Effect of exenatide once-weekly (QW) on gastric emptying in health: impact on glycaemia and glucose absorption

International audienceBackground and aims: ‘Short-acting’ glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) lower postprandial glucose predominantly via their profound effect to slow gastric emptying (GE). It is generally assumed that ‘long-acting’ GLP-1RAs have little, if any, effect on GE with longer-term administration, reflecting ‘tachyphylaxis’ to slowing of GE as a result of sustained receptor exposure. However, information relating to the effect of ‘long-acting’ GLP-1RAs on GE is limited and previous studies have been compromised by the use of suboptimal methodology to quantify GE. We evaluated the effects of 8 weeks’ administration of exenatide once-weekly (ExQW) on GE of solids and liquids (using the ‘gold standard’ technique, scintigraphy), postprandial glycaemia and glucose absorption in health. Materials and methods: Thirty two healthy participants completed an 8-week double-blind, placebo-controlled, parallel-group designed study. Participants were randomised to receive either ExQW (2mg sc) (6M, 10F; mean age: 59.9 ± 0.9yr; BMI: 29.6 ± 0.6 kg/m2) or matched placebo (PLAC) (6M, 10F; mean age: 60.6 ± 1.2yr; BMI: 29.5 ± 1.0 kg/m2). GE, nausea (100mm visual analogue scale) and plasma glucose, insulin, C-peptide, glucagon were measured for 120 min after a mixed solid/liquid meal, comprising 100g minced beef radiolabelled with 20MBq 99mTc-sulphur colloid and 150ml 10% glucose radiolabelled with 7MBq 67Ga-EDTA and containing 5g 3-O-methyl-glucose (3-OMG) to assess oral glucose absorption, at baseline and after 8 weeks’ administration. Data are shown as mean values ± SEM and a PResults: The studies were well-tolerated. Scores for nausea were consistently very low and there was no difference between ExQW and PLAC groups at either baseline or after treatment. ExQW slowed GE of both solids (AUC0-120: P=0.05) and liquids (AUC0-120: P=0.01) substantially (Figure) and attenuated both the postprandial rise in plasma glucose (e.g. iAUC0-30: P=0.008) and glucose absorption (e.g. 3-OMG iAUC0-30: P=0.001). There were no differences in plasma insulin, C-peptide or glucagon between the two groups. The magnitude of the reduction in plasma glucose at t=30 min from baseline to 8 weeks with ExQW was inversely related to the 50% emptying time of the glucose drink (r=-0.55, P=0.03) i.e. postprandial glucose-lowering by ExQW was dependent on the magnitude of the slowing of GE. Conclusion: In healthy subjects, 8 weeks administration of the ‘long-acting’ GLP-1RA, ExQW, slows GE of solids and liquids with consequent reductions in glucose absorption and postprandial glycaemia

Effects of a guar/whey preload on gastric emptying and glycaemic responses to oral glucose in healthy older people

International audienceBackground and aims: A whey protein/guar preload (Omniblend Innovation) has been developed recently to reduce postprandial glycaemia. The preload comprises 5g guar, 20g (whey) protein and 3g lactose (total 90kcal) in a sachet, which is added to a ‘shake and take’ cup containing 150ml water. Our previous trial suggested that this supplement slowed gastric emptying (GE), but the latter was assessed using a stable isotope breath test technique which limits the capacity to discriminate between slowing of GE and a delay in intestinal absorption. Our aim was to determine the effects of this guar/whey protein preload on GE (using the ‘gold standard’ technique, scintigraphy), and the glycaemic/ insulinaemic responses to an oral glucose load in healthy older people. Materials and methods: Ten healthy older participants (6F, 4M; age: 74.0 ± 1.6 yr; BMI: 26.0 ± 0.7 kg/m2) with normal glucose tolerance underwent concurrent measurements of GE, plasma glucose and insulin for 180 min on two occasions. Participants were studied after an overnight fast, were seated with their back against a gamma camera and a cannula inserted into an antecubital vein for blood sampling. In random order, each received a test drink comprising 50g glucose made up to 300ml with water containing 20MBq 99mTc-calcium-phytate with or without the guar/whey protein preload (90kcal) made up to 150ml with water, ingested 15 min before the test drink. Blood samples were taken immediately before the preload, before the glucose test drink and at 15-30 min intervals thereafter until t=180 min. The early insulin secretory response was estimated by the ratio of the change in insulin (ΔI0-30) to that of glucose at 30 min (ΔG0-30) represented as ΔI0-30/ΔG0-30. Data are mean values ± SEM. Results: The guar/whey protein preload reduced both the iAUC0-120 (PConclusion: In healthy older people, the glucose-lowering effect of the whey protein/guar preload appears unrelated to changes in GE and may reflect increased insulin secretion and/or slowing of small intestinal absorption

