Glucagon-like peptide 1 (GLP-1) suppresses ghrelin levels in humans via increased insulin secretion.
ABSTRACT Ghrelin is an orexigenic peptide predominantly secreted by the stomach. Ghrelin plasma levels rise before meal ingestion and sharply decline afterwards, but the mechanisms controlling ghrelin secretion are largely unknown. Since meal ingestion also elicits the secretion of the incretin hormone glucagon-like peptide 1 (GLP-1), we examined whether exogenous GLP-1 administration reduces ghrelin secretion in humans.
14 healthy male volunteers were given intravenous infusions of GLP-1(1.2 pmol x kg(-1) min(-1)) or placebo over 390 min. After 30 min, a solid test meal was served. Venous blood was drawn frequently for the determination of glucose, insulin, C-peptide, GLP-1 and ghrelin.
During the infusion of exogenous GLP-1 and placebo, GLP-1 plasma concentrations reached steady-state levels of 139+/-15 pmol/l and 12+/-2 pmol/l, respectively (p<0.0001). During placebo infusion, ghrelin levels were significantly reduced in the immediate postprandial period (p<0.001), and rose again afterwards. GLP-1 administration prevented the initial postprandial decline in ghrelin levels, possibly as a result of delayed gastric emptying, and significantly reduced ghrelin levels 150 and 360 min after meal ingestion (p<0.05). The patterns of ghrelin concentrations in the experiments with GLP-1 and placebo administration were inversely related to the respective plasma levels of insulin and C-peptide.
GLP-1 reduces the rise in ghrelin levels in the late postprandial period at supraphysiological plasma levels. Most likely, these effects are indirectly mediated through its insulinotropic action. The GLP-1-induced suppression of ghrelin secretion might be involved in its anorexic effects.
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ABSTRACT: Roux-en-Y gastric bypass (RYGB) surgery reverses diabetes (T2DM) in ~80% of patients. Ghrelin regulates glucose homeostasis, but its role in T2DM remission after RYGB surgery is unclear. Nine obese T2DM subjects underwent a mixed meal tolerance test before and at 1 and 12 months after RYGB. Changes in ghrelin, body weight, GLP-1, glucose tolerance, and insulin sensitivity were measured. At 1 month, body weight, glycemia and insulin sensitivity were improved, while ghrelin concentrations were reduced (p<0.05). After 12 months, body weight and fasting glucose were reduced (30% and 16% respectively; p<0.05) and insulin sensitivity was enhanced (3-fold; p<0.05). Ghrelin suppression improved by 32% at 12 months (p<0.05), and this was associated with weight loss (R = 0.72, p=0.03), enhanced insulin sensitivity (R = -0.78, p=0.01) and peak post-prandial GLP-1 (R = -0.73, p=0.03). These data suggest that post-prandial ghrelin suppression may be part of the mechanism that contributes to diabetes remission after RYGB surgery.Diabetes Obesity and Metabolism 05/2013; · 5.18 Impact Factor
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ABSTRACT: BACKGROUND: To explore the effects of acute administration of GLP-1 and GIP on circulating levels of key adipocyte-derived hormones and gut-brain peptides with established roles in energy and appetite regulation, modulation of insulin sensitivity and inflammation. METHODS: Six obese male patients with diet-treated type 2 diabetes (T2DM) and 6 healthy lean subjects were studied. The protocol included 4 experiments for each participant that were carried out in randomised order and comprised: GLP-1 infusion at a rate of 1pmol/kg/min for 4h, GIP at a rate of 2pmol/kg/min, GLP-1+GIP and placebo infusion. Plasma leptin, adiponectin, IL-6, insulin, ghrelin and obestatin were measured at baseline, 15, 60, 120, 180 and 240min following the start of infusion. RESULTS: Patients with T2DM had higher baseline IL-6 compared with healthy [day of placebo infusion: T2DM IL-6 mean (SEM) 1.3 (0.3)pg/ml vs 0.3 (0.1)pg/ml, p=0.003]. GLP-1 infusion in T2DM was associated with a significant reduction in circulating IL-6 [baseline IL-6 1.2pg/ml vs IL-6=0.7 at 120min, p=0.0001; vs IL-6=0.8 at 180min, p=0.001]. There was no significant change in leptin, adiponectin, ghrelin or obestatin compared to baseline on all 4 experimental days in both groups. CONCLUSION: Short-term infusion of supraphysiological concentrations of GLP-1 in T2DM results in suppression of IL-6, a key inflammatory mediator strongly linked to development of obesity and T2DM-related insulin resistance. It remains to be confirmed whether GLP-1-based diabetes therapies can impact favourably on cardiovascular outcomes.Regulatory Peptides 03/2013; · 2.06 Impact Factor
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ABSTRACT: Glucagon-like peptide-1 (GLP-1), an insulinotropic gastrointestinal peptide that is primarily produced by intestinal endocrine L-cells, stimulates satiety. Ghrelin, a hormone that is produced predominantly by the stomach stimulates hunger. There are two forms of ghrelin: active ghrelin and inactive des-acyl ghrelin. After depriving mice of food for 24 h, we demonstrated that the systemic administration of liraglutide (100 μ g/kg), a human GLP-1 analog that binds to the GLP-1 receptor, increased (1.4-fold) the plasma levels of active GLP-1 and suppressed the plasma levels of active and des-acyl ghrelin after 1 h. Despite the elevated plasma levels of active GLP-1 (11-fold), liraglutide had no effect on the plasma levels of active or des-acyl ghrelin after 12 h. These findings demonstrated that liraglutide suppresses the plasma levels of active and des-acyl ghrelin independently of active GLP-1 levels in fasted mice, suggesting a novel in vivo biological effect of liraglutide beyond regulating plasma GLP-1.ISRN endocrinology. 01/2013; 2013:184753.