Abstract. Duck isolated perfused pancreas was used to assess glucose, adrenergic mediated effects and pancreatic function interrelationships. A moderate physiological 50% increase in glucose level, corresponding closely to the difference observed between 24-h-fasted and fed animals, induced a significant decrease of pancreatic glucagon not due to a rise in somatostatin secretion. The great responsiveness of the A cell was still found after glucagon stimulation by catecholamines or β adrenergic agonism. Insulin was irresponsive to the glucose load we used, suggesting that glucose-induced glucagon suppression was also insulin independent. As far as the D cell was concerned, glucose had no effect on pancreatic somatostatin output; however, an interesting finding was that β adrenergic agonism has a permissive effect on D cell responsiveness to the nutriment.
R. Gross and P. Mialhe
Abstract. The isolated perfused duck pancreas was used to study the effect of free fatty acids (FFA) on pancreatic function in vitro and to determine whether the FFA-glucagon negative feedback mechanism resulted from a direct inhibitory effect of FFA on the pancreatic A cell. Oleate, 2 mmol/l, increased the output rates of pancreatic somatostatin, glucagon and insulin. As there is poor morphological evidence in the duck for somatostatin to act as a paracrine intra-islet modulator, we reproduced in the pancreatico-duodenal artery, the rise in somatostatin level obtained in the pancreatic effluent after oleate. In these conditions the rises in glucagon and insulin secretions after oleate treatment were, respectively, reversed and suppressed, thereby reproducing observations previously made in vivo. Consequently, we may assume that the negative FFA-glucagon feedback mechanism that operates in vivo for physiological FFA variations does not result from a direct effect of FFA on the A cell, but may rather be mediated by an increase in pancreatic somatostatin secretion.
F. Gross, P. Loustalot and R. Meier
In a previous experiment it was found that daily doses of 0.04 mg. of d-aldosterone administered to rats for 4 weeks did not produce any hypertension while daily doses of 1 mg. of cortexone-acetate (DOCA) which have a comparable sodium retaining activity produced a typical increase in blood pressure (Gross, Loustalot & Meier, 1955). On the other hand Gornall et al. (1957) reported that very small doses of aldosterone (0.5–1.0 μg. daily or every two days) produced hypertension in rats within six months of treatment independently of the salt intake (Gornall et al., 1957; Kumar et al., 1956; Kumar et al., 1957). These findings, however, have not been confirmed by Gaunt et al. (1957).
Since larger amounts of aldosterone have recently become available, it has been possible to undertake further overdosage experiments in order to evaluate the possible hypertensive activity of aldosterone and to compare it with that of cortexone.
P. R. Gross, K. W. Gross, A. I. Skoultchi and J. V. Ruderman
According to the masked maternal messenger RNA hypothesis, a large part if not all the protein synthesis of early development is directed by mRNA already present in the cytoplasm of unfertilized eggs. This mRNA is supposed to be synthesized during oogenesis and stored in some unavailable form until some later time in development, when it is selectively associated with the translational machinery. To the indirect evidence, which is nevertheless very strong, there can now be added a direct proof of the hypothesis for the case of histone mRNA. The five main histones of sea urchin embryos are synthesized on small polyribosomes, directed in part by newly-synthesized messages that sediment as a group at about 9S. Some histone synthesis survives total transcription block, however, suggesting that maternal histone mRNA exists. In competition-hybridization experiments, the egg RNA is shown to contain sequences characteristic of functional, embryonic histone mRNA. The competing RNA is localized in ribonucleoprotein particles of egg homogenates that sediment at 20–40S. These same particles contain RNA that stimulates a cell-free heterologous system to synthesize sea urchin histones. The application of these facts to some problems of translation control and of development generally is discussed.
G. Ribes, R. Gross, D. Chenon and M. M. Loubatières-Mariani
Abstract. The effect of insulin on basal pancreaticoduodenal output of SRIH was investigated in vivo and compared in normal and alloxan diabetic dogs. The experiments were performed on anesthetized dogs having a T-shaped catheter inserted into the pancreaticoduodenal vein just at the exit of the pancreas for blood sampling. In normal dogs, an insulin infusion (1 IU/kg for 20 min) or an iv insulin injection (0.2 IU/kg over 30 sec) produced, before any change in glycemia, an immediate reduction of the venous pancreaticoduodenal output of SRIH. Then pancreaticoduodenal output of SRIH rose close to starting values and decreased again when blood glucose level became very low. In alloxandiabetic dogs, insulin infusion (1 IU/kg for 20 min) also induced an immediate inhibitory effect on pancreaticoduodenal SRIH output; the effect was more transient and from 20 min, unlike in normal dogs, an increase in pancreaticoduodenal output of SRIH was observed. In conclusion, exogenous insulin induces an immediate reduction in pancreaticoduodenal SRIH secretion both in normal and diabetic dogs, independently of basal blood glucose level and before any change in glycemia. In contrast, the delayed effect is different: SRIH secretion is reduced in normal dogs, whereas it is enhanced in diabetic dogs.
R. Hepp, K. Garbade, P. Oster and F. Gross
In unilaterally nephrectomized rats, 9α-fluorocortisol (9α-FF), in doses of 0.3 and 1.0 mg given daily by intramuscular injection, induced an increase in blood pressure that was independent of additional sodium supply.
