Inhibition of pancreatic hormone secretion by somatostatin-28 and somatostatin-14 in man

1983 ◽  
Vol 104 (1) ◽  
pp. 91-95 ◽  
Author(s):  
L.J. Klaff ◽  
J. L. Barron ◽  
N. S. Levitt ◽  
N. Ling ◽  
R. P. Millar
Keyword(s):  
Hormone Secretion ◽  
Laboratory Animals ◽  
Normal Male ◽  
Carbohydrate Homeostasis ◽  
Pancreatic Hormone ◽  
Male Subjects ◽  
Somatostatin 14

Abstract. The effects of a 210 min infusion of 1.8 nmol/kg somatostatin-14 (SS-14), somatostatin-28 (SS-28), and vehicle (Haemaccel) alone, on arginine- and insulin-stimulated release of pancreatic hormones were tested in 5 normal male subjects. Arginine administered at 30–60 min induced an increase in plasma glucose concentrations which was enhanced by SS-14 and further increased by SS-28. SS-28 was more effective than SS-14 in suppressing the arginine-induced secretion of insulin. Arginine-stimulated and insulin-stimulated (at 120 min) glucagon release was equally suppressed by SS-14 and SS-28, as was insulin-stimulated pancreatic polypeptide secretion. At the end of the SS-14 infusion the mean plasma somatostatin level was approximately 28% of that which occurred during the SS-28 infusion. The results are discussed in relation to similar studies in vitro and in vivo in laboratory animals and to a possible role of the two forms of SS in carbohydrate homeostasis.

In-vitro control of growth hormone secretion by synthetic releasing factors in young and adult ducks (Anas platyrhynchos)

1988 ◽  
Vol 119 (3) ◽  
pp. 421-429 ◽  
Author(s):  
C. Foltzer-Jourdainne ◽  
S. Harvey ◽  
P. Mialhe
Keyword(s):  
Low Dose ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Age Related ◽  
Basal Release ◽  
Pituitary Glands ◽  
Releasing Factors ◽  
Somatostatin 14

ABSTRACT Release of GH from perifused duckling hemipituitaries was stimulated, in a biphasic manner, by synthetic TRH and human pancreatic GH-releasing factor (GRF). At all effective concentrations, the level of GH release was increased within 5 min of TRH or GRF perifusion and was maximal after 10 min of TRH perifusion and after 20 min of GRF perifusion. Although TRH was perifused for 20 min the level of GH release declined during the last 10 min. The most effective dose of TRH (1·0 μg/ml; 2·7 μmol/l) and GRF (0·5 μg/ml; 110 nmol/l) provoked similar (250– 300%) increases in the level of GH release. However, since the effect of TRH was only of short duration, the total release of GH induced by GRF was higher than that elicited by TRH, especially with the low dose. The increase in release of GH induced by TRH or GRF was blunted when pituitaries from adult ducks were used. As in young ducks, the GH response to GRF was higher, whereas the response to TRH was very low. The GH response of perifused adult pituitaries to GRF was, however, potentiated when TRH was perifused simultaneously. The basal release of GH from both young and adult pituitary glands was unaffected by perifusion with somatostatin-14 (SRIF-14) at doses of 1 and 2 μg/ml. The perifusion of hemipituitary glands with similar doses of SRIF-14 was also unable to suppress the stimulation of GH release induced by prior perifusion with GRF, although when SRIF-14 and TRH were simultaneously perifused TRH-induced GH release was markedly suppressed. These results demonstrate direct effects and interactions of TRH, GRF and SRIF on the release of GH from duck pituitary glands. GRF is the most potent releasing factor for GH in both young and adult ducks although in adult ducks it is less effective. These results also provide evidence that the age-related decline in the in-vivo GH response to TRH is due to a desensitization of pituitary somatotrophs. J. Endocr. (1988) 119, 421–429

Adaptive changes in insulin and glucagon secretion during cold acclimation in the rat

