scholarly journals Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects

2004 ◽  
Vol 91 (3) ◽  
pp. 439-446 ◽  
Author(s):  
Erik Näslund ◽  
N. King ◽  
S. Mansten ◽  
N. Adner ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Emptying ◽  
Food Intake ◽  
Double Blind ◽  
Gastric Emptying Rate ◽  
Subcutaneous Injections ◽  
Subcutaneous Infusion ◽  
Continuous Subcutaneous Infusion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Recombinant glucagon-like peptide-1 (7–36)amide (rGLP-1) was recently shown to cause significant weight loss in type 2 diabetics when administered for 6 weeks as a continuous subcutaneous infusion. The mechanisms responsible for the weight loss are not clarified. In the present study, rGLP-1 was given for 5d by prandial subcutaneous injections (PSI) (76nmol 30min before meals, four times daily; a total of 302·4nmol/24h) or by continuous subcutaneous infusion (CSI) (12·7nmol/h; a total of 304·8nmol/24h). This was performed in nineteen healthy obese subjects (mean age 44·2 (sem 2·5) years; BMI 39·0 (sem 1·2)kg/m2) in a prospective randomised, double-blind, placebo-controlled, cross-over study. Compared with the placebo, rGLP-1 administered as PSI and by CSI generated a 15% reduction in mean food intake per meal (P=0·02) after 5d treatment. A weight loss of 0·55 (sem 0·2) kg (P<0·05) was registered after 5d with PSI of rGLP-1. Gastric emptying rate was reduced during both PSI (P<0·001) and CSI (P<0·05) treatment, but more rapidly and to a greater extent with PSI of rGLP-1. To conclude, a 5d treatment of rGLP-1 at high doses by PSI, but not CSI, promptly slowed gastric emptying as a probable mechanism of action of increased satiety, decreased hunger and, hence, reduced food intake with an ensuing weight loss.

scholarly journals Ghrelin Stimulates Gastric Emptying and Hunger in Normal-Weight Humans

2006 ◽  
Vol 91 (9) ◽  
pp. 3296-3302 ◽  
Author(s):  
F. Levin ◽  
T. Edholm ◽  
P. T. Schmidt ◽  
P. Grybäck ◽  
H. Jacobsson ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Peptide Yy ◽  
Hormone Secretion ◽  
Normal Weight ◽  
Lag Phase ◽  
Double Blind ◽  
Gastric Emptying Rate ◽  
Ghrelin Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Context: Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. Main Objective: The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion in normal volunteers. Design: This was a randomized, double-blind, crossover study. Subjects: Subjects included normal human volunteers and patients with GH deficiency. Intervention: Intervention included saline or ghrelin (10 pmol/kg·min) infusion for 180 min after intake of a radioactively labeled omelette (310 kcal) or GH substitution in GH-deficient patients. Main Outcome Measures: Measures consisted of gastric empty-ing parameters and postprandial plasma levels of ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY, and motilin. Results: The emptying rate was significantly faster for ghrelin (1.26 ± 0.1% per minute), compared with saline (0.83% per minute) (P &lt; 0.001). The lag phase (16.2 ± 2.2 and 26.5 ± 3.8 min) and half-emptying time (49.4 ± 3.9 and 75.6 ± 4.9 min) of solid gastric emptying were shorter during ghrelin infusion, compared with infusion of saline (P &lt; 0.001). The postprandial peak in plasma concentration for cholecystokinin and glucagon-like peptide-1 occurred earlier and was higher during ghrelin infusion. There was no significant effect of ghrelin on plasma motilin or peptide YY. There was no difference in gastric emptying before and after GH substitution. Conclusion: Our results demonstrate that ghrelin increases the gastric emptying rate in normal humans. The effect does not seem to be mediated via GH or motilin but may be mediated by the vagal nerve or directly on ghrelin receptors in the stomach. Ghrelin receptor agonists may have a role as prokinetic agents.

scholarly journals Glucagon Like Peptide 1 and Evidence Around Diabetes Specific Nutrition

2019 ◽  
Vol 10 (2) ◽  
pp. 64-75
Author(s):  
ANSHU JOSHI ◽  
SAMEER RAO ◽  
GANESH KADHE
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Gastric Emptying ◽  
Food Intake ◽  
Diabetes Management ◽  
Monounsaturated Fatty Acids ◽  
Complex Carbohydrate ◽  
Soluble Fibre ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