9α-FF reduced weight gain and, in the dose of 1.0 mg, increased fluid turnover when 0.9 % saline was given to drink. Haematocrit values were elevated, whether saline or water was given as drinking fluid.
The serum sodium concentration was increased when saline was offered, but normal with water as drinking fluid. The serum potassium concentration was diminished in all groups that received 9α-FF.
The renin content of the kidney was markedly depressed in all groups that had 9α-FF. The degree of suppression was similar in the groups that had saline and those that had water to drink. Under 9α-FF, plasma concentration of angiotensin II was virtually zero when saline was given to drink, but about ¼ to ½ normal when drinking fluid was water.
It is concluded that the type of hypertension developing under high doses of 9α-FF resembles glucocorticoid rather than mineralocorticoid hypertension.
A. Zerbib, G. Ribes, R. Gross, R. Puech and M. M. Loubatières-Mariani
Insulin and pancreatic somatostatin secretions were studied after stimulation with an arginine infusion (5 mmol/1) in isolated perfused pancreata of adult streptozotocin-diabetic rats. In the presence of 2.8 mmol/l glucose, arginine clearly stimulated insulin and somatostatin secretions in diabetic rats, whereas it was ineffective in normal rats. Thus, not only the B-cells, but also the D-cells of the pancreas from streptozotocindiabetic rats are hypersensitive to arginine. The infusion of insulin (4 U/l) did not modify this hypersensitivity of the D-cells to arginine in pancreata of streptozotocindiabetic rats.
O. Spira, I. Vlodavsky, R. Ulmansky, R. Atzmon, Z. Fuks, A. Gordon and J. Gross
Abstract. Hypothyroid rat pituitary cells were cultured on an extracellular matrix (ECM) produced by corneal endothelial cells. ECM markedly affected the following parameters.
Cell attachment, spreading and proliferation were improved, resulting in a more rapid formation of confluent cell monolayers.
In the presence of ECM the production of both thyrotrophin (TSH) and growth hormone (GH) was larger than in its absence. Immunofluorescence studies revealed that 20% of the cells in these monolayers were thyrotrophs; consequently, TSH content was higher while GH level was lower than in control cultures of euthyroid pituitaries. These data suggest that the in vivo physiological differences are maintained by the conditions of the culture.
ECM enabled the response of both the somatotrophs and the thyrotrophs to thyrotrophin releasing hormone (TRH) and the cells remained responsive for at least 10 days. Maximal stimulation (1.3- to 6-fold) was obtained with 14 nm of TRH. In the absence of ECM the cells failed to respond to TRH.
Cell morphology was examined by scanning electron microscopy (SEM). Cells grown on ECM were characteristically epithelial, whereas those cultured on plastic plates had a fibroblast-like appearance. Four types of cells were identified in the epithelial cell monolayers by the appearance of their surface. TRH induced a 2-fold increase in the number of cells covered with microvilli and a corresponding decrease in the number of smooth surfaced cells. This suggests that hormone secretion is associated with the formation of microvilli.
D. Deville de Perière, D. Hillaire-Buys, R. Gross, R. Puech and S. Arancibia
Abstract. To investigate whether systemic insulin levels can influence somatostatin-like immunoreactivity and insulin-like immunoreactivity concentrations in the rat submandibular salivary glands, we measured the concentrations of the two peptides in an experimental group rendered diabetic by streptozotocin administration. The diabetic group showed a low plasma level of insulin compared with the control group: 0.5 ± 0.1 vs 3.5 ± 0.8 μg/l, (P< 0.01). Concomitantly, they exhibited clear glucosuria and a blood glucose level which was four times higher than in normal animals: 35.5 ± 1.4 vs 8.8 ± 0.8 mmol/l, (P< 0.001). The two peptide concentrations in the submandibular glands of diabetic rats showed an increase compared with controls: 42.9 ± 4.7 protein vs 24.7 ± 3.1 pg/mg protein (P< 0.001) and 34.9 ± 4.9 protein vs 18.4 ± 4.0 pg/mg protein (P< for insulin-like immunoreactivity concentration and somatostatin-like immunoreactivity concentration, respectively. Chronic insulin treatment of diabetic rats reversed the increase in somatostatin, but had no effect on the increase in insulinlike immunoreactivity concentration. A negative correlation (r = 0.24, P< 0.05) was found between the plasma insulin level and the somatostatin concentration of the submandibular glands. Our results suggest that the submandibular glands of rats may participate in the peripheral regulation of glucose homeostasis.
F. Laurent, H. Karmann, R. Gross, M. T. Strosser and P. Mialhe
Abstract. Glucagon, somatostatin and insulin secretions were evaluated in a new type of perfusion preparation: the naturally A and D cell rich splenic bulb of duck pancreas. Stable basal levels were observed with 11 mm glucose, corresponding to normoglycaemia, and all secretions were stimulated by 1 mm 3-isobutyl-1-methyl xanthine and by 10 mm arginine, demonstrating the technique's validity. In the absence of aminoacids in the perfusion medium, A cell blindness to glucose was corrected by physiological levels of insulin (2 ng/ml); insulinodependency of A cells, and unresponsiveness of D cells to glucose, probably not ruled by insulin, were observed. However, in the presence of aminoacids, glucagon was inhibited and somatostatin secretion stimulated by glucose (33 mm), independently of insulin (2 ng/ml). Aminoacids greatly influenced pancreatic hormone release.