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Mesothelium secretes lamellar bodies in a similar manner to type II pneumocyte secretion of surfactant.

In the early 1970s it was found that a specific lipid-fixing technique of tissue preparation for electron microscopy (tannic acid-glutaraldehyde) preserved and thus unmasked distinctive inclusions in Type II pneumocytes which were called lamellar bodies. This discovery was the first crucial step in demonstrating that lamellar bodies were the storage granules from which alveolar surfactant was secreted. In a previous study a comparison between mesothelium and Type II pneumocytes showed close ultrastructural similarities. In the present investigation of normal peritoneal tissue from man, monkey, rabbit and mouse, following primary tannic acid-glutaraldehyde fixation and modified embedding procedures similar to those used for lung, examination by transmission electron microscopy demonstrated in all mesothelial cells examined, characteristic lamellar structures similar to those described in Type II pneumocytes. Exocytotic extrusion of lamellar bodies from the apical portion of the mesothelial cell, and the presence of lamellar bodies on the cell surface in a manner identical to that found in Type II pneumocytes was also observed. These findings provide compelling evidence that a process of specialized biosynthesis and secretion of phospholipids similar to that established for Type II pneumocytes also occurs in mesothelial cells.

Animals↗

Protein secretion by gram-negative bacteria. Characterization of two membrane proteins required for pullulanase secretion by Escherichia coli K-12.

Pullulanase secretion in Escherichia coli depends on the expression of a MalT-regulated operon called pulC. Characterization of the first two genes of this operon showed that they encode, respectively, a 31,000-Da protein (PulC) and a 70,600-Da protein (PulD) which has a putative signal peptide and that these two proteins are required for pullulanase secretion. The analysis of alkaline phosphatase hybrid proteins generated by TnphoA mutagenesis of pulC and pulD showed that both PulC and PulD contain export signals which can direct the alkaline phosphatase segment of the hybrids across the inner membrane. A representative PulC-PhoA hybrid protein fractionated mainly with the inner membrane upon isopycnic sucrose gradient centrifugation of membrane vesicles. This, together with sequencing data, suggests that PulC is an inner membrane protein. Antibodies raised against a purified PulD-PhoA hybrid protein were used to show that PulD was enriched in low density outer membrane vesicles.

Alkaline Phosphatase↗

Evaluation of the effects induced by four opiate drugs, with different affinities to opioid receptor subtypes, on anterior pituitary LH, TSH, PRL and GH secretion and on cortisol secretion in normal men.

In order to ascertain the subtype(s) of opioid receptors involved in the control of pituitary function the effects of four different opiate drugs (morphine, pentazocine, nalorphine and buprenorphine) were studied in four groups of six normal male volunteers. Each of the drugs tested induced, with varying degrees, both a significant increase in PRL and a significant decrease in LH and cortisol. On the contrary TSH secretion was stimulated by buprenorphine and morphine only and GH by nalorphine only. FSH did not change significantly after administration of any drug. Taking into account the different affinities of the drugs used by us for the different opioid receptors, our data do not allow to demonstrate a well-defined correlation between subtypes of opioid receptors and the control of pituitary hormone secretion. The possible explanations of this fact are discussed.

Adult↗

Nomenclature of secreted platelet proteins--report of the Working Party on Secreted Platelet Proteins of the Subcommittee on Platelets.

Standard nomenclature for a number of secreted platelet proteins was agreed upon by The Working Party on Secreted Platelet Proteins of the Subcommittee on Platelets. Platelet factor 4 will continue to be used for the molecule with high heparin affinity, subunit molecular weight of 7780, and the described amino acid sequence. beta-Thromboglobulin will be used to designate beta-Thromboglobulin (81 amino acids/subunit, beta-mobility on cellulose-acetate electrophoresis, pI 7), low-affinity platelet factor 4 (85 amino acids/subunit, gamma-mobility on cellulose-acetate electrophoresis, pI 8), and platelet basic protein (94 amino acids/subunit, pI 10) when these are measured immunologically in plasma, but that thromboglobulin with a superscript designation of the pI should be used when assays are conducted on samples after isoelectric focusing, and a subscript amino-terminal amino acid can be added when a purified protein is described. Thrombospondin will continue to be the designation for the high molecular weight trimer that has previously been called thrombospondin or glycoprotein G. Platelet derived growth factor will be used for the group of closely related proteins of molecular weight about 30,000 and isoelectric point about 10.

