Gastrin secretion in normal subjects and diabetes patients is inhibited by glucagon-like peptide 1: a role in the gastric side effects of GLP-1-derived drugs?

2019 ◽  
Vol 54 (12) ◽  
pp. 1448-1451 ◽  
Author(s):  
Jens F. Rehfeld ◽  
Filip K. Knop ◽  
Meena Asmar
Keyword(s):  
Side Effects ◽  
Normal Subjects ◽  
Gastrin Secretion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diabetes Patients

scholarly journals Decreased Hypothalamic Glucagon-Like Peptide-1 Receptor Expression in Type 2 Diabetes Patients

2016 ◽  
Vol 101 (5) ◽  
pp. 2122-2129 ◽  
Author(s):  
Jennifer S. ten Kulve ◽  
Liselotte van Bloemendaal ◽  
Rawien Balesar ◽  
Richard G. IJzerman ◽  
Dick F. Swaab ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Receptor Expression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diabetes Patients

Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans

1997 ◽  
Vol 273 (5) ◽  
pp. E981-E988 ◽  
Author(s):  
Michael A. Nauck ◽  
Ulrich Niedereichholz ◽  
Rainer Ettler ◽  
Jens Juul Holst ◽  
Cathrine Ørskov ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Normal Subjects ◽  
Diabetic Patients ◽  
Phenol Red ◽  
Type 2 Diabetic Patients ◽  
Liquid Meal ◽  
Healthy Humans ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulin Responses

Glucagon-like peptide 1 (GLP-1) has been shown to inhibit gastric emptying of liquid meals in type 2 diabetic patients. It was the aim of the present study to compare the action of physiological and pharmacological doses of intravenous GLP-1-(7—36) amide and GLP-1-(7—37) on gastric emptying in normal volunteers. Nine healthy subjects participated (26 ± 3 yr; body mass index 22.9 ± 1.6 kg/m2; hemoglobin A1C 5.0 ± 0.2%) in five experiments on separate occasions after an overnight fast. A nasogastric tube was positioned for the determination of gastric volume by use of a dye-dilution technique (phenol red). GLP-1-(7—36) amide (0.4, 0.8, or 1.2 pmol ⋅ kg−1 ⋅ min−1), GLP-1-(7—37) (1.2 pmol ⋅ kg−1 ⋅ min−1), or placebo was infused intravenously from −30 to 240 min. A liquid meal (50 g sucrose, 8% amino acids, 440 ml, 327 kcal) was administered at 0 min. Glucose, insulin, and C-peptide were measured over 240 min. Gastric emptying was dose dependently slowed by GLP-1-(7—36) amide ( P < 0.0001). Effects of GLP-1-(7—37) at 1.2 pmol ⋅ kg−1 ⋅ min−1were virtually identical. GLP-1 dose dependently stimulated fasting insulin secretion (−30 to 0 min) and slightly reduced glucose concentrations. After the meal (0–240 min), integrated incremental glucose ( P < 0.0001) and insulin responses ( P = 0.01) were reduced (dose dependently) rather than enhanced. In conclusion, 1) GLP-1-(7—36) amide or -(7—37) inhibits gastric emptying also in normal subjects, 2) physiological doses (0.4 pmol ⋅ kg−1 ⋅ min−1) still have a significant effect, 3) despite the known insulinotropic actions of GLP-1-(7—36) amide and -(7—37), the net effect of administering GLP-1 with a meal is no change or a reduction in meal-related insulin responses. These findings suggest a primarily inhibitory function for GLP-1 (ileal brake mechanisms).

scholarly journals Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats

1997 ◽  
Vol 272 (2) ◽  
pp. R726-R730 ◽  
Author(s):  
T. E. Thiele ◽  
G. Van Dijk ◽  
L. A. Campfield ◽  
F. J. Smith ◽  
P. Burn ◽  
...  
Keyword(s):  
Side Effects ◽  
Food Intake ◽  
Consummatory Behavior ◽  
Central Administration ◽  
Short Term ◽  
Nonspecific Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Ob Protein

