Gastric emptying and release of incretin hormones after glucose ingestion in humans.

This study investigated in eight healthy male volunteers (a) the gastric emptying pattern of 50 and 100 grams of glucose; (b) its relation to the phase of interdigestive motility (phase I or II) existing when glucose was ingested; and (c) the interplay between gastric emptying or duodenal perfusion of glucose (1.1 and 2.2 kcal/min; identical total glucose loads as orally given) and release of glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1(7-36)amide (GLP-1), C-peptide, insulin, and plasma glucose. The phase of interdigestive motility existing at the time of glucose ingestion did not affect gastric emptying or any metabolic parameter. Gastric emptying of glucose displayed a power exponential pattern with a short initial lag period. Duodenal delivery of glucose was not constant but exponentially declined over time. Increasing the glucose load reduced the rate of gastric emptying by 27.5% (P < 0.05) but increased the fractional duodenal delivery of glucose. Both glucose loads induced a fed motor pattern which was terminated by an antral phase III when approximately 95% of the meal had emptied. Plasma GLP-1 rose from basal levels of approximately 1 pmol/liter of peaks of 3.2 +/- 0.6 pmol/liter with 50 grams of glucose and of 7.2 +/- 1.6 pmol/liter with 100 grams of glucose. These peaks occurred 20 min after glucose intake irrespective of the load. A duodenal delivery of glucose exceeding 1.4 kcal/min was required to maintain GLP-1 release in contrast to ongoing GIP release with negligibly low emptying of glucose. Oral administration of glucose yielded higher GLP-1 and insulin releases but an equal GIP release compared with the isocaloric duodenal perfusion. We conclude that (a) gastric emptying of glucose displays a power exponential pattern with duodenal delivery exponentially declining over time and (b) a threshold rate of gastric emptying of glucose must be exceeded to release GLP-1, whereas GIP release is not controlled by gastric emptying.

[1]  C. Beglinger,et al.  Intestinal phase of human antro‐pyloro‐duodenal motility: cholinergic and CCK‐mediated regulation , 1996, European journal of clinical investigation.

[2]  B. Göke,et al.  Regulation of glucagon-like peptide-1 secretion from rat ileum by neurotransmitters and peptides. , 1995, The Journal of endocrinology.

[3]  B. Göke,et al.  Cell and molecular biology of the incretin hormones glucagon-like peptide-I and glucose-dependent insulin releasing polypeptide. , 1995, Endocrine reviews.

[4]  B. Göke,et al.  Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. , 1995, Digestion.

[5]  J. Chayvialle,et al.  Regulation of glucagon-like peptide-1-(7-36) amide secretion by intestinal neurotransmitters and hormones in the isolated vascularly perfused rat colon. , 1994, Endocrinology.

[6]  S. Kahn,et al.  Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. , 1994, The Journal of clinical investigation.

[7]  P. Brubaker,et al.  Regulation of intestinal proglucagon-derived peptide secretion by glucose-dependent insulinotropic peptide in a novel enteroendocrine loop. , 1993, Endocrinology.

[8]  N. Vidon,et al.  Effect of ethanol on absorption of a nutrient solution in the upper human intestine. , 1993, Scandinavian journal of gastroenterology.

[9]  J. Holst,et al.  Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. , 1993, The Journal of clinical investigation.

[10]  C. Beglinger,et al.  Cephalic stimulation of gastrointestinal secretory and motor responses in humans. , 1992, Gastroenterology.

[11]  J. Holst,et al.  Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus. , 1992, The New England journal of medicine.

[12]  M. Anvari,et al.  Relation of pyloric motility to pyloric opening and closure in healthy subjects. , 1992, Gut.

[13]  H. Vermeer,et al.  Glucagon‐like peptide‐1 cells in the gastrointestinal tract and pancreas of rat, pig and man , 1992, European journal of clinical investigation.

[14]  C. Beglinger,et al.  Role of cholecystokinin in the regulation of gastric emptying and pancreatic enzyme secretion in humans. Studies with the cholecystokinin-receptor antagonist loxiglumide. , 1991, Gastroenterology.

[15]  S. Werlin,et al.  EFFECTS OF CHOLECYSTOKININ RECEPTOR BLOCKADE ON PANCREATIC AND BILIARY FUNCTION IN HEALTHY VOLUNTEERS , 1991, Gastroenterology.

[16]  P. Brubaker.  Regulation of intestinal proglucagon-derived peptide secretion by intestinal regulatory peptides. , 1991, Endocrinology.

