Effect of nicotine on insulin secretion in the isolated perfused rat pancreas]

Insulin secretion induced by glucose (1.5 g/l) is changed by nicotine infusion; the recorded changes depend on the nicotine concentration uses. 1) At a low concentration (0.05 mM) nicotine provokes an immediate, progressively increasing and lasting stimulation of insulin secretion. This stimulation is inhibited by hexamethonium (0.1 mM) and atropine (0.3 micrometer). 2) At a high concentration (1 mM) nicotine has a triphasic effect on insulin secretion : brief decrease, peak of stimulation and prolonged decrease. Hexamethonium decreases the stimulation and suppresses the prolonged inhibition.     

Anion secretion by the isolated rabbit pancreas

The isolated rabbit pancreas secretes a fluid containing chloride and bicarbonate in about equal concentrations. Replacement of bicarbonate by acetate, phosphate or isethionate, replacement of Na⁺ by Li⁺ and addition of ouabain to the bathing medium of the pancreas inhibit the secretion of fluid, chloride and bicarbonate in a similar fashion and by maximally 100%. Replacement of chloride by isethionate inhibits fluid secretion by maximally 50%, chloride secretion by 90% and bicarbonate secretion by 20%. It is concluded that fluid secretion is based on a Na⁺-gradient-dependent bicarbonate influx or proton efflux in the ductular cell, and that the secretion of chloride is secondary to that of bicarbonate.     

Pathways of secretion in the exocrine pancreas: the status of resting secretion

In the last decade the concept of two distinct pathways of secretion in the exocrine pancreas has slowly emerged. According to this concept, one pathway is involved in stimulated (regulated) conditions and another under resting (constitutive) conditions. This hypothesis was elaborated at first from the comparison of the specific radioactivities of secretory proteins released by the gland under resting and stimulated conditions. Analysis of the protein composition of the juice released under these two physiological conditions further supported that hypothesis. More recent studies compared the kinetic of accumulation of newly synthesized proteins in zymogen granule and their release in the gland lumen. The latter results are in agreement with a model in which secretory proteins are channelled in two separate pathways, one regulated, and one constitutive. Essentially, the constitutive pathway would correspond to a paragranular route in which the proteins would be immediately secreted instead of being stored in zymogen granules. In addition, some of the proteins released in the juice under "resting" conditions are associated to microvesicles. The term "microvesicular secretion" is used to designate that type of secretion.     

Nonparallel secretion of enzymes by the rabbit pancreas

Since nonparallel secretion of enzymes by the exocrine pancreas has been demonstrated with several experimental models, we were interested in verifying a recent claim that enzyme secretion remained strictly proportional (parallel) upon stimulation of the in vivo rabbit pancreas. Pancreatic juice was collected by extraduodenal cannulation of the pancreatic duct, in two different protocols. In the first protocol the administration of pentobarbital induces a mild anesthesia. Under this condition, amylase and chymotrypsin secretion remained parallel after cholecystokinin stimulation. In a second protocol, a deeper and constant anesthesia was attained with Fluothane resulting in a lower basal protein output than in the first protocol. Pancreatic secretion was collected under intravenous secretin perfusion (4.5 clinical units X kg-1 X h-1). After stabilization and basal collection periods, pancreatic secretion was stimulated with an i.v. bolus injection of either cholecystokinin (2 Ivy dog units/kg), caerulein (0.1 micrograms/kg), or carbachol (6 micrograms/kg). Upon stimulation of the pancreas, protein output increased an average of 30-fold and there was a concomitant 20-25% decrease in the ratio of the specific activities of amylase to chymotrypsin which resulted from a greater increase in the specific activity of chymotrypsin in pancreatic juice after stimulation of secretion. Thus, under appropriate conditions, nonparallel secretion of enzymes by the exocrine pancreas can be demonstrated in yet another experimental model. Furthermore, the proportion of amylase and chymotrypsin activities in pancreatic juice are once more shown to be dependent, up to a threshold, upon the rate of protein output by this exocrine gland.     

Regulation of hormone secretion in primary cell cultures of human somatotropinomas]

The effects of somatostatin and thyroliberin (thyrotropin-releasing hormone; TRH) on growth hormone (GH) and prolactin (PRL) secretion were studied in short-term (0.5-3h) or long-term (21-24h) incubations using monolayer cell cultures of somatotropin obtained from surgical material of patients with acromegaly. High sensitivity of both GH and PRL release to inhibitory action of somatostatin (10(-11) M) was established. We could not reveal the unambiguous influence of TRH on somatotropic function in the in vivo and in vitro conditions, as compared to the action of this tripeptide on PRL secretion. The results obtained permit us to propose that cell cultures of pituitary adenomata represent adequate and convenient models for studying the pathogenesis of tumor processes in the pituitary gland and for the development of new procedures of pharmacotherapy.     

