Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men.

Abstract

BACKGROUND: Peripheral administration of glucagon-like peptide-1 (GLP-1) for four hours, to normal weight and obese humans, decreases food intake and suppresses appetite. OBJECTIVE: The aim of this study was to assess the effect of an eight hour infusion of GLP-1 on appetite and energy intake at lunch and dinner in obese subjects. DESIGN: Randomised, blinded cross-over design with intravenous infusion of GLP-1 (0.75 pmol Á kg 71 Á min 71 ) or saline. SUBJECTS: Eight obese (body mass index, BMI, 45.5 AE 2.3 kgam 2 ) male subjects. MEASUREMENTS: Ad libitum energy intake at lunch (12.00 h) and dinner (16.00 h) after an energy ®xed breakfast (2.4 MJ) at 08.00 h. Appetite sensations using visual analogue scales, (VAS) immediately before and after meals and hourly in-between. Blood samples for the analysis of glucose, insulin, C-peptide, GLP-1 and peptide YY. Gastric emptying after breakfast and lunch using a paracetamol absorption technique. RESULTS: Hunger ratings were signi®cantly lower with GLP-1 infusion. The summed ad libitum energy intake at lunch and dinner was reduced by 1.7 AE 0.5 MJ (21 AE 6%) by GLP-1 infusion (P 0.01). Gastric emptying was delayed by GLP-1 infusion, and plasma glucose concentrations decreased (baseline: 6.6 AE 0.35 mmolaL; nadir: 5.3 AE 0.15 mmolaL). No nausea was recorded during GLP-1 infusion. CONCLUSIONS: Our results demonstrate that GLP-1 decreases feelings of hunger and reduces energy intake in obese humans. One possible mechanism for this ®nding might be an increased satiety primarily mediated by gastric vagal afferent signals.

Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes

“…Although differences in study design preclude the direct comparison of our results with those obtained with other peptide hormones, it is noteworthy that the magnitude of the reduction in food intake observed in response to pramlintide is similar to that reported for other gastrointestinal satiety signals, such as GLP-1 [9][10][11], PYY [13,14] and CCK [1-5, 7, 8]. In most of the aforementioned studies, peptides were administered via continuous i.v.…”

“…Whether a given peptide hormone has a physiological role in the regulation of food intake and body weight is typically established by supporting evidence from animal studies (using gain-offunction studies with the peptide itself and loss-of-function studies with selective antagonists and/or gene knock-outs) and from clinical studies assessing the effect of the peptide on satiety and food intake in humans [1][2][3][4][5]. To date, randomised, controlled crossover studies in humans have reported an increase in food intake at a buffet meal following the administration of the gastric hormone ghrelin [6], and a decrease following the administration of the gut hormones cholecystokinin (CCK) [7,8], glucagon-like peptide-1 (GLP-1) [9][10][11], oxyntomodulin [12] and peptide YY3-36 [13,14], and the islet hormones glucagon [15], pancreatic polypeptide [16] and somatostatin [17].…”

Incretins, insulin secretion and Type 2 diabetes mellitus

“…This effect is also desirable in patients with diabetes, because the slower gastric emptying rate reduces postprandial glucose excursions as is evident from the use of another potent gastric inhibitor, amylin, for diabetes treatment [98]; finally, GLP-1 inhibits appetite and food intake. This has been shown in both normal subjects, obese subjects and subjects with Type 2 diabetes mellitus [99,100,101]. The latter effect would support attempts at weight reduction in patients with Type 2 diabetes and, if effective, would be considered most desirable.…”

Lower glucose-dependent insulinotropic polypeptide (GIP) response but similar glucagon-like peptide 1 (GLP-1), glycaemic, and insulinaemic response to ancient wheat compared to modern wheat depends on processing

“…Lower GIP response S Bakh j et al the GIP response compared to the GLP-1 response in the present study. GIP is synthesized and released from the duodenum and proximal jejunum, whereas GLP-1 is primarily synthesized and released from the ileum (Hoist, 1997;Näslund et al, 1999). It is therefore likely that a larger portion of bread per test meal would lead to more pronounced differences in the GLP-1 responses.…”