There has been significant research and development in pharmaco-therapeutic molecules for management of type 2 diabetes mellitus (T2DM). Diabetes specific nutrition intervention & newer incretin-based therapies have gained a lot of attention. Since incretins play an essential role in augmenting the post-prandial release of insulin, it is important to understand the science behind incretins and modulation of same by diabetic-specific nutrition (DSN). The purpose of this article is to summarize the available science around glucagon like peptide 1 (GLP-1) and the known role of nutrition, particularly diabetes specific nutrition. Literature published in PubMed, Google scholar and Embase were studied up to the end of August 2018. The key words of GLP-1, T2DM and Nutrients were used in different combinations. It was found that macronutrient aspects of DSN like complex carbohydrate, soluble fibre, proteins and high monounsaturated fatty acids augment GLP-1 secretion from intestinal L-cells. This may be attributed to insulin-trophic effects of DSN as well as its effects in causing deceleration in gastric emptying and reducing food intake. Hence, it was concluded that augmenting GLP-1 secretion in response to the intake of certain nutrients helps in modulating insulin secretion, metabolic homeostasis as well as decelerating gastric emptying and reducing food intake. DSN increases endogenous GLP-1 secretion which in turn improves insulin secretion and sensitivity. Thus, integrating DSN in mainstay diabetes management plans may result in better glycaemic and metabolic controls, particularly when GLP-1 based therapies are concurrently in use. Key Messages: DSN containing complex carbohydrate, soluble fibre, proteins and high monounsaturated fatty acids (MUFAs) augments GLP-1 secretion which in turn improves insulin secretion and sensitivity.

ONE MONTH WEIGHT LOSS PREDICTS THE EFFICACY OF LIRAGLUTIDE IN OBESE PATIENTS: DATA FROM A SINGLE CENTER

2020 ◽  
Vol 26 (2) ◽  
pp. 235-240 ◽  
Author(s):  
Carla Maccora ◽  
Cristina Ciuoli ◽  
Arianna Goracci ◽  
Nicoletta Benenati ◽  
Caterina Formichi ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Weight Loss ◽  
Food Intake ◽  
Body Mass ◽  
Receptor Agonist ◽  
Smoking Habit ◽  
Early Response ◽  
Significant Weight Loss ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Objective: Liraglutide is a glucagon-like peptide 1 receptor agonist which acts through peripheral and central receptor pathways affecting food intake. Preliminary identification of responder patients represents a crucial point to reduce an inappropriate exposure to the drug and the health expenditure. The primary endpoint of our study was to identify predictors of liraglutide efficacy in the short term follow-up. The secondary endpoint was to evaluate the treatment efficacy stratified by the underlying psychiatric disorder. Methods: We evaluated a cohort of 100 patients (77 females, 23 males, mean body mass index 38.6 ± 3.2 kg/m2) who were evaluated at baseline, and after 1, 3, and 6 months of treatment. Liraglutide efficacy was defined by a weight loss ≥5% of initial weight. Sociodemographic/metabolic parameters, food intake, smoking habit, and physical activity were correlated with liraglutide efficacy. Results: There was a significant weight loss after 1 month of therapy, as well as after 3 and 6 months when compared to the baseline ( P<.0001; 27%, 45%, and 57% of patients showed a weight loss ≥5%, respectively). No difference was found in weight loss between the 3 groups of patients (with binge eating, with/without psychiatric disorders). The weight loss at 1 month was the only predictor of a positive response to the treatment. Conclusion: Our results confirm the efficacy of liraglutide even at a lower dose than conventional. The early response to the drug seems to be a good predictor of long-term efficacy and it might be useful in clinical practice to identify patients in whom liraglutide may induce a significant weight loss. Abbreviations: BMI = body mass index; EMA = European Medicine Agency; FDA = Food and Drug Administration; GLP-1 RA = glucagon-like peptide 1 receptor agonist

