scholarly journals UTS2B Defines a Novel Enteroendocrine Cell Population and Regulates GLP-1 Secretion Through SSTR5 in Male Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (12) ◽  
pp. 2849-2860
Author(s):  
Cong Tang ◽  
Iwona Ksiazek ◽  
Noemie Siccardi ◽  
Berangere Gapp ◽  
Delphine Weber ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Peptide Hormone ◽  
Fine Tuning ◽  
Enteroendocrine Cell ◽  
Gut Hormone ◽  
Cellular Source ◽  
Glucagon Like Peptide 1

Abstract The gut-pancreas axis plays a key role in the regulation of glucose homeostasis and may be therapeutically exploited to treat not only type 2 diabetes but also hypoglycemia and hyperinsulinemia. We identify a novel enteroendocrine cell type expressing the peptide hormone urotensin 2B (UTS2B). UTS2B inhibits glucagon-like peptide-1 (GLP-1) secretion in mouse intestinal crypts and organoids, not by signaling through its cognate receptor UTS2R but through the activation of the somatostatin receptor (SSTR) 5. Circulating UTS2B concentrations in mice are physiologically regulated during starvation, further linking this peptide hormone to metabolism. Furthermore, administration of UTS2B to starved mice demonstrates that it is capable of regulating blood glucose and plasma concentrations of GLP-1 and insulin in vivo. Altogether, our results identify a novel cellular source of UTS2B in the gut, which acts in a paracrine manner to regulate GLP-1 secretion through SSTR5. These findings uncover a fine-tuning mechanism mediated by a ligand-receptor pair in the regulation of gut hormone secretion, which can potentially be exploited to correct metabolic unbalance caused by overactivation of the gut-pancreas axis.

Differential effects of passive immunization with somatostatin antiserum on adenohypophysial hormone secretions in starved rats

1986 ◽  
Vol 109 (2) ◽  
pp. 169-174 ◽  
Author(s):  
J. N. Hugues ◽  
A. Enjalbert ◽  
E. Moyse ◽  
C. Shu ◽  
M. J. Voirol ◽  
...  
Keyword(s):  
Binding Capacity ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Passive Immunization ◽  
Negative Control ◽  
Prolactin Secretion ◽  
Male Rats ◽  
Minimal Effective Dose ◽  
Gh Secretion

ABSTRACT The role of somatostatin (SRIF) on adenohypophysial hormone secretion in starved rats was reassessed by passive immunization. Because of the absence of pulsatile GH secretion in starved rats, the effects of the injection of SRIF antiserum on GH levels can be clearly demonstrated. To determine whether starvation modifies the sensitivity of the adenohypophysis to SRIF, we measured 125I-labelled iodo-N-Tyr-SRIF binding. There was no difference in the dissociation constant (Kd) nor in the maximal binding capacity (Bmax) in fed (n = 15) and starved (n = 15) animals (Kd = 0·38 ± 0·09 (s.e.m.) and 0·45 ± 0·09 nmol; Bmax = 204 ± 39 and 205 ± 30 fmol/mg protein respectively). Administration of SRIF antiserum resulted in a dose-dependent increase in plasma concentrations of GH, TSH and prolactin. The minimal effective dose of SRIF antiserum was 50 μl for GH, 100 μl for TSH and 200 μl for prolactin. Our results show that: (1) starvation does not modify adenohypophysial SRIF-binding sites, (2) in starved male rats endogenous SRIF exerts a negative control on prolactin secretion in vivo and (3) sensitivity to endogenous SRIF seems to be different for each hypophysial cell type. J. Endocr. (1986) 109, 169–174

Effects of metoclopramide on duodenal motility and flow events, glucose absorption, and incretin hormone release in response to intraduodenal glucose infusion

2010 ◽  
Vol 299 (6) ◽  
pp. G1326-G1333 ◽  
Author(s):  
Paul Kuo ◽  
Max Bellon ◽  
Judith Wishart ◽  
André J. Smout ◽  
Richard H. Holloway ◽  
...  
Keyword(s):  
Blood Glucose Concentration ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Glucose Absorption ◽  
Glucose Infusion ◽  
Pressure Waves ◽  
Incretin Hormone ◽  
Duodenal Motility ◽  
Glucagon Like Peptide 1 ◽  
Gip Release

