pig.

Six pigs, initially of 35 kg mean live weight, were each fitted with a re-entrant cannula. This was formed on either side of a short pouch of duodenum into which the pancreatic duct opened and which contained a simple cannula linked to the centre of the re-entrant cannula. Each pig received two diets: diet A was based on wheat starch, sucrose and casein, while diet B was based on barley and soya-bean meal. The diets were given in equal amounts at 12 h intervals. Digesta and pancreatic juice were collected continuously during three 12 h periods for each pig on each diet. Mean duodenal output: dietary intake values for diets A and B respectively were: digesta 1.80, 2.86; dry matter 1.05, 1.03; nitrogen 1.05, 1.06; trichloroacetic acid (TCA)-soluble N 7.69, 9.10; glucose 0.97, 0.89. For diet A the proportion of TCA-soluble N in total N rose from 13 to 50% during 12 h, while it was approximately 50% throughout 12 h for diet B. Mean total pepsin (EC 3.4.23.1) activities (units/24 h) were 760449 (diet A) and 1 466 571 (diet B). Salivary and gastric secretions were calculated to be approximately 4 and 8 kg/24 h for diets A and B respectively. Mean flows in pancreatic juice (g/24 h) for diets A and B respectively were: juice 1204, 2182; protein 10.94, 12.10; N 1.98, 2.14; ash 9.46, 17.31; sodium 3.88, 6.91; potassium 0.23, 0.54; calcium 0.031, 0.046; phosphorus 0.024, 0.026. Mean total enzyme activities (units x 10(-3)/24 h) for diets A and B respectively were: trypsin (EC 3.4.21.4) 138, 114; chymotrypsin (EC 3.4.21.1) 84, 84; carboxypeptidase A (EC 3.4.2.1) 5, 4; carboxypeptidase B (EC 3.4.2.2) 15, 17; amylase (EC 3.2.1.1) 1061, 981. It was calculated that the minimum amount of endogenous N from saliva and gastric secretion was 0.3-0.6 g in 24 h. This assumes no absorption of N occurred anterior to the duodenal cannula.

Animals↗
PubMed1996

Betacellulin and activin A coordinately convert amylase-secreting pancreatic AR42J cells into insulin-secreting cells.

Rat pancreatic AR42J cells possess exocrine and neuroendocrine properties. Activin A induces morphological changes and converts them into neuron-like cells. In activin-treated cells, mRNA for pancreatic polypeptide (PP) but not that for either insulin or glucagon was detected by reverse transcription-PCR. About 25% of the cells were stained by anti-PP antibody. When AR42J cells were incubated with betacellulin, a small portion of the cells were stained positively with antiinsulin and anti-PP antibodies. The effect of betacellulin was dose dependent, being maximal at 2 nM. Approximately 4% of the cells became insulin positive at this concentration, and mRNAs for insulin and PP were detected. When AR42J cells were incubated with a combination of betacellulin and activin A, approximately 10% of the cells became insulin positive. Morphologically, the insulin-positive cells were composed of two types of cells: neuron-like and round-shaped cells. Immunoreactive PP was found in the latter type of cells. The mRNAs for insulin, PP, glucose transporter 2, and glucokinase, but not glucagon, were detected. Depolarizing concentration of potassium, tolbutamide, carbachol, and glucagon-like peptide-1 stimulated the release of immunoreactive insulin. These results indicate that betacellulin and activin A convert amylase-secreting AR42J cells into cells secreting insulin. AR42J cells provide a model system to study the formation of pancreatic endocrine cells.

Activins↗
PubMed1978

L-Leucine-induced secretion of glucagon and insulin, and the "off-response" to L-leucine in vitro. I. Characterization of the dynamics of secretion.

The effects of L-leucine, D-leucine, and L-isoleucine upon the secretion of glucagon and insulin were investigated using the isolated, perfused rat pancreas. All experiments were conducted in the presence of 5.6 mM D-glucose. Ten-minute perfusions of 2, 5, and 10 mM L-leucine induced the release of glucagon and insulin in a dose-related manner. The removal of L-leucine was followed by renewed release of insulin ("off-response") but not of glucagon. The magnitude of the off-response was greater when L-leucine was perfused over longer periods. L-Isoleucine evoked the release of both glucagon and insulin. When L-leucine was administered during perfusion of L-isoleucine, L-leucine-induced release of glucagon was inhibited, that of insulin was augmented, and the insulin off-response prevailed. When the perfusion of L-leucine immediately preceded that of L-isoleucine, L-isoleucine-induced release of glucagon was abolished and that of insulin was augmented. D-Leucine evoked the release of glucagon but not of insulin, and no off-response occurred. When the perfusion of D-leucine followed that of L-leucine, D-leucine-induced glucagon release was inhibited; the insulin off-response to L-leucine was not altered. We reached the following conclusions. 1) Glucagon release induced by L-leucine, D-leucine, or L-isoleucine is likely to be related to the occupancy by these analogous amino acids of transport and/or receptor sites which they share. 2) The insulin off response to L-leucine seems to be evoked by events which take place during the period of administration of L-leucine; these events are not likely to be the release of insulin that occurs during perfusion of L-leucine or the transport of L-leucine into or out of the beta cell. 3) Structurally or chemically similar compounds which are secretagogues both for glucagon and insulin affect the release of these hormones in different ways; these differences are likely to be due to dissimilar mechanisms governing the secretion of the two hormones.

Animals↗