1986 ◽  
Vol 250 (6) ◽  
pp. E669-E676 ◽  
Author(s):  
C. I. Edwards ◽  
R. J. Howland
Keyword(s):  
Cold Acclimation ◽  
Cold Exposure ◽  
Hormone Secretion ◽  
Glucagon Secretion ◽  
Molar Ratio ◽  
Adaptive Process ◽  
Insulin And Glucagon Secretion ◽  
Pancreatic Hormone

Arginine-stimulated insulin and glucagon outputs from isolated perfused pancreata of warm-acclimated and 2-, 4-, and 6-wk cold-acclimated rats (4 degrees C) were determined to assess whether observed changes in these parameters were a result of cold exposure per se or a part of the adaptive process of cold acclimation. Progressive and sequential changes were seen in both insulin and glucagon outputs. At 2 wk cold acclimation, glucagon rose and insulin output tended to fall, at 4 wk, glucagon output remained elevated and insulin output was further reduced, and at 6 wk, glucagon output had returned to control levels, whereas insulin output was substantially further reduced. These changes resulted in reduction of the insulin-to-glucagon molar ratio of the total arginine-induced output from 7.27 +/- 1.76 (SE) in the warm acclimate to 2.31 +/- 0.79 (SE) at 2 wk, 1.42 +/- 0.29 (SE) at 4 wk, and 1.26 +/- 0.21 (SE) at 6 wk cold acclimation. The data do not provide in vitro support for the hypothesis that changes in pancreatic hormone secretion in vivo are a consequence of cold exposure and not cold acclimation.

scholarly journals SUN-266 Protein Induced Pancreatic Hormone Secretion Is Modulated by Vagal CaSR

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Mariana Norton ◽  
Simon C Cork ◽  
Aldara Martin Alonso ◽  
Anna G Roberts ◽  
Yateen S Patel ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hormone Secretion ◽  
Sensory Information ◽  
Glucagon Secretion ◽  
Vagal Afferents ◽  
Acid Uptake

Abstract The existence of a vago-vagal entero-pancreatic pathway, where sensory information from the gut can signal via vagal afferents to the brain to mediate changes in pancreatic function, has been recognised for over a century, and investigated extensively with regards to pancreatic exocrine secretions. However, the role of such pathways in pancreatic endocrine secretions has received less attention. The secretion of insulin and glucagon in response to protein and amino acids is conserved across species. This effect is thought to promote amino acid uptake into tissues without concomitant hypoglycaemia. We found that the essential amino acid L-Phenylalanine potently stimulates glucagon secretion, even when administered directly into the gut at small doses unlikely to significantly raise systematic levels. Administration of L-Phenylalanine also increased neuronal activation in the rat and mouse dorsal vagal complex, the central nervous system region directly innervated by vagal afferents. L-Phenylalanine modulates the activity of the calcium sensing receptor (CaSR), a nutrient sensor more commonly known for its role in calcium homeostasis, but which is thought to also act as a sensor of aromatic amino acids. Interestingly, the CaSR is one of the few nutrient sensors expressed in vagal afferents and in vitro calcium imaging revealed CaSR synthetic agonists activate subpopulations of vagal afferents. The role of CaSR in vivo was investigated further by selectively knocking down the CaSR in vagal afferents. Briefly, CaSR floxed mice were bilaterally injected directly into the nodose ganglion, where the cell bodies of vagal afferents are located, with a cre expressing adeno-associated virus. CaSR knockdown did not interfere with normal food intake, nor the vagal-dependent anorectic effects of cholecystokinin, or of L-Phenylalanine. However, it did blunt protein-induced glucagon secretion, suggesting involvement of the CaSR in the vagus nerve in protein sensing and glucose homeostasis. Future studies are required to determine the importance of vagal CaSR in protein induced pancreatic endocrine secretions, and the possibility of exploiting this circuit to develop new anti-diabetic therapies.

scholarly journals Analytical Review: The Kinetics of Granulopoiesis in Normal Man

Blood ◽  
1964 ◽  
Vol 24 (6) ◽  
pp. 780-803 ◽  
Author(s):  
G. E. CARTWRIGHT ◽  
J. W. ATHENS ◽  
M. M. WINTROBE
Keyword(s):  
Body Weight ◽  
Generation Time ◽  
Turnover Time ◽  
Normal Male ◽  
The Mean ◽  
Time Required ◽  
Kinetics Of ◽  
Male Subjects

