Glucagon-like peptide-1 inhibits gastric emptying  via vagal afferent-mediated central mechanisms

Exogenous administration of glucagon-like peptide-1-(7—36) amide (GLP-1), an insulinotropic hormone, inhibits gastric emptying and acid secretion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and peripheral administration of the GLP-1 receptor antagonist exendin(9—39) amide enhanced emptying of a glucose meal, whereas intracerebroventricular exendin was ineffective. The rate of saline emptying was attenuated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibition by GLP-1. Vagal afferent denervation abolished the central and peripheral action of GLP-1 on gastric emptying. Neither peripheral cholinergic nor adrenergic blockade altered the delay of methyl cellulose meal emptying by intracisternal GLP-1 injection. Acid secretion in conscious pylorus-ligated rats was inhibited by intracisternal GLP-1 administration, whereas systemic GLP-1 was ineffective. These results support the notion that GLP-1 receptors participate in the central and peripheral regulation of gastric function. Furthermore, vagal afferent nerves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiological modulator of gastric function.

Download Full-text

Targeted disruption of the murine CCK1 receptor gene reduces intestinal lipid-induced feedback inhibition of gastric function

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00569.2005 ◽

2006 ◽

Vol 291 (1) ◽

pp. G156-G162 ◽

Cited By ~ 42

Author(s):

K. L. Whited ◽

D. Thao ◽

K. C. Kent Lloyd ◽

A. S. Kopin ◽

H. E. Raybould

Keyword(s):

Gastric Emptying ◽

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Feedback Inhibition ◽

Vagal Afferents ◽

Afferent Pathway ◽

Gastric Function ◽

Vagal Afferent ◽

Fos Expression

Cholecystokinin (CCK), acting at CCK1 receptors (CCK1Rs) on intestinal vagal afferent terminals, has been implicated in the control of gastrointestinal function and food intake. Using CCK1R−/− mice, we tested the hypothesis that lipid-induced activation of the vagal afferent pathway and intestinal feedback of gastric function is CCK1R dependent. In anesthetized CCK1R+/+ (“wild type”) mice, meal-stimulated gastric acid secretion was inhibited by intestinal lipid infusion; this was abolished in CCK1R−/− mice. Gastric emptying of whole egg, measured by nuclear scintigraphy in awake mice, was significantly faster in CCK1R−/− than CCK1R+/+ mice. Gastric emptying of chow was significantly slowed in response to administration of CCK-8 (22 pmol) in CCK1R+/+ but not CCK1R−/− mice. Activation of the vagal afferent pathway was measured by immunohistochemical localization of Fos protein in the nucleus of the solitary tract (NTS; a region where vagal afferents terminate). CCK-8 (22 pmol ip) increased neuronal Fos expression in the NTS of fasted CCK1R+/+ mice; CCK-induced Fos expression was reduced by 97% in CCK1R−/− compared with CCK1R+/+ mice. Intralipid (0.2 ml of 20% Intralipid and 0.04 g lipid), but not saline, gavage increased Fos expression in the NTS of fasted CCK1R+/+ mice; lipid-induced Fos expression was decreased by 47% in CCK1R−/− compared with CCK1R+/+mice. We conclude that intestinal lipid activates the vagal afferent pathway, decreases gastric acid secretion, and delays gastric emptying via a CCK1R-dependent mechanism. Thus, despite a relatively normal phenotype, intestinal feedback in response to lipid is severely impaired in these mice.

Download Full-text

Effects of exogenous glucagon-like peptide-1 on gastric emptying and glucose absorption in the critically ill: Relationship to glycemia*

Critical Care Medicine ◽

10.1097/ccm.0b013e3181d9d87a ◽

2010 ◽

Vol 38 (5) ◽

pp. 1261-1269 ◽

Cited By ~ 59

Author(s):

Adam M. Deane ◽

Marianne J. Chapman ◽

Robert J. L. Fraser ◽

Matthew J. Summers ◽

Antony V. Zaknic ◽

...