The contribution of small intestinal motor activity to nutrient absorption is poorly defined. A reduction in duodenal flow events after hyoscine butylbromide, despite no change in pressure waves, was associated with reduced secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and a delay in glucose absorption. The aim of this study was to investigate the effect of metoclopramide on duodenal motility and flow events, incretin hormone secretion, and glucose absorption. Eight healthy volunteers (7 males and 1 female; age 29.8 ± 4.6 yr; body mass index 24.5 ± 0.9 kg/m2) were studied two times in randomized order. A combined manometry and impedance catheter was used to measure pressure waves and flow events in the same region of the duodenum simultaneously. Metoclopramide (10 mg) or control was administered intravenously as a bolus, followed by an intraduodenal glucose infusion for 60 min (3 kcal/min) incorporating the14C-labeled glucose analog 3- O-methylglucose (3-OMG). We found that metoclopramide was associated with more duodenal pressure waves and propagated pressure sequences than control ( P < 0.05 for both) during intraduodenal glucose infusion. However, the number of duodenal flow events, blood glucose concentration, and plasma 3-[14C]OMG activity did not differ between the two study days. Metoclopramide was associated with increased plasma concentrations of GLP-1 ( P < 0.05) and GIP ( P = 0.07) but lower plasma insulin concentrations ( P < 0.05). We concluded that metoclopramide was associated with increased frequency of duodenal pressure waves but no change in duodenal flow events and glucose absorption. Furthermore, GLP-1 and GIP release increased with metoclopramide, but insulin release paradoxically decreased.

Comparison of the feedback effect of magnesium and calcium on parathyroid hormone secretion in man

1987 ◽  
Vol 113 (1) ◽  
pp. 117-122 ◽  
Author(s):  
O. Ferment ◽  
P. E. Garnier ◽  
Y. Touitou
Keyword(s):  
Parathyroid Hormone ◽  
Urinary Excretion ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Magnesium Salt ◽  
Saline Injection ◽  
Molar Basis ◽  
Magnesium Salts ◽  
High Doses

ABSTRACT Administration of high doses of magnesium is known to produce a decrease in parathyroid hormone (PTH) secretion in human patients but the effect of magnesium on the secretion of PTH in healthy man is not known. We have looked at the effect of a relatively moderate i.v. dose of magnesium (7·08 mmol) in seven healthy men. In addition and for comparison the effect of calcium (4·25 mmol) was studied. Two magnesium salts were considered, magnesium sulphate (MgSO4) and magnesium pyrrolidone carboxylate (MgPC). Four i.v. injections were given at 08.00 h (MgPC, NaCl (control), MgSO4 and Ca gluconate), with an interval of 1 week between each injection. Whatever the magnesium salt the variations in plasma concentrations of magnesium were the same whereas no change in erythrocyte magnesium was observed. Plasma concentration of C-terminal PTH did not show significant variations after MgPC or saline injection. Both MgSO4 and Ca gluconate produced a statistically significant 30% decrease in plasma PTH levels 45 min after the injection. The effect was more sustained with calcium (2 h) than with magnesium (45 min). The urinary excretion of magnesium was significantly higher after injection of MgSO4 than after MgPC. These results suggest (1) that magnesium was, on a molar basis, less potent than calcium in regulating PTH secretion in vivo, (2) that the nature of the magnesium salt used must be kept in mind for the interpretation of the effect of magnesium on PTH secretion in vivo and (3) that the decrease in plasma PTH can partly explain the larger urinary excretion of magnesium after MgSO4 than after MgPC. J. Endocr. (1987) 113, 117–122

scholarly journals Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV suppresses meal-induced incretin secretion in dogs

2002 ◽  
Vol 172 (2) ◽  
pp. 355-362 ◽  
Author(s):  
CF Deacon ◽  
S Wamberg ◽  
P Bie ◽  
TE Hughes ◽  
JJ Holst
Keyword(s):  
Plasma Concentrations ◽  
Dipeptidyl Peptidase ◽  
Feedback Mechanism ◽  
Dipeptidyl Peptidase Iv ◽  
Biologically Active ◽  
Incretin Hormones ◽  
Dpp Iv ◽  
Incretin Secretion ◽  
Glucagon Like Peptide 1