Abstract Present knowledge concerning the kinetics of granulopoiesis has been reviewed and quantitative data concerning granulokinetics in normal human subjects are presented. A. When granulocytes are labeled in vitro and returned to the circulation of the donor, the distribution of the cells in the circulation and the rate of disappearance of the cells from the circulation can be measured. 1. The total blood granulocyte pool (TBGP) consists of two compartments which are in equilibrium with each other. These pools have been designated the circulating granulocyte pool (CGP) and the marginal granulocyte pool (MGP). The size of the pools has been measured in 109 normal male subjects. The mean values, expressed as numbers of cells x 107 per Kg. of body weight were as follows: TBGP, 70; CGP, 31; and MGP, 39. The mean ratio of the CGP to the TBGP was 0.44. 2. The labeled granulocytes leave the TBGP in an exponential fashion with a mean half-time disappearance (T½) of 6.7 hours as determined in 56 normal male subjects. No evidence has been obtained for a return of granulocytes to the blood. 3. The mean value for the granulocyte turnover rate (GTR) in 56 normal male subjects was 163 x 107 granulocytes per Kg. of body weight per day. Thus, the TBGP turns over 2.3 times per day and the turnover time for the TBGP is 10.4 hours. B. When granulocytes are labeled in vivo by the intravenous administration of DFP32, the rate of disappearance of granulocytes from the circulation and the time required for myelocytes to divide, mature and appear in the blood can be measured. In addition, the generation time of myelocytes can be approximated. From the time parameters and the GTR, the bone marrow pool sizes and turnover times can be calculated. These determinations and calculations have been made for a group of 21 normal male subjects. 1. The mean half-time disappearance (T½) of in vivo labeled granulocytes from the circulation was 7.2 hours. This value agrees well with the value of 6.7 hours obtained after the in vitro labeling of granulocytes. 2. The mean time required for myelocytes to divide, mature and appear in the blood was 11.4 days. 3. The mean generation time of myelocytes was estimated to be not more than 2.9 days. 4. The total granulocyte pool in the bone marrow (neutrophilic myelocytes, neutrophilic metamyelocytes and PMN neutrophils) was calculated to be 186 x 108 cells per Kg. of body weight with a mean turnover time of 11.4 days. The myelocyte pool was estimated to be 41 x 108 cells per Kg. with a turnover time of 2.5 days; the metamyelocyte pool consisted of about 76 x 108 cells per Kg. with a turnover time of 4.7 days; the average size of the mature marrow PMN neutrophil pool was 69 x 108 cells per Kg. of body weight with a turnover time of 4.2 days. C. A kinetic model for granulopoiesis, based on the studies with the DFP32 label, is presented. In this model, myelocytes are depicted as approaching a self-perpetuating population of cells. Some cells enter this population from populations which are less mature but this latter source of cells is small under conditions of normal steady state kinetics. One of the daughter cells of a myelocyte division remains in the myelocyte population to divide again. The other daughter cell enters the metamyelocyte population. The metamyelocyte and PMN neutrophil population is incapable of division and cells move through this population in sequential fashion in the process of maturation. The cells then enter the blood where they equilibrate rapidly between the two blood compartments. The cells are removed from the total granulocyte pool in a random fashion. There is no appreciable pool of granulocytes in the extramedullary tissues of normal subjects and granulocytes do not return from the tissues to the blood. The entire movement of granulocytes from marrow to tissues is uni-directional.

scholarly journals The role of somatostatin and dopamine D2 receptors in endocrine tumors

2011 ◽  
Vol 18 (6) ◽  
pp. R233-R251 ◽  
Author(s):  
Federico Gatto ◽  
Leo J Hofland
Keyword(s):  
Pituitary Adenomas ◽  
Hormone Secretion ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Negative Control ◽  
Endocrine Tumors ◽  
Wide Group