Animals↗

[Peptone-stimulated gastric secretion and antacids. Effect of antacids with various content of calcium, magnesium and aluminiumions on the peptone-induced secretion of gastric juice, double-blind study].

A double-blind-trial was performed to prove the effect of antacids containing Mg (OH)2, Al (OH)3 and CaCO3 on peptone-stimulated gastric secretion (intragastric titration). A high efficacy of antacids given after meals was demonstrated. After application of antacids no significant rise in serum gastrin levels during intragastric titration was found. Serum calcium and magnesium levels remained unchanged. Peptone-stimulated gastric secretion was not influenced by application of different antacids within a period of 2 hours.

Aluminum↗

Proliferative responses and IL-2 production by mononuclear cells from bovine mammary secretions, and the effect of mammary secretions on peripheral blood lymphocytes.

Mammary gland mononuclear cells (MGM) were compared with peripheral blood mononuclear cells (PBM) for their ability to proliferate in response to phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM), and to produce interleukin-2 (IL-2) when cultured with Con A. MGM proliferative responses to all three mitogens were at a level only just above background. Following removal of adherent cells by passage of the MGM population over Sephadex G10, their ability to proliferate increased but these responses were still significantly lower (P less than 0.001) than those of PBM. Mammary secretions from non-lactating cows and colostrum, but not milk, were found to suppress the proliferative responses to PHA and Con A of PBM following a 24-hr preincubation period. There was no difference in IL-2 production in response to Con A by Sephadex G10-treated MGM and PBM, and dry-cow secretions had no effect on IL-2 production.

Animals↗

Distribution of molecule numbers per secretion granule. A study of crystals in glucagon secreting cells.

The occurrence of a crystalline component in secretion granules of teleost A-cells (islets of Langerhans) has been used to derive, in Xi-phophorus helleri, the size distribution of secretion granules in terms of (glucagon) molecule numbers. The distribution is asymmetric with the arithmetical mean = 7.1 x 10(5), the median Q0.5 = 4.7 x 10(5), and the range from 8.5 x 10(4) to 4.5 x 10(6) molecules, as determined in a sample of 203 crystals from 9 specimens. This result is based on the following assumptions: The crystals are rhombic dodecahedra with a greater than 4.2 nm and space group P213, thus much resembling cubic porcine glucagon; they are teleost glucagon and contain the whole glucagon content of the granule. If the latter assumptions are rejected, the above molecule numbers become minimum numbers of protein molecules. A change to other space groups also compatible with the diffraction patterns observed would only double the above values. The values are compared with corresponding ones from other species and also from other types of endocrine cells and errors are discussed.

Animals↗

[Saliva secretion and concentration and secretion of salivary amylase in low-birth weight infants].

Saliva samples were collected in the first day of life from 22 newborn infants, weighing between 1,22-2,26 kg and 27 newborn infants, weighing between 2,60-3,80 (controls). After 30 days new samples were obtained from 11 children from the first group and 16 children from the control group. Related to capacity of saliva secretion from the control group, no significant difference was observed between both groups. Contrary what is observed for other enzymes of the digestive tract, secretion and concentration of salivary amylase is not affected in low birth weight infants.

Amylases↗

Phorbol ester-induced protein secretion in rat parotid gland. Relationship to the role of inositol lipid breakdown and protein kinase C activation in stimulus-secretion coupling.