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are degraded by dipeptidyl peptidase IV (DPP IV), thereby losing insulinotropic activity. DPP IV inhibition reduces exogenous GLP-1 degradation, but the extent of endogenous incretin protection has not been fully assessed, largely because suitable assays which distinguish between intact and degraded peptides have been unavailable. Using newly developed assays for intact GLP-1 and GIP, the effect of DPP IV inhibition on incretin hormone metabolism was examined. Conscious dogs were given NVP-DPP728, a specific DPP IV inhibitor, at a dose that inhibited over 90% of plasma DPP IV for the first 90 min following treatment. Total and intact incretin concentrations increased (P<0.0001) following a mixed meal, but on control days (vehicle infusion), intact peptide concentrations were lower (P<0.01) than total peptide concentrations (22.6 +/- 1.2% intact GIP; 10.1 +/- 0.4% intact GLP-1). Following inhibitor treatment, the proportion of intact peptide increased (92.5 +/- 4.3% intact GIP, P<0.0001; 99.0 +/- 22.6% intact GLP-1, P<0.02). Active (intact) incretins increased after NVP-DPP728 (from 4797 +/- 364 to 10 649 +/- 106 pM x min for GIP, P<0.03; from 646 +/- 134 to 2822 +/- 528 pM x m in for GLP-1, P<0.05). In contrast, total incretins fell (from 21 632 +/- 654 to 12 084 +/- 1723 pM x min for GIP, P<0.002; from 5145 +/- 677 to 3060 +/- 601 pM x min for GLP-1, P<0.05). Plasma glucose, insulin and glucagon concentrations were unaltered by the inhibitor. We have concluded that DPP IV inhibition with NVP-DPP728 prevents N-terminal degradation of endogenous incretins in vivo, resulting in increased plasma concentrations of intact, biologically active GIP and GLP-1. Total incretin secretion was reduced by DPP IV inhibition, suggesting the possibility of a feedback mechanism.

scholarly journals Cephalic phase secretion of insulin and other enteropancreatic hormones in humans

2016 ◽  
Vol 310 (1) ◽  
pp. G43-G51 ◽  
Author(s):  
Simon Veedfald ◽  
Astrid Plamboeck ◽  
Carolyn F. Deacon ◽  
Bolette Hartmann ◽  
Filip K. Knop ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Sham Feeding ◽  
C Peptide ◽  
Healthy Men ◽  
Glucose Levels ◽  
Gut Hormone ◽  
Cephalic Phase ◽  
Hormone Responses ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Enteropancreatic hormone secretion is thought to include a cephalic phase, but the evidence in humans is ambiguous. We studied vagally induced gut hormone responses with and without muscarinic blockade in 10 glucose-clamped healthy men (age: 24.5 ± 0.6 yr, means ± SE; body mass index: 24.0 ± 0.5 kg/m2; HbA1c: 5.1 ± 0.1%/31.4 ± 0.5 mmol/mol). Cephalic activation was elicited by modified sham feeding (MSF, aka “chew and spit”) with or without atropine (1 mg bolus 45 min before MSF + 80 ng·kg−1·min−1 for 2 h). To mimic incipient prandial glucose excursions, glucose levels were clamped at 6 mmol/l on all days. The meal stimulus for the MSF consisted of an appetizing breakfast. Participants (9/10) also had a 6 mmol/l glucose clamp without MSF. Pancreatic polypeptide (PP) levels rose from 6.3 ± 1.1 to 19.9 ± 6.8 pmol/l (means ± SE) in response to MSF and atropine lowered basal PP levels and abolished the MSF response. Neither insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), nor glucagon-like peptide-1 (GLP-1) levels changed in response to MSF or atropine. Glucagon and ghrelin levels were markedly attenuated by atropine prior to and during the clamp: at t = 105 min on the atropine (ATR) + clamp (CLA) + MSF compared with the saline (SAL) + CLA and SAL + CLA + MSF days; baseline-subtracted glucagon levels were −10.7 ± 1.1 vs. −4.0 ± 1.1 and −4.7 ± 1.9 pmol/l (means ± SE), P < 0.0001, respectively; corresponding baseline-subtracted ghrelin levels were 303 ± 36 vs. 39 ± 38 and 3.7 ± 21 pg/ml (means ± SE), P < 0.0001. Glucagon and ghrelin levels were unaffected by MSF. Despite adequate PP responses, a cephalic phase response was absent for insulin, glucagon, GLP-1, GIP, and ghrelin.