Exenatide once weekly slows gastric emptying of solids and liquids in healthy, overweight, subjects under steady-state concentrations

AIMS: To evaluate the effects of 8 weeks' administration of exenatide once-weekly (ExQW) on gastric emptying of solids and liquids (using the 'gold standard' technique, scintigraphy), glucose absorption and postprandial glycaemia in health. MATERIAL AND METHODS: Thirty two healthy participants were randomized to receive ExQW (2mg per week subcutaneously) (6M,10F; age: 59.9±0.9 yr; BMI: 29.6±0.6 kg/m2 ) or matching placebo (PLAC) (6M,10F; age: 60.6±1.2 yr; BMI: 29.5±1.0 kg/m2 ) for 8 weeks. Gastric emptying, nausea (visual analog scale), and plasma glucose, insulin, C-peptide and glucagon were measured for 120min after a solid/liquid meal, comprising 100g ground beef (radiolabelled with 20MBq 99m Tc-sulphur colloid) and 150ml 10% glucose (radiolabelled with 7MBq 67 Ga-EDTA), and containing 5g 3-O-methyl-glucose (3-OMG) as a marker of glucose absorption, at baseline and after 8 weeks' treatment. RESULTS: The studies were well tolerated. Scores for nausea were consistently low without any difference between ExQW and PLAC groups. ExQW slowed gastric emptying of solids (e.g. AUC 0-120min: P<0.05) and liquids (e.g. AUC 0-120min: P=0.01) substantially and attenuated glucose absorption (e.g. 3-OMG iAUC 0-30min: P=0.001) and the postprandial rise in plasma glucose (e.g. iAUC 0-30min: P=0.008). Plasma glucagon at 2h was reduced by ExQW (P=0.001). The magnitude of the reduction in plasma glucose at t=30min from baseline to 8 weeks with ExQW was related inversely to the 50% emptying time of the glucose drink (r=-0.55, P=0.03). CONCLUSIONS: In healthy subjects, 8 weeks administration of the 'long-acting' GLP-1RA, ExQW, slows gastric emptying of solids and liquids substantially, with consequent reductions in glucose absorption and postprandial glycaemia. Clinical Trials Registration Number: ACTRN 12616000955415 This article is protected by copyright. All rights reserved.Karen L. Jones, Christopher K. Rayner, Michael Horowitz, Tongzhi Wu, Rachael S. Rigda, iza K. Phillips ... et al

Evaluation of organ distribution of microcystins in the freshwater phytoplanktivorous fish Hypophthalmichthys molitrix

To evaluate the public health risk of exposure to microcystins in fish food in China, the distribution pattern of microcystin-LR and microcystin-RR in various organs (liver, intestine, kidney, muscle and lipid) of the dominant freshwater phytoplanktivorous fish Hypophthalmichthys molitrix in Hangzhou, China’s Tiesha River was investigated with the method of HPLC-ESI-MS analysis. The distribution of microcystins was different in the fish organs and the major total microcystins (microcystin-LR and microcystin-RR) were present in the intestines (6.49 μg/g fresh weight), followed by the livers (4.52 μg/g fresh weight) and the muscles (2.86 μg/g fresh weight). Microcystins were detected in kidneys (1.35 μg/g fresh weight), but not detected in lipid. The results suggested that the mean daily intake from fish was 0.03 μg/kg body weight which was very close to the recommended WHO tolerable daily intake (TDI) level of 0.04 μg/kg body weight per day, and local people were warned they may have health risk if they consumed fish from the river