When added to rat parotid gland slices incubated in vitro, 4 alpha-phorbol-dibutyrate (PDBu) induced a dose-dependent increase in protein secretion, but did not affect membrane permeability to K+ (as determined by 86Rb efflux). The response to PDBu was unaffected by the removal of extracellular Ca2+ and was not markedly potentiated by incubation with the phosphodiesterase inhibitor, methylisobutylxanthine. PDBu did not activate phospholipase C breakdown of inositol lipids as shown by a failure to increase formation of soluble inositol phosphates. When applied in combination with the Ca2+ ionophore, ionomycin, a secretory rate was obtained that was greater than the predicted sum of rates obtained when the two drugs were given alone. These results, when taken with the reported results of others, are consistent with an action of PDBu in activating protein kinase C and suggest that this enzyme plays an important role in the pathway linking receptor activation to protein secretion, but not K+ flux, in the parotid gland.

Animals↗

Hyperthyroidism due to a thyrotropin-secreting pituitary adenoma. Studies of thyrotropin and subunit secretion.

A 58-year-old man had symptoms of hyperthyroidism and congestive heart failure. While hyperthyroid, his serum thyrotropin (TSH) level was inappropriately elevated at 6.1 microunits/mL. The molar ratio of alpha subunit to TSH was 2.5, suggesting the presence of a TSH-secreting pituitary tumor. Further evaluation disclosed an enlarged sella turcica with posterior erosion, and an intrasellar mass was visualized on computed tomographic scan. Neither serum TSH nor alpha subunit levels became elevated after administration of thyrotropin-releasing hormone, nor were they suppressed by a dopamine infusion. Serum TSH but not alpha subunit levels rose during antithyroid drug therapy. Estrogens produced a partial reduction in serum alpha subunit concentration (presumably reflecting the nontumorous gonadotroph contribution to circulating alpha subunit). Dexamethasone completely suppressed serum TSH level but had no effect on the alpha subunit level, suggesting a differential feedback of glucocorticoids on TSH and alpha secretion. The patient was treated with pituitary irradiation rather than surgery because of his underlying heart disease.

Adenoma↗

[Pancreatic secretion in rats. A comparative study of basal and stimulated secretions in acute and chronic fistula conditions (author's transl)].

Two types of pancreatic fistulas were directly compared in Wistar rats, to define more accurately the differences between collecting pancreatic juice under anesthesia (acute fistula) and in awake restrained animals (chronic fistula). Basal outputs of water, bicarbonate and total protein were about then times larger in chronic than in acute animals; they could be larger than the maximal secretory rate in anaesthetized rats. As a corollary, the chronic preparation was less sensitive to ecbolic and hydrelatic stimulations, with respect to basal levels. It is concluded that chronic fistula rats display a highly stimulated state of pancreatic secretion, probably due to the potentiation of several neurohumoral factors. Whatever this stimulation originates from, it renders the model less suitable for studies on ancreatic stimulating agents. On the contrary, anaesthetized rats displayed a low secretion more responsive to stimulating agents.

Acetylcholine↗

[Unusual association of somatostatin-secreting thyroid cancer and a calcitonin-secreting duodenal endocrine tumor. Is it an entity?].

We report a patient with a vesicular thyroid carcinoma secreting somatostatin and associated to an endocrine duodenal calcitonin secreting tumour. Increase of plasm somatostatin level induced an endocrine syndrome which completely resolved after thyroidectomy. By contrast, the digestive tumour remained asymptomatic. Six months after surgery, the course was marked by a relapse of the thyroid tumour along with pulmonary metastasis. At that time, pathological analysis showed only indifferentiated tumoural tissue.

Aged↗

Expression of an uncleavable N-terminal RasGAP fragment in insulin-secreting cells increases their resistance toward apoptotic stimuli without affecting their glucose-induced insulin secretion.