Regulation of surfactant secretion

Lung surfactant is synthesized in the alveolar type II cell. Its lipids and hydrophobic proteins (SP-B and SP-C) are stored in lamellar bodies and secreted by regulated exocytosis. In contrast, the hydrophilic proteins (SP-A and SP-D) appear to be secreted independently of lamellar bodies. Regulation of surfactant secretion is mediated by at least three distinct signaling mechanisms: activation of adenylate cyclase with formation of cAMP and activation of cAMP-dependent protein kinase; activation of protein kinase C; and a Ca(2+)-regulated mechanism that likely results in the activation of Ca(2+)-calmodulin-dependent protein kinase. These signaling mechanisms are activated by a variety of agonists, some of which may have a physiological role. ATP is one such agent and it activates all three signaling mechanisms. There is increasing information on the identity of several of the signaling proteins involved in surfactant secretion although others remain to be established. In particular the identity of the phospholipase C, protein kinase C and phospholipase D isomers expressed in the type II cell and/or involved in surfactant secretion has been established. Distal steps in the secretory pathway beyond protein kinase activation as well as the physiological regulation of surfactant secretion, are major issues that need to be addressed.     

Regulation of gonadal androgen secretion

The various mechanisms regulating testicular and ovarian androgen secretion are reviewed. Testicular androgen secretion is controlled by luteinizing hormone (LH) and follicle stimulating hormone (FSH), which influence the Leydig cell response to the LH. The contribution of prolactin, growth hormone and thyroid hormones to the Leydig cell function is discussed. The ovarian androgen secretion is regulated in a very similar fashion as the Leydig cell of testis. Prolactin, however, has an inhibitory effect on androgen secretion in the ovary. The intratesticular action of androgens is linked to spermatogenesis. Sertoli cells, by producing the androgen-binding protein, contribute to the intratubular androgen concentration. Inhibin production of the Sertoli cell is stimulated by androgens. In the ovary, androgens produced by the theca interna are used as precursors for the aromatization of estradiol, which stimulates together with FSH the mitosis of granulosa cells. The feedback control of androgen secretion is complicated, as the direct feedback mechanisms are joined by indirect feedback regulations like the peptide inhibin, which can be stimulated by androgens. Intragonadal mechanisms regulating androgen production are the cybernins for testicles and ovaries. In the testicle, estrogens from the Sertoli cells regulate the Leydig cell testosterone biosynthesis. In the ovary, nonaromatizable androgens are potent inhibitors of the aromatization activity in the granulosa cell. A peptide with a FSH receptor binding inhibiting activity is found in male and female gonads. Finally, LH-RH-like peptides have been found in the testicle, which are capable of inhibiting steroidogenesis. These gonadocrinins are similarly produced in granulosa cells of the ovary.     

Ionic transport mechanisms underlying fluid secretion by the pancreas

The pancreas is a 'leaky' epithelium and secretes a juice in which sodium and potassium have concentrations similar to those of plasma. The characteristic features of the secretion are its isosmolality and its high bicarbonate concentration. It is the latter that has attracted considerable attention. Secretion in the isolated cat pancreas is directly proportional to the bicarbonate concentration in the nutrient fluid. The ability of the gland to secrete weak acids has led to the view that because of the very different chemical nature of the anions, it is most likely that it is a component common to all buffers, the proton, that is subject to active transport. This is supported by the decrease in pH and the increase in rho CO2 of the venous effluent when secretion occurs and the sensitivity of secretion to the pH of the nutritional extracellular fluid. It is proposed that the cellular mechanisms are as follows: CO2 diffuses into the cell and is hydrated to carbonic acid under the influence of carbonic anhydrase. The bicarbonate ion so formed diffused into the ductular lumen and the proton is transported backwards through the epithelium with a proton pump (Mg2+ -ATPase) provisionally located in the luminal membrane and a hydrogen-sodium exchange carrier located in the basolateral membrane. Energy for the latter process is derived from the sodium gradient between extracellular fluid and cell. This gradient is maintained by a (Na+ + K+)-ATPase also located in the basolateral membrane. Chloride appears to be transported partly through a chloride-bicarbonate exchange mechanism but largely passively together with a large sodium and potassium component through the paracellular pathway. Osmotic equilibrium is likely to occur in the small ductules.     

A model for fluid secretion in the exocrine pancreas

Fluid secretion by the isolated rabbit pancreas is strongly dependent on the presence of Na+ in the bathing medium. Substitution of Na+ by another cation such as Li+ or K+ causes an inhibition of fluid secretion rate and a change in the composition of the secreted fluid which is dependent on the nature of the substituent cation. Stimulation of the pancreas by CCK-8 or carbachol increases paracellular ion permeability and, in some cases, also fluid secretion rate. We present a simple, quantitative model for ion and water secretion which accounts for the effects observed upon Na+ substitution and stimulation. The main features are active, Na+-dependent transcellular HCO3- transport and passive, paracellular cation and anion permeation. The activity of the HCO3- pump is dependent on the energy status of the cell and on the Na+ concentration in the bathing medium, and is competitively inhibited by K+. The paracellular ion permeabilities can be modulated by stimulatory agonists. We examine the extent to which, according to the model, fluid secretion is controlled by the various system parameters such as ion permeabilities and ion pump activity, and by external parameters such as the ion concentrations in the bathing medium. In addition, calculation of the effects of changes in these parameters are carried out in order to gain more insight in the mechanisms of secretion.     

Correlation between lactate output and insulin secretion of the isolated perfused rat pancreas under the influence of high concentrations of phenformin]

On the isolated perfused rat pancreas phenformin at high concentrations (10 mg/1, 50 mg/1 and 100 mg/1) provokes an increase of the insulin and lactate output in the effluent liquid. In no case is glucagon secretion modified by this substance. There exists a statistically significant correlations between the increase in insulin output and the increase in lactate output induced by phenformin.