Somatostatin (SS) and dopamine (DA) receptors have been highlighted as two critical regulators in the negative control of hormonal secretion in a wide group of human endocrine tumors. Both families of receptors belong to the superfamily of G protein-coupled receptors and share a number of structural and functional characteristics. Because of the generally reported high expression of somatostatin receptors (SSTRs) in neuroendocrine tumors (NET), somatostatin analogs (SSA) have a pronounced role in the medical therapy for this class of tumors, especially pituitary adenomas and well-differentiated gastroenteropancreatic NET (GEP NET). Moreover, NET express not only SSTR but also frequently dopamine receptors (DRs), and DA agonists targeting the D2receptor (D2) have been demonstrated to be effective in controlling hormone secretion and cell proliferation inin vivoandin vitrostudies. The treatment with SSAs combined with DA agonists has already been demonstrated efficacious in a subgroup of patients with GH-secreting pituitary adenomas and few reported cases of carcinoids. The recent availability of new selective and universal SSA and DA agonists, as well as the chimeric SS/DA compounds, may shed new light on the potential role of SSTR and D2as combined targets for biotherapy in NET. This review provides an overview of the latest studies evaluating the expression of SSTR and DR in NET, focusing on their co-expression and the possible clinical implications of such co-expression. Moreover, the most recent insights in SSTR and D2pathophysiology and the future perspectives for treatment with SSA, DA agonists, and SS/DA chimeric compounds are discussed.

Role of stress proteins and hormones in bioregulation of ontogeny

2015 ◽  
Vol 61 (4) ◽  
pp. 49-53
Author(s):  
V I Goudochnikov
Keyword(s):  
World Literature ◽  
Stress Proteins ◽  
Primary Cultures ◽  
Experimental Studies ◽  
Theoretical Research ◽  
Laboratory Animals ◽  
Present Moment

In this short review article we tried to overview diffusely spread data on the role of stress proteins and hormones in ontogeny. The work presented here is a product of our long-term studies beginning from the middle of eighties of the last century and performed both in Russia and Brazil. It involves the results obtained with the use of experimental models on laboratory animals in vivo and in vitro, as well as later theoretical research in world literature databases. In experimental studies we used laboratory rats of different age groups and primary cultures of pituitary and liver cells for evaluating respectively body and organ growth and production of immunoreactive growth hormone (GH) and serum albumin (SA), as well as biosynthesis of DNA, total RNA and protein. The results obtained, showing important role of glucocorticoids (GC) in regulation of perinatal pituitary and liver functions and postnatal growth, were reinterpreted by us recently in the frame of DOHaD concept and as related to perinatal imprinting/programming phenomena. It is concluded that the present moment is quite appropriate for the widening of our studies both to the side of early embryonal development and in direction to aging, thus completing the whole cycle of life history / course research, as referred to stress proteins and hormones.

scholarly journals Hormones in experimental autoimmune encephalomyelitis (EAE) animal models

2021 ◽  
Vol 12 (1) ◽  
pp. 164-189
Author(s):  
Majid Ghareghani ◽  
Amir Ghanbari ◽  
Ali Eid ◽  
Abdullah Shaito ◽  
Wael Mohamed ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Endocrine System ◽  
Laboratory Animals ◽  
Autoimmune Encephalomyelitis ◽  
Eae Model ◽  
Experimental Autoimmune

Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) in which activated immune cells attack the CNS and cause inflammation and demyelination. While the etiology of MS is still largely unknown, the interaction between hormones and the immune system plays a role in disease progression, but the mechanisms by which this occurs are incompletely understood. Several in vitro and in vivo experimental, but also clinical studies, have addressed the possible role of the endocrine system in susceptibility and severity of autoimmune diseases. Although there are several demyelinating models, experimental autoimmune encephalomyelitis (EAE) is the oldest and most commonly used model for MS in laboratory animals which enables researchers to translate their findings from EAE into human. Evidences imply that there is great heterogeneity in the susceptibility to the induction, the method of induction, and the response to various immunological or pharmacological interventions, which led to conflicting results on the role of specific hormones in the EAE model. In this review, we address the role of endocrine system in EAE model to provide a comprehensive view and a better understanding of the interactions between the endocrine and the immune systems in various models of EAE, to open up a ground for further detailed studies in this field by considering and comparing the results and models used in previous studies.