Apoptosis of pancreatic beta cells is implicated in the onset of type 1 and type 2 diabetes. Consequently, strategies aimed at increasing the resistance of beta cells toward apoptosis could be beneficial in the treatment of diabetes. RasGAP, a regulator of Ras and Rho GTPases, is an atypical caspase substrate, since it inhibits, rather than favors, apoptosis when it is partially cleaved by caspase-3 at position 455. The antiapoptotic signal generated by the partial processing of RasGAP is mediated by the N-terminal fragment (fragment N) in a Ras-phosphatidylinositol 3-kinase-Akt-dependent, but NF-kappaB-independent, manner. Further cleavage of fragment N at position 157 abrogates its antiapoptotic properties. Here we demonstrate that an uncleavable form of fragment N activates Akt, represses NF-kappaB activity, and protects the conditionally immortalized pancreatic insulinoma betaTC-tet cell line against various insults, including exposure to genotoxins, trophic support withdrawal, and incubation with inflammatory cytokines. Fragment N also induced Akt activity and protection against cytokine-induced apoptosis in primary pancreatic islet cells. Fragment N did not alter insulin cell content and insulin secretion in response to glucose. These data indicate that fragment N protects beta cells without affecting their function. The pathways regulated by fragment N are therefore promising targets for antidiabetogenic therapy.

Animals↗

Stimulus-secretion coupling and insulin secretion in aging: evaluation of glucose oxidation and ATP-sensitive potassium channel responsiveness.

The purpose of this study was to evaluate possible age-related alterations in the glucose-stimulus/insulin-secretion coupling mechanism of islets of Langerhans. To this end, the interaction among insulin secretion, glucose oxidation, and ATP-sensitive potassium (K ATP) channel responsiveness was determined in islets of Langerhans isolated from 6-, 12-, and 26-month-old male Fischer 344 (F344) rats. Groups of 20 islets were incubated for 40 min at 37 degrees C in a buffer containing: (1) either 1.7 or 11.1 mM glucose; (2) 1.2 microM glyburide and either 1.7 or 11.1 mM glucose; (3) 5 microM epinephrine and 11.1 mM glucose; or (4) 1.2 microM glyburide, 5 microM epinephrine, and either 1.7 or 11.1 mM glucose. Insulin release of islets incubated in the presence of glyburide and 1.7 or 11.1 mM glucose was greater than that of islets incubated in glucose alone, while glucose oxidation did not increase. Epinephrine inhibited insulin release and glucose oxidation at 11.1 mM glucose and abolished glyburide-enhanced insulin release at 11.1 mM glucose. No effect of age was observed in any of the treatment categories. These results indicate that if age-related alterations are occurring in glucose-stimulus/insulin-secretion coupling, then such alterations are not associated with changes in K ATP channel-mediated responsiveness.

Adenosine Triphosphate↗

The stimulus-secretion coupling of amino acid-induced insulin release. XII. Contrasting effects of L-leucine and a nonmetabolized analog upon islet metabolism and insulin secretion.

L-Leucine and its nonmetabolized analog, 2-aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH), do not act identically in pancreatic islets. For instance, BCH stimulates more markedly than leucine the output of 14 CO2 from islets prelabelled with L-[U-14C] glutamine. Although leucine and BCH stimulate insulin release to the same extent in the presence of glutamine, the rate of secretion is higher in leucine-stimulated than in BCH-stimulated islets when 2-ketoisocaproate is present in the incubation medium alone or together with glutamine. Such a difference in secretory rate coincides with contrasting effects of leucine and BCH, respectively, on both NH4+ production and glutamine oxidation by the islets exposed to 2-keto-isocaproate. These differences are best explained by the inability of BCH, as distinct from leucine, to act as a transamination partner of 2-ketoglutarate, and emphasize the view that the secretory response to nutrients tightly depends on the regulation of catabolic events in the islet cells.