Effects of truncated glucagon-like peptide-1 on the responses of starved sheep to glucose

1991 ◽  
Vol 129 (1) ◽  
pp. 55-58 ◽  
Author(s):  
A. Faulkner ◽  
H. T. Pollock
Keyword(s):  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Amino Nitrogen ◽  
Insulin Response ◽  
Not Given ◽  
Glucose Load ◽  
Glucose Administration ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

ABSTRACT The effects of i.v. glucagon-like peptide-1-(7–36)amide (GLP-1; 10 μg) on starved sheep given an i.v. glucose load (5 g) were studied. Plasma insulin concentrations rose significantly more after glucose administration in fed than in starved sheep. Giving GLP-1 to starved sheep increased the insulin response to the glucose load. The rise in plasma insulin concentrations in starved sheep given GLP-1 was similar to that observed in fed sheep. Plasma glucose concentrations returned to normal values more quickly in the starved sheep given GLP-1 than in starved sheep not given gut hormone. Plasma concentrations of free fatty acid, urea and α-amino nitrogen decreased more quickly following glucose administration in starved sheep given GLP-1 than in those not given GLP-1. The data suggest a role for GLP-1 in regulating plasma insulin concentrations and hence metabolism in ruminant animals. The possible role of gut hormones in ruminants is discussed. Journal of Endocrinology (1991) 129, 55–58

scholarly journals Gastrointestinal Motility and Gut Hormone Secretion in response to Shenhuang Plaster in a Postoperative Ileus Rat Model

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yanan Shi ◽  
Yingsong Zheng ◽  
Jingming Xu ◽  
Bin Ding ◽  
Qiyang Shou ◽  
...  
Keyword(s):  
Gastrointestinal Motility ◽  
Postoperative Ileus ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
Gastrointestinal Transit ◽  
Gastrointestinal Function ◽  
Sprague Dawley ◽  
Ghrelin Concentration ◽  
Intestinal Hormones ◽  
Gut Hormone

Postoperative ileus (POI), a gastrointestinal function disorder, is a complication that arises from surgery. Shenhuang plaster (SHP) application to the Shenque acupoint (CV8) to promote the recovery of gastrointestinal function has achieved definite curative effects in clinical settings; however, the underlying pharmacological mechanism remains unknown. In this study, we evaluated the effects of SHP using a Sprague Dawley rat POI model. Then, gastrointestinal transit in different rat groups was evaluated by the movement of fluorescein-labelled dextran. Ghrelin, obestatin, motilin (MTL), and vasoactive intestinal peptide (VIP) plasma concentrations were measured via a radioimmunoassay. The expression of the ghrelin and obestatin receptors (GHS-R1α and GPR39) in the intestinal muscularis of rats in different groups was comparatively identified via western blotting. The results indicated that SHP application improved gastrointestinal motility in POI model rats. SHP application significantly increased ghrelin concentration and the expression of its receptor and inhibited obestatin concentration and the expression of its receptor in blood. Further, ghrelin concentration and the capability of gastrointestinal transit were positively correlated. Simultaneously, SHP application also promoted the secretion of other gastrointestinal motility hormones, such as MTL and VIP. Hence, these results provide evidence that SHP can promote the recovery of gastrointestinal transmission in POI rat models through regulation of ghrelin and other intestinal hormones.

scholarly journals Dynamic Changes in Function and Proteomic Composition of Extracellular Vesicles from Hepatic Stellate Cells during Cellular Activation

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 290 ◽  
Author(s):  
Xinlei Li ◽  
Ruju Chen ◽  
Sherri Kemper ◽  
David R Brigstock
Keyword(s):  
Gene Expression ◽  
Hepatic Stellate Cells ◽  
Fold Increase ◽  
Stellate Cells ◽  
Extracellular Vesicle ◽  
Fine Tuning ◽  
Shared Identity ◽  
Cellular Source

During chronic liver injury, hepatic stellate cells (HSC) undergo activation and are the principal cellular source of collagenous scar. In this study, we found that activation of mouse HSC (mHSC) was associated with a 4.5-fold increase in extracellular vesicle (EV) production and that fibrogenic gene expression (CCN2, Col1a1) was suppressed in Passage 1 (P1; activated) mHSC exposed to EVs from Day 4 (D4; relatively quiescent) mHSC but not to EVs from P1 mHSC. Conversely, gene expression (CCN2, Col1a1, αSMA) in D4 mHSC was stimulated by EVs from P1 mHSC but not by EVs from D4 mHSC. EVs from Day 4 mHSC contained only 46 proteins in which histones and keratins predominated, while EVs from P1 mHSC contained 337 proteins and these were principally associated with extracellular spaces or matrix, proteasome, collagens, vesicular transport, metabolic enzymes, ribosomes and chaperones. EVs from the activated LX-2 human HSC (hHSC) line also promoted fibrogenic gene expression in D4 mHSC in vitro and contained 524 proteins, many of which shared identity or had functional overlap with those in P1 mHSC EVs. The activation-associated changes in production, function and protein content of EVs from HSC likely contribute to the regulation of HSC function in vivo and to the fine-tuning of fibrogenic pathways in the liver.