scholarly journals Effects of KiSS-1 Peptide, the Natural Ligand of GPR54, on Follicle-Stimulating Hormone Secretion in the Rat

Endocrinology ◽  
2005 ◽  
Vol 146 (4) ◽  
pp. 1689-1697 ◽  
Author(s):  
V. M. Navarro ◽  
J. M. Castellano ◽  
R. Fernández-Fernández ◽  
S. Tovar ◽  
J. Roa ◽  
...  
Keyword(s):  
Excitatory Amino Acid ◽  
Hormone Secretion ◽  
Metastasis Suppressor ◽  
Experimental Conditions ◽  
Adult Rats ◽  
Gonadotropin Secretion ◽  
Neuroendocrine Control

Abstract KiSS-1 was originally identified as a metastasis suppressor gene encoding an array of structurally related peptides, namely kisspeptins, which acting through the G protein-coupled receptor GPR54 are able to inhibit tumor progression. Unexpectedly, a reproductive facet of this newly discovered system has recently arisen, and characterization of the role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion has been initiated. However, such studies have been so far mostly restricted to LH, and very little is known about the actual contribution of this system in the regulation of FSH release. To address this issue, the effects of KiSS-1 peptide on FSH secretion were monitored in vivo and in vitro under different experimental conditions. Intracerebroventricular administration of KiSS-1 peptide significantly stimulated FSH secretion in prepubertal and adult rats. Yet, dose-response analyses in vivo demonstrated an ED50 value for the FSH-releasing effects of KiSS-1 of 400 pmol, i.e. approximately 100-fold higher than that of LH. In addition, systemic (ip and iv) injection of KiSS-1 significantly stimulated FSH secretion in vivo. However, KiSS-1 failed to elicit basal FSH release directly at the pituitary level, although it moderately enhanced GnRH-stimulated FSH secretion in vitro. Finally, mechanistic studies revealed that the ability of KiSS-1 to elicit FSH secretion was abolished by the blockade of endogenous GnRH actions, but it was persistently observed in different models of leptin insufficiency and after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e. relevant signals in the neuroendocrine control of gonadotropin secretion. In summary, our results extend previous recent observations on the role of KiSS-1 in the control of LH secretion and provide solid evidence for a stimulatory effect of KiSS-1 on FSH release, acting at central level. Overall, it is proposed that the KiSS-1/GPR54 system is a novel, pivotal downstream element in the neuroendocrine network governing gonadotropin secretion.

Tumor Necrosis Factor in the Pathogenesis of Human Diseases

1992 ◽  
Vol 5 (2) ◽  
pp. 131-134
Author(s):  
P. Ghezzi
Keyword(s):  
New York ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Biological Activities ◽  
Laboratory Animals ◽  
Hemorrhagic Necrosis ◽  
Necrosis Factor

This paper will deal with the role of tumor necrosis factor (TNF) in the pathogenesis of various diseases. However, it will be important to remember that originally TNF was characterized as an antitumor factor. In fact, it was known that endotoxin was able to induce hemorrhagic necrosis of some tumors in mice. In 1975 Carswell et al. demonstrated the presence of a tumor necrotizing activity (termed “tumor necrosis serum”) in the sera of mice primed with C. parvum or BCG, and subsequently injected with endotoxin (1). Later it was found that this factor was a macrophage product and was termed TNF. In vivo TNF induced hemorrhagic necrosis of Meth A sarcoma and in vitro demonstrated cytotoxic activity against various tumor cell lines (2). In 1984, TNF was purified and its cDNA was cloned, and the production of substantial amounts of recombinant TNF allowed the characterization of its various biological activities (3). In parallel to these studies on tumor necrosis, the group of Cerami, at the Rockefeller University in New York was studying the mechanisms of cachexia and wasting associated with infection. They found that infection or injection of endotoxin in laboratory animals resulted in a marked hypertrygliceridemia, which was associated with an inhibition of lipoprotein lipase. They hypothesized that a host-derived mediator was responsible for this and other metabolic derangements observed in infection. This factor, which was termed “cachectin”, was later found to be produced by macrophages, and once it was purified and sequenced it became clear that TNF and cachectin were identical (4).

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

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