Amino Acids↗

Does nitric oxide play a role in stimulus-secretion and/or synthesis-secretion coupling of insulin?

By using the perfused rat pancreas model and the nitric oxide synthase inhibitor, nitro-arginine methyl ester (NAME), we examined the hypothesis that first-phase potentiation or second-phase inhibition of insulin release due to the amino acid arginine (or both) are the result of its conversion to nitric oxide (NO). In the presence of 16.7 mM glucose, 20 mM arginine caused a first-phase potentiation of insulin release when compared with glucose controls, while inhibiting the second-phase insulin release. When 20 mM NAME was added in addition to 20 mM arginine and 16.7 mM glucose, the total insulin released during the first secretory phase was not significantly different from that of the glucose plus arginine group, suggesting that inhibition of NO production does not affect arginine-potentiated first-phase insulin release. Similarly, the presence of NAME failed to reverse the arginine inhibition of second-phase insulin release. The presence of NAME resulted in a more pronounced inhibition of insulin secretion. Correspondingly, compared with the glucose-only controls, the presence of 20 mM NAME plus 16.7 mM glucose resulted in a significant decrease in insulin release during the second phase, whereas the presence of NAME did not affect first-phase glucose-stimulated insulin release. Thus we conclude that the conversion of arginine to nitric oxide does not play a significant role in glucose-stimulated first-phase potentiation or second-phase inhibition of insulin release due to arginine.

Analysis of Variance↗

Increased secretion of insulin but unchanged secretion of growth hormone in hyperglycaemic type II diabetics treated with acetyl-salicylic acid.

The effect of acetyl-salicylic acid (ASA, 3 g/d for three days) on basal and arginine-stimulated concentrations of insulin and growth hormone was studied in seven type II diabetics. From 120 min before until 120 min after the infusion of arginine-hydrochloride (30 g/30 min) blood glucose concentrations were clamped at hyperglycaemic levels both during treatment with ASA (blood glucose: 12.7 +/- 1.2 mmol/l) and during a control experiment without ASA (blood glucose: 12.9 +/- 1.3 mmol/l). Concentrations of serum insulin in the hyperglycaemic state prior to arginine infusion were increased during treatment with ASA, whereas increments of serum insulin induced by i.v. arginine were unaffected. No difference was seen in either basal or stimulated concentrations of growth hormone. Thus, ASA enhances glucose-induced secretion of insulin in type II diabetics but fails to potentiate the glucose-dependent suppression of arginine-stimulated growth hormone release. In contrast to the pancreatic beta-cell the glucose-sensitive regulatory mechanism of growth hormone release appears to be unaffected by the inhibition of endogenous prostaglandin synthesis.

Aged↗

Stimulus-secretion coupling of arginine-induced insulin release: comparison with lysine-induced insulin secretion.

L-Lysine, like-L-arginine, L-ornithine, or L-homoarginine, accumulated in rat pancreatic islets and stimulated 86Rb efflux, 45Ca uptake and efflux, and insulin release in islets exposed to D-glucose (7.0 mM). The effect of L-lysine differed from that of the other cationic amino acids by such features as the absence of a threshold concentration for stimulation of insulin release, a much lesser sensitivity of the secretory response to intracellular acidification, and the stimulation of 86Rb net uptake over 60 min of incubation. This coincided with the fact that even in the absence of another exogenous nutrient, L-lysine was well oxidized, augmented NH4+ production, increased both the ATP content and ATP/ADP ratio, caused a time-related decrease in 86Rb fractional outflow, and provoked either a transient (10 mM L-lysine) or sustained (20 mM L-lysine) stimulation of insulin secretion. It is proposed, therefore, that the functional response of the pancreatic B-cell to L-lysine involves not only a biophysical mechanism similar to that responsible for the insulinotropic action of L-homoarginine, but also a significant, albeit modest, metabolic component, which reflects the capacity of L-lysine to act as a fuel in islet cells.

Animals↗