GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans

Abstract

The aim of the present study was to assess the effect of glucagon-like peptide-1 (GLP-1) on solid gastric emptying and the subsequent release of pancreatic and intestinal hormones. In eight men [age 33.6 ± 2.5 yr, body mass index 24.1 ± 0.9 (means ± SE)], scintigraphic solid gastric emptying during infusion of GLP-1 (0.75 pmol ⋅ kg−1 ⋅ min−1) or saline was studied for 180 min. Concomitantly, plasma concentrations of C- and N-terminal GLP-1, glucose, insulin, C-peptide, glucagon, and peptide YY (PYY) were assessed. Infusion of GLP-1 resulted in a profound inhibition of both the lag phase (GLP-1: 91.5, range 73.3–103.6 min vs. saline: 19.5, range 10.2–43.4 min) and emptying rate (GLP-1: 0.34, range 0.06–0.56 %/min vs. saline: 0.84, range 0.54–1.33 %/min; P< 0.01 for both) of solid gastric emptying. Concentrations of both intact and total GLP-1 were elevated to supraphysiological levels. Plasma glucose and glucagon concentrations were below baseline during infusion of GLP-1 in contrast to saline infusion, where concentrations were elevated above baseline (both P< 0.001). The insulin and C-peptide responses were lower during infusion with GLP-1 than with saline ( P < 0.004 and P < 0.001, respectively). Plasma PYY concentrations decreased below baseline during GLP-1 infusion in contrast to saline, where concentrations were elevated above baseline ( P = 0.04). Infusion of GLP-1 inhibits solid gastric emptying with secondary effects on the release of insulin, C-peptide, and glucagon, resulting in lower plasma glucose concentrations. In addition, the release of PYY into the circulation is inhibited by GLP-1 infusion, suggesting a negative feedback of GLP-1 on the function of the L-cell.

No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects

“…If so, what would be the mechanism of action? GLP-1 is considered an ileal brake hormone, [31][32][33] and a possible mechanism of action is a paracrine mechanism where GLP-1 secreted from the L-cells in the intestinal epithelium enters the lamina propria and interacts with nerve endings of sensory afferent neurons. If GLP-2 works as a paracrine transmitter as does GLP-1, the question is what GLP-2 plasma concentration is needed to gain GLP-2 concentrations in the lamina propria sufficient to activate the afferent neurons.…”

Glucagon-Like Peptide-1 Synthetic Analogs: New Therapeutic Agents for Use in the Treatment of Diabetes Mellitus

“…It is important to note that GLP-1 is also an inhibitor of gastrointestinal secretion and motility, not only in healthy individuals [38], but in type 2 diabetic subjects as well [21,31,39]. GLP-1 slows gastric emptying and delays nutrient absorption, actions that are likely to play a major role in determining the effectiveness of GLP-1 as a regulator of blood glucose concentration during the time immediately following ingestion of a meal [40].…”

Genetic variation inGlp1rexpression influences the rate of gastric emptying in mice

“…The mechanism by which GLP-1 inhibits gastric emptying is thought to involve receptors located either in the central nervous system or associated with afferent pathways to the brain stem (9,21,60). In addition to the deceleration of gastric emptying, GLP-1 is involved in regulating satiety, as shown in normal-weight and obese men infused with 33,34). GLP-1 also decreases food intake; by contrast, central administration of the GLP-1 receptor (GLP-1R) antagonist exendin-(9-39) stimulates food intake (14, 54).…”