Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults

2007 ◽  
Vol 292 (5) ◽  
pp. G1359-G1365 ◽  
Author(s):  
Christopher N. Andrews ◽  
Adil E. Bharucha ◽  
Michael Camilleri ◽  
Phillip A. Low ◽  
Barbara Seide ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
Photon Emission ◽  
Gastric Volume ◽  
Emission Computed Tomography ◽  
High Dose ◽  
Double Blind Study ◽  
Vagal Activity ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin glucagon-like peptide-1 (GLP-1), which is used to treat diabetes mellitus, delays gastric emptying by inhibiting vagal activity. GLP-1 also increases fasting and postprandial gastric volume in humans. On the basis of animal studies, we hypothesized that nitric oxide mediates the effects of GLP-1 on gastric volumes. To assess the effects of nitrergic blockade on GLP-1-induced gastric accommodation in humans, in this double-blind study, 31 healthy volunteers were randomized to placebo (i.e., saline), GLP-1, or the nitric oxide synthase inhibitor NG-monomethyl-l-arginine acetate (l-NMMA; 4 mg·kg−1·h−1) alone or with GLP-1. Thereafter, 16 additional subjects were randomized to GLP-1 alone or together with a higher dose of l-NMMA (10 mg/kg bolus plus 8 mg·kg−1·h−1 infusion). Gastric volumes (fasting pre- and postdrug, postprandial postdrug) were measured by 99mTc-single-photon-emission computed tomography imaging. GLP-1 increased ( P = 0.04) fasting gastric volume by 83 ± 16 ml (vs. 17 ± 11 ml for placebo) and augmented ( P ≤ 0.01) postprandial accommodation by 688 ± 165 ml (vs. 542 ± 29 ml for placebo). l-NMMA (low dose) alone did not affect fasting or postprandial gastric volume. l-NMMA (low dose) did not attenuate the effect of GLP-1 on gastric volumes. In contrast, l-NMMA (high dose) did not affect fasting volume but blunted GLP-1-mediated postprandial accommodation (postprandial change = 494 ± 37 ml, P ≤ 0.01 vs. GLP-1 alone). These data are consistent with the hypothesis that nitric oxide partly mediates the effects of GLP-1 on postprandial but not fasting gastric volumes in humans.

scholarly journals The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution

2019 ◽  
Vol 240 (2) ◽  
pp. 271-286 ◽  
Author(s):  
Li Zhao ◽  
Chunfang Zhu ◽  
Meng Lu ◽  
Chi Chen ◽  
Xiaomin Nie ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Body Fat ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Control Group ◽  
Acid Oxidation ◽  
High Dose ◽  
Fat Depots ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an ideal therapy for type 2 diabetes and, as of recently, for obesity. In contrast to visceral fat, subcutaneous fat appears to be protective against metabolic diseases. Here, we aimed to explore whether liraglutide, a GLP-1RA, could redistribute body fat via regulating lipid metabolism in different fat depots. After being fed a high-fat diet for 8 weeks, 50 male Wistar and Goto-Kakizaki rats were randomly divided into a normal control group, a diabetic control group, low- and high-dose liraglutide-treated groups and a diet-control group. Different doses of liraglutide (400 μg/kg/day or 1200 μg/kg/day) or an equal volume of normal saline were administered to the rats subcutaneously once a day for 12 weeks. Body composition and body fat deposition were measured by dual-energy X-ray absorptiometry and MRI. Isotope tracers were infused to explore lipid metabolism in different fat depots. Quantitative real-time PCR and Western blot analyses were conducted to evaluate the expression of adipose-related genes. The results showed that liraglutide decreased visceral fat and relatively increased subcutaneous fat. Lipogenesis was reduced in visceral white adipose tissue (WAT) but was elevated in subcutaneous WAT. Lipolysis was also attenuated, and fatty acid oxidation was enhanced. The mRNA expression levels of adipose-related genes in different tissues displayed similar trends after liraglutide treatment. In addition, the expression of browning-related genes was upregulated in subcutaneous WAT. Taken together, the results suggested that liraglutide potentially redistributes body fat and promotes browning remodeling in subcutaneous WAT to improve metabolic disorders.

Multiple low-dose and single high-dose treatments with streptozotocin do not generate nitric oxide

2000 ◽  
Vol 77 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Gianpaolo Papaccio ◽  
Francesco Aurelio Pisanti ◽  
Michael V.G. Latronico ◽  
Eduardo Ammendola ◽  
Michela Galdieri
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
High Dose ◽  
Single High Dose

Development of a test to measure gastric accommodation in humans

1999 ◽  
Vol 277 (6) ◽  
pp. G1217-G1221 ◽  
Author(s):  
Sjoerd D. Kuiken ◽  
Melvin Samsom ◽  
Michael Camilleri ◽  
Brian P. Mullan ◽  
Duane D. Burton ◽  
...  
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Gastric Volume ◽  
Emission Computed Tomography ◽  
Gastric Accommodation ◽  
Distal Stomach ◽  
Tomographic Images ◽  
Coefficients Of Variation ◽  
Health And Disease

Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of99mTc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 ± 11 (SE) ml and mean postprandial volume was 690 ± 32 ml ( P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.

Semaglutide in Cystic Fibrosis-Related Diabetes

2020 ◽  
Vol 105 (7) ◽  
pp. 2341-2344
Author(s):  
Helen Gnanapragasam ◽  
Naghma Mustafa ◽  
Mary Bierbrauer ◽  
Tara Andrea Providence ◽  
Paresh Dandona
Keyword(s):  
Cystic Fibrosis ◽  
Basal Insulin ◽  
Low Dose ◽  
Pancreatic Enzyme ◽  
Glucose Monitoring ◽  
Prandial Insulin ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
And Control ◽  
Mean Glucose

Abstract Context and Objective In spite of the evidence that inadequately controlled glycemia is associated with worse clinical outcomes, cystic fibrosis-related diabetes (CFRD) is not well controlled in a majority of patients. The objective of this report is to demonstrate the effect of the addition of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), to basal insulin to control glycemia in one such patient. Design, Intervention, and the Main Outcome Measures The replacement of rapidly acting prandial insulin with semaglutide weekly with continuation of basal insulin. Glycated hemoglobin A1c (HbA1c) was measured and continuous glucose monitoring (CGM) was conducted. Results There was a significant improvement in glycemic control, reduction in HbA1c from 9.1% to 6.7% and stable euglycemic pattern on CGM (mean glucose, 142 mg/dL; SD, 51) within 3 months of starting treatment. There was no increase in plasma pancreatic enzyme concentrations. Conclusions Semaglutide at a low dose was able to replace prandial insulin and control glycemia in combination with basal insulin.

Sign in / Sign up

Export Citation Format

Share Document