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

Abstract

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 Ͻ 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 ‫ف‬ 95% of the meal had emptied. Plasma GLP-1 rose from basal levels of ‫ف‬ 1 pmol/liter to peaks of 3.2 Ϯ 0.6 pmol/liter with 50 grams of glucose and of 7.2 Ϯ 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 con-

Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients

“…Acute stimulation tests such as IVGTT or mixed-meal tolerance tests (MMTT) measure only hormonal release from the beta cell subpopulation that can be rapidly activated and some (e.g. MMTT) are influenced by gastrointestinal variables [22]. In contrast, prolonged glycaemic stimulation during glucose clamp tests is believed to recruit virtually all beta cells in a glucose-responsive state [23].…”

Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice

“…Glucose-dependent insulinotropic polypeptide (GIP) is an important gastro-intestinal hormone synthesized and secreted into the blood stream by the duodenal endocrine K cells after ingestion of a mixed meal [3][4][5]. To induce a biological response, it binds to glucosedependent insulinotropic polypeptide receptors (GIPRs), expressed in the endocrine pancreas, gastrointestinal tract, brain, immune and cardiovascular systems, testis, pituitary, lung, kidney, thyroid, several regions in the central nervous system and adipose tissue [6].…”

Reducing dietary fat from a meal increases the bioavailability of exogenous carbohydrate without altering plasma glucose concentration

“…However, many of the mechanisms governing gastrointestinal peptide secretion remain unclear. Fat content in the diet has been found to be a trigger for the secretion of these gastrointestinal peptides (14,32,36), but the impact of removing fat calories from the diet on the magnitude of change in the secretion of these peptides is not known.The primary goal of this study was to determine the acute glycemic and endocrine responses to the reduction of fat content from a meal. To better address the influence of ingested fat on postprandial glucose response, subjects ingested tracerlabeled carbohydrate ([ 13 C]glucose) to measure the delivery of the exogenous glucose to the systemic circulation.…”

“…Over the past several years, the gastrointestinal tract has been found to release important peptide hormones into the systemic circulation in response to the contents of the meal (1,14,21). These gastrointestinal peptides, such as glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY ) have several important metabolic actions, including mediating pancreatic insulin secretion and effecting the sensation of hunger and satiety (3,27,36). However, many of the mechanisms governing gastrointestinal peptide secretion remain unclear.…”

“…However, many of the mechanisms governing gastrointestinal peptide secretion remain unclear. Fat content in the diet has been found to be a trigger for the secretion of these gastrointestinal peptides (14,32,36), but the impact of removing fat calories from the diet on the magnitude of change in the secretion of these peptides is not known.…”