The effects of gastrin, gastric inhibitory polypeptide, secretin, and the octapeptide of cholecystokinin upon immunoreactive somatostatin release by the perfused canine pancreas.

Ipp, Eli; Dobbs, R. E.; Harris, V.; Arimura, Akira; Vale, Wylie; Unger, Roger H

doi:10.1172/jci108875

Cited by 114 publications

(37 citation statements)

References 25 publications

(25 reference statements)

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“…By definition, incretin hormones are released in response to nutrient ingestion and stimulate pancreatic ␤-cells at their typical postprandial concentrations, especially in the presence of elevated plasma glucose concentrations (2,21). Such properties have been ascribed to GIP (22)(23)(24) and cholecystokinin (shown only in dogs and rodents) (25,26). According to this strict definition, GLP-1 would apparently not fulfill the criteria for an incretin hormone in the setting of the present experiments because it reduced rather than stimulated postprandial insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

Erythromycin Antagonizes the Deceleration of Gastric Emptying by Glucagon-Like Peptide 1 and Unmasks Its Insulinotropic Effect in Healthy Subjects

et al. 2005

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Glucagon-like peptide 1 (GLP-1) has been proposed to act as an incretin hormone due to its ability to enhance glucose-stimulated insulin secretion. Because GLP-1 also decelerates gastric emptying, it physiologically reduces rather than augments postprandial insulin secretory responses. Therefore, we aimed to antagonize the deceleration of gastric emptying by GLP-1 to study its effects on insulin secretion after a meal. Nine healthy male volunteers (age 25 ؎ 4 years, BMI 25.0 ؎ 4.9 kg/m 2 ) were studied with an infusion of GLP-1 (0.8 pmol ⅐ kg ؊1 ⅐ min ؊1 from ؊30 to 240 min) or placebo. On separate occasions, the prokinetic drugs metoclopramide (10 mg), domperidone (10 mg), cisapride (10 mg, all at ؊30 min per oral), or erythromycin (200 mg intravenously from ؊30 to ؊15 min) were administered in addition to GLP-1. A liquid test meal (50 g sucrose and 8% mixed amino acids in 400 ml) was administered at 0 min. Capillary and venous blood samples were drawn for the determination of glucose (glucose oxidase), insulin, C-peptide, GLP-1, glucagon, gastric inhibitory polypeptide (GIP), and pancreatic polypeptide (specific immunoassays). Gastric emptying was assessed by the phenol red dilution technique. Statistical analyses were performed using repeated-measures ANOVA and Duncan's post hoc test. GLP-1 significantly decelerated the velocity of gastric emptying (P < 0.001). This was completely counterbalanced by erythromycin, whereas the other prokinetic drugs used had no effect. Postprandial glucose concentrations were lowered by GLP-1 (P < 0.001 vs. placebo), but this effect was partially reversed by erythromycin (P < 0.05). Insulin secretory responses to the meal were lower during GLP-1 administration (P < 0.05 vs. placebo). However, when erythromycin was added to GLP-1, insulin concentrations were similar to those in placebo experiments. The suppression of meal-related increments in glucagon secretion by GLP-1 was reversed by erythromycin (P < 0.001). The time course of GIP secretion was delayed during GLP-1 administration (P < 0.05), but when erythromycin was added, the pattern was similar to placebo experiments. GLP-1 administration led to a reduction in pancreatic polypeptide plasma concentrations (P < 0.05). In contrast, pancreatic polypeptide levels were markedly increased by erythromycin (P < 0.001). Intravenous erythromycin counteracts the deceleration of gastric emptying caused by GLP-1, probably by interacting with the parasympathetic nervous system (pancreatic polypeptide responses). Despite augmented rises in insulin secretion, the glucose-lowering effect of GLP-1 is markedly reduced when the deceleration of gastric emptying is antagonized, illustrating the importance of this facet of the multiple antidiabetic actions of GLP-1. Diabetes 54: 2212-2218, 2005 I nsulin secretion after meal ingestion is stimulated not only by the rise in glycemia, but also by the secretion of peptide hormones ("incretins") from the gut (1,2). The postprandial enhancement of insulin secretion by gut-derived factors is called the ...

