Gastrin AND Incretin

The discoverers of secretin already thought of the existence of a chemical excitant for the internal secretion of the pancreas. Numerous experiments have been performed and published between 1906 and 1935 testing the effect of injected or ingested duodenal ("secretin") extracts on fasting or elevated blood glucose levels of normal or diabetic animals and humans with contradictory results. In 1940, after a series of negative dog experiments performed by an opinion leader, the existence of an incretin was considered questionable and further research stopped for more than 20 years...

Pituitary adenylate cyclase-activating polypeptide (PACAP) is localized to pancreatic ganglia governing the parasympathetic nerves, which contribute to prandial insulin secretion. We hypothesized that this contribution involves PACAP and show here that the PACAP receptor antagonist PACAP-(6---27) (1.5 nmol/kg iv) reduces the 15-min insulin response to gastric glucose (150 mg/mouse) by 18% in anesthetized mice (P = 0.041). The reduced insulinemia was not due to inhibited release of the incretin factor glucagon-like peptide 1 (GLP-1) because PACAP-(6---27) enhanced the GLP-1 response to gastric glucose...

The stimulus-secretion coupling of the insulin-producing pancreatic islet beta cell is subject to functional maturation during fetal life. We studied the maturation of a glucose-responsive insulin release from fetal rat islets and specifically investigated the impact of peptidergic regulation. To this end, islets were isolated from 21-day-old fetal rats and maintained for 7 days in tissue culture at 3.3 or 11.1 mM glucose and various supplements. In islets cultured in low glucose, acutely raising the ambient glucose concentration to 16...

Glucagon-like peptide-1 (GLP-1) may be one of the enterogastrone hormones of the ileal brake mechanism. We therefore studied its effects on gastric lipase secretion in healthy volunteers and vagotomized patients during infusion of pentagastrin. The intestinal incretin hormone GLP-1 (glucagon-like peptide-1, 7-36 amide) was investigated because of its inhibitory effects on gastric acid secretion and motility. GLP-1 infused intravenously in amounts corresponding to the postprandial release significantly inhibited pentagastrin-stimulated gastric lipase secretion and lipolytic activity...

Intraduodenal fat inhibits gastric acid secretion via the release of one or more hormonal enterogastrones thought to arise from ileocolonic mucosa. This study determined whether glucagon-like peptide-1 (GLP-1)-(7-36) amide and peptide YY (PYY), colocalized in L cells found in the ileum, mediate intraduodenal fat-induced inhibition of stimulated gastric acid, and evaluated the influence of cholecystokinin-A (CCK-A) receptor activation. Gastric acid secretion in response to duodenal perfusions of 8% peptone was measured in conscious dogs with gastric and duodenal cannulas...

Intravenous infusions of glucagon-like peptide-1(7-36) amide (GLP-1; 35 pmol min-1 kg-1 for 10 min) produced a significant rise in mean heart rate, without significant change in mean aortic blood pressure, together with a significant rise in mean arterial plasma insulin, but not in plasma pancreatic glucagon or pancreatic polypeptide concentration, in conscious calves given exogenous glucose (30-60 micromol min-1 kg-1 i.v.). The insulinotropic effect was eliminated in the presence of exogenous amino acids (0...

Progress in gut hormone research has considerably increased our knowledge in gastrointestinal physiology. However, this knowledge has not yet helped the understanding of common gastrointestinal diseases. A pathophysiological role of gut hormones has been established only for rare conditions This is because the clinical significance of the gut hormones is difficult to evaluate. Morphological and biochemical methods used in classical endocrinology can rarely be applied to gastrointestinal endocrinology because of the special design of the gut hormone system...

In pregnancy the secretion of a number of gastro-enteropancreatic hormones is considerably altered. These changes might be involved in the gestational modification of gastrointestinal physiology. The enteral stimulation of insulin secretion (the incretin effect) is diminished in pregnancy--both when determined indirectly and when the gastric inhibitory polypeptide (GIP) response to glucose ingestion is considered. Whether this is important for the deterioration of glucose tolerance in pregnancy is uncertain...

Ingestion of food stimulates secretion of bile and release of gut hormones that enhance nutrient-stimulated release of insulin. The extent of physiologic participation of bile in the enteroinsular axis was examined in seven conscious dogs (weight: 20 +/- 2 kg) that were prepared for study with chronic cannulas placed in the duodenum opposite the ampulla of Vater. On separate days, a meal consisting of 10 gm (MG-10), 25 gm (MG-25), or 62 gm (MG-62) of glucose (dextrose) was given orally in the presence of normal bile flow or during bile diversion...

A greater plasma concentration of insulin after isoglycemic enteral than after parenteral administration of glucose is called the incretin effect. The primary mediator of this effect, gastric inhibitory polypeptide, may not account for the complete manifestation of this phenomenon. We evaluated other gastroenteric polypeptides with respect to a differential response to oral ingestion of glucose and intravenous administration of glucose at rates that achieved arterial plasma glucose concentrations matched to those from orally administered glucose...

The influence of oral trypsin inhibitor (TI) or vehicle (V) during 4 weeks on oral glucose tolerance (OGT) and on the enteroinsular axis (EIA) of insulin, CCK, and gastrin was studied in five beagles. TI improved OGT throughout the 180-min test period. Incremental areas of insulin and gastrin did not differ from 0 to 60 min after TI and V treatment, but both increased significantly from 60 to 180 min after TI. From 0 to 60 min CCK decreased significantly in the TI group, whereas the differences (delta) in hormone changes (insulin, CCK, gastrin) observed during oral and intravenous glucose showed a decrease for their incremental areas during this period...

The insulin response to oral and intravenous glucose was measured in ten patients after resection of antrum, duodenum, proximal jejunum, and the head of pancreas (Whipple's operation). Compared to matched normal subjects the operation reduced neither the total nor the gut hormone induced part of the insulin response to oral glucose. The results suggest, that hormones from the first part of the intestinal tract are not necessary as incretins.

In addition to established gastrointestinal hormones--secretin, cholecystokinin-pancreozymin (CCK-PZ), gastrin, and glucagon---some 30 polypeptides with gastrointestinal actions can be listed. New aspects of these substances include the following: Gastrin and vasoactive intestinal peptide (VIP) can be also encountered in the central nervous system and may act as transmitters. CCK-PZ-serum concentrations are found markedly elevated in patients with exocrine pancreatic insufficiency; this may provide the opportunity to establish a realtively simple screening test...

1. The insulinogenic factor of the gastrointestinal mucosa named "incretin" is only one part of the complex enteroinsular axis. --2. Of the chemically defined gastrointestinal hormones GIP is the strongest incretin candidate. --3. Because of the dual function of GIP as gastrone and insulinotropic substance several safeguards against GIP-mediated insulin hypoglycaemia exist. --4. No pathological condition has yet been found which is causally related to hyper- or hyposecretion of GIP. However, an exaggerated GIP response (usually secondary to the disease) may participate in the pathogenesis of hyperinsulinaemia of patients with obesity and duodenal ulcer...