Secretion and gene expression of inhibin, oxytocin and steroid hormones during the in vitro differentiation of bovine granulosa cells

1990 ◽  
Vol 2 (1) ◽  
pp. 11 ◽  
Author(s):  
MR Luck ◽  
RJ Rodgers ◽  
JK Findlay
Keyword(s):  
Granulosa Cells ◽  
Cultured Cells ◽  
Hormone Secretion ◽  
Peptide Hormone ◽  
Northern Analysis ◽  
Messenger Rnas ◽  
Defined Culture ◽  
Hormone Secretions

Bovine granulosa cells were cultured under defined conditions to examine (1) their secretion of immunoreactive inhibin, oxytocin, progesterone and oestradiol during differentiation in vitro; (2) their expression, by Northern analysis, of specific mRNAs for inhibin and oxytocin as compared with uncultured cells; (3) possible interrelationships between the four secreted hormones; and (4) the hypothesis that androgens and steroidogenesis influence the secretion of inhibin. The secretion of inhibin and oestradiol fell rapidly over the first few days of culture but remained at detectable levels for at least 7 days. Conversely, the secretion of oxytocin and progesterone rose steadily as culture progressed. These changes occurred spontaneously (i.e. without gonadotrophin treatment) and were not dependent on the addition of serum to the culture medium. Messenger RNAs for the inhibin alpha- and beta A-subunits were present in uncultured cells but barely detectable or undetectable in cells cultured for 4 days. Conversely, the mRNA for oxytocin, which was not detectable in uncultured cells, was present in cultured cells and increased in quantity as culture progressed. Treatment of cells with testosterone (5 nM-5 microM), in the presence or absence of serum (10% FCS), had no effect on the secretion of inhibin but stimulated the declining oestradiol secretion. Treatment with ascorbic acid (0.5 mM) increased the secretion of oxytocin and progesterone, as previously described, but not that of inhibin. Treatment with aminoglutethimide (0.5 mM), an inhibitor of steroidogenesis, substantially inhibited progesterone secretion and the response of oestradiol secretion to testosterone, but had no effect on the secretion of either inhibin or oxytocin. We conclude that bovine granulosa cells differentiate spontaneously in defined culture in a manner that, as defined by the secretion of steroid and peptide hormones, closely resembles their luteinization in vivo. The switch in protein hormone secretion from inhibin to oxytocin is accompanied by a corresponding change in mRNA expression. The changes in steroid and peptide hormone secretions that take place in culture appear to occur independently of one another although their absolute cause remains to be determined. In contrast to previous studies, we could find no evidence for the regulation of inhibin secretion by either androgens or steroidogenesis.

scholarly journals Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets

2010 ◽  
Vol 162 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Solrun Vidarsdottir ◽  
Ferdinand Roelfsema ◽  
Trea Streefland ◽  
Jens J Holst ◽  
Jens F Rehfeld ◽  
...  
Keyword(s):  
Weight Gain ◽  
Peptide Yy ◽  
Hormone Secretion ◽  
Gut Hormones ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Healthy Men ◽  
Gut Hormone ◽  
Glucagon Like Peptide 1

BackgroundTreatment with olanzapine (atypical antipsychotic drug) is frequently associated with various metabolic anomalies, including obesity, dyslipidemia, and diabetes mellitus. Recent data suggest that olanzapine orally disintegrating tablets (ODT), which dissolve instantaneously in the mouth, might cause less weight gain than olanzapine standard oral tablets (OST).Design and methodsTen healthy men received olanzapine ODT (10 mg o.d., 8 days), olanzapine OST (10 mg o.d., 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, blood samples were taken for measurement of pancreatic polypeptide, peptide YY, glucagon-like peptide-1, total glucagon, total ghrelin, and cholecystokinin (CCK) concentrations.ResultsWith the exception of pre- and postprandial concentration of ghrelin at dinner and preprandial CCK concentrations at breakfast, which were all slightly increased (respectivelyP=0.048,P=0.034 andP=0.042), olanzapine did not affect gut hormone concentrations. Thus, olanzapine ODT and OST had similar effects on gut hormone secretion.ConclusionShort-term treatment with olanzapine does not have major impact on the plasma concentration of gut hormones we measured in healthy men. Moreover, despite pharmacological difference, gut hormone concentrations are similar during treatment with olanzapine ODT and OST. The capacity of olanzapine to induce weight gain and diabetes is unlikely to be caused by modulation of the secretion of gut hormones measured here. We cannot exclude the possibility that olanzapine's impact on other gut hormones, to impair insulin sensitivity and stimulate weight gain, exists.

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