[17]  C. Beglinger,et al.  Effect of a cholecystokinin antagonist on meal-stimulated insulin and pancreatic polypeptide release in humans. , 1991, The Journal of clinical endocrinology and metabolism.

[18]  J. Dent,et al.  Hyperglycaemia stimulates pyloric motility in normal subjects. , 1991, Gut.

[19]  M. Horowitz,et al.  The effect of short-term dietary supplementation with glucose on gastric emptying in humans , 1991, British Journal of Nutrition.

[20]  G L Amidon,et al.  The influence of the interdigestive migrating myoelectric complex on the gastric emptying of liquids. , 1990, Gastroenterology.

[21]  J. Elashoff,et al.  Pancreatobiliary responses to an intragastric amino acid meal: comparison to albumin, dextrose, and a maximal cholecystokinin stimulus. , 1989, Gastroenterology.

[22]  J. Dent,et al.  Pyloric motor response to intraduodenal dextrose involves muscarinic mechanisms. , 1989, Gastroenterology.

[23]  J. Meyer,et al.  Inhibition of gastric emptying by glucose depends on length of intestine exposed to nutrient. , 1989, The American journal of physiology.

[24]  J. Dent,et al.  Stimulation of pyloric motility by intraduodenal dextrose in normal subjects. , 1988, Gut.

[25]  J. Dent,et al.  Extrinsic and intrinsic neural control of pyloric sphincter pressure in the dog. , 1988, The Journal of physiology.

[26]  J. Dent,et al.  Relationship of the motor activity of the antrum, pylorus, and duodenum to gastric emptying of a solid-liquid mixed meal. , 1988, Gastroenterology.

[27]  J. Barnett,et al.  Serum glucose concentration as a modulator of interdigestive gastric motility. , 1988, Gastroenterology.

[28]  B. Krevsky,et al.  Biphasic nature of gastric emptying. , 1988, Gut.

[29]  S. Bloom,et al.  GLUCAGON-LIKE PEPTIDE-1 7-36: A PHYSIOLOGICAL INCRETIN IN MAN , 1987, The Lancet.

[30]  S. Saafan.  GASTRIC EMPTYING AS A DETERMINANT OF THE ORAL GLUCOSE TOLERANCE TEST , 1987 .

[31]  J. N. Hunt,et al.  Effect of meal volume and energy density on the gastric emptying of carbohydrates. , 1985, Gastroenterology.

[32]  H. Smith,et al.  Gastric emptying of solid radiopaque markers: studies in healthy subjects and diabetic patients. , 1984, Gastroenterology.

[33]  R. Smallwood,et al.  Human antroduodenal motility, pyloric closure, and domperidone. , 1984, Scandinavian journal of gastroenterology. Supplement.

[34]  P. McHugh,et al.  Regulation of the gastric emptying of glucose. , 1983, Gastroenterology.

[35]  J. Elashoff,et al.  Analysis of gastric emptying data. , 1982, Gastroenterology.

[36]  W. Creutzfeldt,et al.  Decreased GIP Secretion through Impairment of Absorption1 , 1980 .

[37]  J. Elashoff,et al.  How gastric emptying of carbohydrate affects glucose tolerance and symptoms after truncal vagotomy with pyloroplasty. , 1980, Gastroenterology.

[38]  N. Mei.  Vagal glucoreceptors in the small intestine of the cat. , 1978, The Journal of physiology.

[39]  J. Malagelada,et al.  Measurement of gastric functions during digestion of ordinary solid meals in man. , 1976, Gastroenterology.

[40]  J. Meyer,et al.  The effect of acute hyperglycemia on gastric emptying in man. , 1976, Gastroenterology.

[41]  J. Brown,et al.  Stimulation of insulin secretion by gastric inhibitory polypeptide in man. , 1973, The Journal of clinical endocrinology and metabolism.

[42]  M. Hobsley,et al.  Use of an inert marker (phenol red) to improve accuracy in gastric secretion studies , 1969, Gut.

[43]  M. Hobsley,et al.  Useofaninert marker (phenol red) toimprove accuracyingastric secretion studies , 1969 .

[44]  G. F. Fisher,et al.  Reproducibility of the Oral Glucose Tolerance Test , 1965, Diabetes.

[45]  S. Hyden.  A turbidimetric method for the determination of higher polyethylene glycols in biological materials. , 1956 .

[46]  J. N. Hunt,et al.  The pattern of emptying of the human stomach * , 1951, The Journal of physiology.