The Large High Altitude Air Shower Observatory (LHAASO) Science White Paper

The Large High Altitude Air Shower Observatory (LHAASO) project is a new generation multi-component instrument, to be built at 4410 meters of altitude in the Sichuan province of China, with the aim to study with unprecedented sensitivity the spec trum, the composition and the anisotropy of cosmic rays in the energy range between 10$^{12}$ and 10$^{18}$ eV, as well as to act simultaneously as a wide aperture (one stereoradiant), continuously-operated gamma ray telescope in the energy range between 10$^{11}$ and $10^{15}$ eV. The experiment will be able of continuously surveying the TeV sky for steady and transient sources from 100 GeV to 1 PeV, t hus opening for the first time the 100-1000 TeV range to the direct observations of the high energy cosmic ray sources. In addition, the different observables (electronic, muonic and Cherenkov/fluorescence components) that will be measured in LHAASO will allow to investigate origin, acceleration and propagation of the radiation through a measurement of energy spec trum, elemental composition and anisotropy with unprecedented resolution. The remarkable sensitivity of LHAASO in cosmic rays physics and gamma astronomy would play a key-role in the comprehensive general program to explore the High Energy Universe. LHAASO will allow important studies of fundamental physics (such as indirect dark matter search, Lorentz invariance violation, quantum gravity) and solar and heliospheric physics. In this document we introduce the concept of LHAASO and the main science goals, providing an overview of the project

The Large High Altitude Air Shower Observatory (LHAASO) Science Book (2021 Edition)

International audienceSince the science white paper of the Large High Altitude Air Shower Observatory (LHAASO) published on arXiv in 2019 [e-Print: 1905.02773 (astro-ph.HE)], LHAASO has completed the transition from a project to an operational gamma-ray astronomical observatory LHAASO is a new generation multi-component facility located in Daocheng, Sichuan province of China, at an altitude of 4410 meters. It aims at measuring with unprecedented sensitivity the spectrum, composition, and anisotropy of cosmic rays in the energy range between 10$^{12}$ and 10$^{18}$~eV, and acting simultaneously as a wide aperture (one stereoradiant) continuously operating gamma-ray telescope in the energy range between 10$^{11}$ and $10^{15}$~eV with the designed sensitivity of 1.3% of the Crab Unit (CU) above 100 TeV. LHAASO's capability of measuring simultaneously different shower components (electrons, muons, and Cherenkov/fluorescence light), will allow it to investigate the origin, acceleration, and propagation of CR through measurement of the energy spectrum, elemental composition, and anisotropy with unprecedented resolution. The remarkable sensitivity of LHAASO will play a key role in CR physics and gamma-ray astronomy for a general and comprehensive exploration of the high energy universe and will allow important studies of fundamental physics (such as indirect dark matter search, Lorentz invariance violation, quantum gravity) and solar and heliospheric physics. The LHAASO Collaboration organized an editorial working group and finished all editorial work of this science book, to summarize the instrumental features and outline the prospects of scientific researches with the LHAASO experiment

The Large High Altitude Air Shower Observatory (LHAASO) Science White Paper

The Large High Altitude Air Shower Observatory (LHAASO) project is a new generation multi-component instrument, to be built at 4410 meters of altitude in the Sichuan province of China, with the aim to study with unprecedented sensitivity the spec trum, the composition and the anisotropy of cosmic rays in the energy range between 10$^{12}$ and 10$^{18}$ eV, as well as to act simultaneously as a wide aperture (one stereoradiant), continuously-operated gamma ray telescope in the energy range between 10$^{11}$ and $10^{15}$ eV. The experiment will be able of continuously surveying the TeV sky for steady and transient sources from 100 GeV to 1 PeV, t hus opening for the first time the 100-1000 TeV range to the direct observations of the high energy cosmic ray sources. In addition, the different observables (electronic, muonic and Cherenkov/fluorescence components) that will be measured in LHAASO will allow to investigate origin, acceleration and propagation of the radiation through a measurement of energy spec trum, elemental composition and anisotropy with unprecedented resolution. The remarkable sensitivity of LHAASO in cosmic rays physics and gamma astronomy would play a key-role in the comprehensive general program to explore the High Energy Universe. LHAASO will allow important studies of fundamental physics (such as indirect dark matter search, Lorentz invariance violation, quantum gravity) and solar and heliospheric physics. In this document we introduce the concept of LHAASO and the main science goals, providing an overview of the project