Keyword(s):

Gastric Emptying ◽

Critically Ill ◽

Glucose Absorption ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Download Full-text

Effects of a D-Xylose Preload With or Without Sitagliptin on Gastric Emptying, Glucagon-Like Peptide-1, and Postprandial Glycemia in Type 2 Diabetes

Diabetes Care ◽

10.2337/dc12-2294 ◽

2013 ◽

Vol 36 (7) ◽

pp. 1913-1918 ◽

Cited By ~ 35

Author(s):

T. Wu ◽

M. J. Bound ◽

B. R. Zhao ◽

S. D. Standfield ◽

M. Bellon ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gastric Emptying ◽

Postprandial Glycemia ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Download Full-text

Effect of Chronic Central Administration of Glucagon-Like Peptide-1 (7-36) Amide on Food Consumption and Body Weight in Normal and Obese Rats

Obesity Research ◽

10.1002/j.1550-8528.1998.tb00329.x ◽

1998 ◽

Vol 6 (2) ◽

pp. 147-156 ◽

Cited By ~ 43

Author(s):

Harry R. Davis ◽

Deborra E. Mullins ◽

Jesse M. Pines ◽

Lizbeth M. Hoos ◽

Constance F. France ◽

...

Keyword(s):

Body Weight ◽

Food Consumption ◽

Central Administration ◽

Obese Rats ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Download Full-text

Effect of Two Types of β-Adrenergic Blockade on Gastric Acid Secretion During Pentagastrin Stimulation in Non-vagotomized and in Vagotomized Gastric Fistula Dogs

Scandinavian Journal of Gastroenterology ◽

10.3109/00365527909181416 ◽

1979 ◽

Vol 14 (7) ◽

pp. 857-864 ◽

Cited By ~ 11

Author(s):

F. Gottrup ◽

J. Ørnsholt ◽

D. Andersen

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Gastric Fistula ◽

Adrenergic Blockade

Download Full-text

Glucagon-like peptide-1 and insulin synergistically activate vagal afferent neurons

Neuropeptides ◽

10.1016/j.npep.2017.05.003 ◽

2017 ◽

Vol 65 ◽

pp. 77-82 ◽

Cited By ~ 12

Author(s):

Yusaku Iwasaki ◽

Chayon Goswami ◽

Toshihiko Yada

Keyword(s):

Afferent Neurons ◽

Vagal Afferent ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Download Full-text

Effects of bombesin on food intake and gastric acid secretion in cats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.1.r181 ◽

1989 ◽

Vol 256 (1) ◽

pp. R181-R186

Author(s):

A. Bado ◽

M. J. Lewin ◽

M. Dubrasquet

Keyword(s):

Gastric Emptying ◽

Food Intake ◽

Gastric Secretion ◽

Acid Secretion ◽

Gastric Fistula ◽

Single Class ◽

Heidenhain Pouch ◽

Daily Food Intake ◽

Feeding Experiments ◽

Daily Food

The brain and gut peptide bombesin has been reported both to stimulate gastric secretion and to induce satiety. To understand how the peripheral administration of bombesin affects food intake and whether gastric mechanisms are involved, a comparative study of the doses of bombesin active on gastric secretion, gastric emptying, and food intake was undertaken in cats provided with a gastric fistula and a denervated Heidenhain pouch. The smallest dose of intravenous bombesin that stimulated significantly basal acid secretion (20 pmol.kg-1.h-1) by the gastric fistula also enhanced meal-stimulated acid secretion by the Heidenhain pouch (+138%, P less than 0.01), delayed gastric emptying of a liquid protein meal (-30%, P less than 0.01), and suppressed food intake when the test meal was allowed to reach the stomach (-15%, P less than 0.01). Conversely, in sham-feeding experiments, the same dose of bombesin increased food intake (+35%, P less than 0.01). In full-day experiments conducted in nonfasted cats, bombesin decreased both the food intake in the 4-h period after the infusion and the daily food intake, whereas octapeptide cholecystokinin induced a transient satiety but did not decrease daily food intake. These results indicate that in cats the interaction of bombesin with "pregastric" mechanisms is not sufficient to induce satiety and that a relation could exist between the effects of bombesin on gastric secretion, emptying, and food intake. A single class of receptors might be involved in these peripheral effects of bombesin.

Download Full-text