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Section: Discussionmentioning

confidence: 99%

Erythromycin Antagonizes the Deceleration of Gastric Emptying by Glucagon-Like Peptide 1 and Unmasks Its Insulinotropic Effect in Healthy Subjects

et al. 2005

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“…In addition, we wished to investigate how blocking of delta cell action might influence the effect of GIP and glucose on glucagon secretion, given the fact that GIP and glucose, like GLP-1, have been reported to stimulate pancreatic somatostatin secretion [28][29][30][31][32]. As a model, we used the isolated perfused rat pancreas, in which the integrity of the islet's cytoarchitecture and microvasculature is preserved, which is crucial when investigating paracrine interactions between islet cells.…”

Section: Introductionmentioning

confidence: 99%

Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas

et al. 2008

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Aims/hypothesis The glucose-lowering effect of glucagonlike peptide-1 (GLP-1) is based not only upon its potent insulinotropic actions but also on its ability to restrain glucagon secretion. Surprisingly, the closely related glucose-dependent insulinotropic peptide (GIP) stimulates glucagon release. We examined whether the islet hormone somatostatin, which strongly inhibits glucagon secretion, is involved in this divergent behaviour. Methods At 1.5 mmol/l glucose and therefore minimal insulin secretion, the glucagon, insulin and somatostatin responses to 20 mmol/l glucose, GLP-1, GIP and somatostatin were studied in the presence of a high-affinity monoclonal somatostatin antibody and of a highly specific somatostatin receptor subtype 2 (SSTR2) antagonist (PRL-2903) in the isolated perfused rat pancreas. Results In control experiments, GLP-1 at 1 and 10 nmol/l reduced glucagon secretion significantly to 59.0±6.3% (p<0.004; n=5; SSTR2 series; each vs pre-infusion level) and to 48.0±2.6% (p<0.001; n=6; somatostatin antibody series) respectively. During somatostatin antibody administration, GLP-1 still inhibited glucagon secretion significantly, but the effect was less pronounced than in control experiments (p<0.018). Co-infusion of the SSTR2 antagonist completely abolished the GLP-1-induced suppression of glucagon secretion. In contrast, neither the GIP-induced stimulation of glucagon release nor its inhibition by 20 mmol/l glucose was altered by somatostatin antibody or SSTR2 antagonist administration. Conclusions/interpretationWe conclude that GLP-1 is capable of inhibiting glucagon secretion even in the absence of secretory products from the beta cell. It is highly likely that this is mediated via somatostatin interacting with SSTR2 on rat alpha cells. In contrast, GIP and glucose seem to influence the alpha cell independently of somatostatin secretion.

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“…And in a Starling Review, it is only fitting to mention that secretin was shown to be a powerful stimulator of the secretion of pancreatic somatostatin in a perfused dog pancreas preparation (Ipp et al 1977).…”

Section: Somatostatinmentioning

confidence: 99%

Hypothalamic hormones a.k.a. hypothalamic releasing factors

Guillemin¹

2005

Journal of Endocrinology

111

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Originally searched for and eventually isolated as factors of hypothalamic origin controlling anterior pituitary secretions, these hypophysiotropic peptides are now a chapter of physiology and medical endocrinology of their own. Defying the concept of 'neuropeptides' they and their receptors are now known to be ubiquitous and to have subtle as well as profound effects on a large number of functions of both soma and psyche. This review will be composed of brief essays on current knowledge of each of the original 'hypothalamic hormones', TRH, GnRH, somatostatin, GHRH and corticotropin releasing hormone and will close on possible and probable futures.

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The effects of gastrin, gastric inhibitory polypeptide, secretin, and the octapeptide of cholecystokinin upon immunoreactive somatostatin release by the perfused canine pancreas.

Cited by 114 publications

References 25 publications

Erythromycin Antagonizes the Deceleration of Gastric Emptying by Glucagon-Like Peptide 1 and Unmasks Its Insulinotropic Effect in Healthy Subjects

Erythromycin Antagonizes the Deceleration of Gastric Emptying by Glucagon-Like Peptide 1 and Unmasks Its Insulinotropic Effect in Healthy Subjects

Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas

Hypothalamic hormones a.k.a. hypothalamic releasing factors

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