scholarly journals The Glucagon-Like Peptide-1 Receptor Agonist Oxyntomodulin Enhances β-Cell Function but Does Not Inhibit Gastric Emptying in Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5670-5678 ◽  
Author(s):  
Adriano Maida ◽  
Julie A. Lovshin ◽  
Laurie L. Baggio ◽  
Daniel J. Drucker
Keyword(s):  
Blood Glucose ◽  
Amino Acid ◽  
Gastric Emptying ◽  
Food Intake ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Glucose Administration ◽  
Amino Acid Peptide ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The proglucagon gene gives rise to multiple peptides that play diverse roles in the control of energy intake, gut motility, and nutrient disposal. Glucagon-like peptide-1 (GLP-1), a 30-amino-acid peptide regulates glucose homeostasis via control of insulin and glucagon secretion and by inhibition of gastric emptying and food intake. Oxyntomodulin (OXM) a 37-amino-acid peptide also derived from the proglucagon gene, binds to both the glucagon and GLP-1 receptor (GLP-1R); however, a separate OXM receptor has not yet been identified. Here we show that OXM, like other GLP-1R agonists, stimulates cAMP formation and lowers blood glucose after both oral and ip glucose administration, actions that require a functional GLP-1R. OXM also directly stimulates insulin secretion from murine islets and INS-1 cells in a glucose- and GLP-1R-dependent manner. Moreover, OXM ameliorates hyperglycemia and significantly reduces apoptosis in murine β-cells after streptozotocin administration and directly reduces apoptosis in thapsigargin-treated INS-1 cells. Unexpectedly, OXM, but not the GLP-1R agonist exendin-4, increased plasma levels of insulin after oral glucose administration. Moreover, OXM administered at doses that potently lower blood glucose had no effect on inhibition of gastric emptying but reduced food intake in WT mice. Taken together, these findings illustrate that although structurally distinct proglucagon-derived peptides such as GLP-1 and OXM engage the GLP-1R, OXM mimics some but not all of the actions of GLP-1R agonists in vivo. These findings may have implications for therapeutic efforts using OXM as a long-acting GLP-1R agonist for the treatment of metabolic disorders.

Effects of gastric emptying on the postprandial ghrelin response

2006 ◽  
Vol 290 (2) ◽  
pp. E389-E395 ◽  
Author(s):  
Wendy A. M. Blom ◽  
Anne Lluch ◽  
Sophie Vinoy ◽  
Annette Stafleu ◽  
Robin van den Berg ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Intravenous Infusion ◽  
Indirect Measurement ◽  
Gastric Emptying Rate ◽  
Total Ghrelin ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Ghrelin Secretion ◽  
Single Blind

Distension and chemosensitization of the stomach are insufficient to induce a ghrelin response, suggesting that postgastric feedback is required. This postgastric feedback may be regulated through insulin. We investigated the relation between gastric emptying rate and the postprandial ghrelin response as well as the role of insulin and other hormones possibly mediating this response. Fifteen healthy men [BMI 21.6 kg/m2 (SD 1.9), age 20.5 yr (SD 2.5)] were studied in a single-blind, crossover design. Subjects received two treatments separated by 1 wk: 1) a dairy breakfast in combination with a 3-h intravenous infusion of glucagon-like peptide-1 (GLP-1), which delays gastric emptying, and 2) a dairy breakfast in combination with a 3-h intravenous infusion of saline. Blood samples were drawn before breakfast and during the infusion. Postprandial ghrelin (total) responses were lower following the saline infusion compared with the GLP-1 infusion ( P < 0.05). Acetaminophen concentrations, an indirect measurement of gastric emptying rate, were inversely correlated with total ghrelin concentrations (saline r = −0.76; 95% CI = −0.90, −0.49, GLP-1 r = −0.47; 95% CI = −0.76, −0.04). Ghrelin concentrations were only weakly correlated with insulin concentrations (saline r = −0.36; 95% CI = −0.69, 0.09; GLP- 1 r = −0.42; 95% CI = −0.73, 0.03), but strongly inversely correlated with GIP concentrations (saline r = −0.74; 95% CI= −0.89, −0.45; GLP-1 r = −0.63; 95% CI = −0.84, −0.27). In conclusion, our results support the hypothesis that ghrelin requires postgastric feedback, which may not be regulated through insulin. Conversely, our data suggest a role of glucose-dependent insulinotropic polypeptide in ghrelin secretion.

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