Leptin (ob protein) and glucagon-like peptide-1-(7-36) amide (GLP-1) are peptides recently proposed to be involved in the regulation of food intake. Although the ability of exogenous leptin and GLP-1 to modulate consummatory behavior is consistent with the suggestion that these peptides are endogenous regulatory agents, central administration of these peptides may have aversive side effects, which could explain the anorexia. In the present experiment, exposure to a saccharine taste was immediately followed by central administration of leptin or GLP-1 to determine if these drugs could produce a conditioned taste aversion (CTA) in rats. At doses equated for producing comparable reductions in short-term food intake, GLP-1, but not leptin, generated a robust CTA. Although leptin caused no aversion, this peptide was the only drug to cause relatively long-term reductions in food consumption (16 h) and body weight (24 h). Hence, the results indicate that central GLP-1 produces aversive side effects, and it is argued that these nonspecific effects may explain the anorectic actions of GLP-1.

scholarly journals Glucagon-Like Peptide-1 Receptor Agonist Treatment Patterns Among Type 2 Diabetes Patients in Six European Countries

2014 ◽  
Vol 5 (2) ◽  
pp. 499-520 ◽  
Author(s):  
Victoria Divino ◽  
Mitch DeKoven ◽  
Shawn Hallinan ◽  
Nebibe Varol ◽  
Sara Bruce Wirta ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Receptor Agonist ◽  
Treatment Patterns ◽  
European Countries ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diabetes Patients

scholarly journals Effects of Glucagon-Like-Peptide-1 Analogue Treatment in Genetic Obesity

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A33-A34
Author(s):  
Mila Sofie Welling ◽  
Cornelis J de Groot ◽  
Lotte Kleinendorst ◽  
Bibian van der Voorn ◽  
Jan Steven Burgerhart ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Weight Loss ◽  
Side Effects ◽  
Metabolic Parameters ◽  
Deletion Syndrome ◽  
Genetic Obesity ◽  
Lifestyle Treatment ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Introduction: Obesity is highly prevalent, comes with serious health burden and is difficult to treat. In a minority, there is a genetic cause for the obesity. In these patients, therapy-resistant obesity is often observed despite intensive lifestyle treatment. Moreover, it is still unclear whether bariatric surgery is less successful in genetic obesity. Liraglutide is a Glucagon-Like-Peptide-1 (GLP-1) receptor agonist or GLP-1 analogue, showing positive effects on metabolic parameters, satiety and weight loss in lifestyle-induced obesity. We present our experiences of GLP-1 analogue treatment in patients with genetic obesity disorders. Methods: Adults with overweight or severe obesity and a molecularly proven genetic cause were treated with liraglutide 3,0 mg daily, in addition to ongoing intensive supportive lifestyle treatment. Anthropometrics, metabolic parameters, resting energy expenditure (REE), side effects, and subjectively reported satiety and quality of life were assessed. Results: Two patients with a heterozygous pathogenic melanocortin 4 recepter variant and two patients with 16p11.2 deletion syndrome, ranging in age between 21 and 32 years and in BMI between 28.1 and 55.7 kg/m2 at baseline, were treated. At end of follow-up, ranging between 33 weeks and 12 years, a mean change in BMI and waist circumference was observed of -5.7 ± 3.8 kg/m2 and -15.2 ± 21.1 cm, respectively. All patients reported better quality of life, three of them also reported improved satiety. Moreover, improvement of metabolic parameters was seen. No clear effect on REE was observed. Two patients experienced mild side effects, e.g. nausea and stomach pain, for a brief period. Conclusion: We here show beneficial effects of GLP-1 analogues on weight, metabolic parameters, and quality of life in four patients with genetic obesity. Satiety improved in three of the four patients. All patient achieved at least the clinically relevant 5–10% weight loss. Our findings suggest that GLP-1 analogue treatment might be an effective treatment option, in addition to a healthy lifestyle, for patients with genetic obesity.

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